2018 Scientific Report

Van Andel Research Institute 

Scientific Report 2018

Cover image: The yeast Mcm2-7 double hexamer, the core of the 

DNA replication helicase. A complete view of this cryo-EM structure is 

found on p. 35.


Scientific Report 2018 

VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT | i

Published March 2018. 

Copyright 2018 by Van Andel Institute: all rights reserved. 

Van Andel Institute, 333 Bostwick Avenue, N.E. 

Grand Rapids, Michigan 49503, U.S.A. 

ii | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

In Memoriam 

Arthur S. Alberts, Ph.D. 

1964–2016 

Art Alberts passed away in December 2016 after a 

courageous eight-year battle with brain cancer. He 

was a passionate, deeply inquisitive scientist who 

joined VARI in 2000 as one of its first scientific 

investigators. Art was brought up in Southern 

California, but he never seemed to allow Michigan 

winters to intimidate him into forgoing flip-flops 

and shorts. He was a friend, mentor, and 

collaborator, a man who loved the purity of science, 

the thrills of a dangerous mountain bike trail, and a 

good IPA. He is deeply missed. 

VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT | iii

Table of Contents 

2017 At-A-Glance vi 

Introduction 1 

Center for Cancer and Cell Biology 4 

JUAN DU, Ph.D. 6 

PATRICK J. GROHAR, M.D., Ph.D. 7 

BRIAN B. HAAB, Ph.D. 8 

XIAOHONG LI, Ph.D. 9 

WEI LÜ, Ph.D. 10 

KARSTEN MELCHER, Ph.D. 11 

LORENZO F. SEMPERE, Ph.D. 12 

MATTHEW STEENSMA, M.D. 13 

BART O. WILLIAMS, Ph.D. 14 

NING WU, Ph.D. 15 

H. ERIC XU, Ph.D. 16 

TAO YANG, Ph.D. 17 

Center for Epigenetics 20 

STEPHEN B. BAYLIN, M.D. 22 

PETER A. JONES, Ph.D., D.Sc. 23 

STEFAN JOVINGE, M.D., Ph.D. 24 

PETER W. LAIRD, Ph.D. 25 

HUILIN LI, Ph.D. 26 

GERD PFEIFER, Ph.D. 27 

SCOTT ROTHBART, Ph.D. 28 

HUI SHEN, Ph.D. 29 

PIROSKA E. SZABÓ, Ph.D. 30 

TIMOTHY J. TRICHE, JR., Ph.D. 31 

STEVEN J. TRIEZENBERG, Ph.D. 32 

iv | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

Center for Neurodegenerative Science 36 

LENA BRUNDIN, M.D., Ph.D. 38 

PATRIK BRUNDIN, M.D., Ph.D. 39 

GERHARD (Gerry) A. COETZEE, Ph.D. 40 

JEFFREY H. KORDOWER, Ph.D. 41 

VIVIANE LABRIE, Ph.D. 42 

JIYAN MA, Ph.D. 43 

DARREN J. MOORE, Ph.D. 44 

Educational and Training Programs 62 

VAIGS GRADUATE STUDENTS 64 

SUMMER INTERNSHIP PROGRAM 65 

POSTDOCTORAL FELLOWSHIP PROGRAM 66 

Organization 68 

MANAGEMENT 70 

ADMINISTRATIVE DEPARTMENTS 72 

ORGANIZATIONAL CHART 74 

Core Technologies and Services 48 

MARIE ADAMS, M.S. 50 

Genomics 

MEGAN BOWMAN, Ph.D. 51 

Bioinformatics and Biostatistics 

BRYN EAGLESON, M.S., LATG 52 

Vivarium and Transgenics 

CORINNE ESQUIBEL, Ph.D. 53 

Confocal Microscopy and 

Quantitative Imaging 

SCOTT D. JEWELL, Ph.D. 54 

Pathology and Biorepository 

RACHAEL SHERIDAN, Ph.D. 55 

Flow Cytometry 

GONGPU ZHAO, Ph.D. 56 

Cryo-Electron Microscopy 

Awards for Scientific Achievement 58 

JAY VAN ANDEL AWARD FOR OUTSTANDING 59 

ACHIEVEMENT IN PARKINSON’S 

DISEASE RESEARCH 

HAN-MO KOO MEMORIAL AWARD 60 

TOM ISAACS AWARD 61 

VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT |v

2017 At-A-Glance 

Record-breaking funding 

115 total active awards totaling $97 million 

32 new awards in 2017 totaling $33 million 

Of those, 13 awards, for $25 million, 

are federal grants 

A growing scientific impact 

145 2017 publications, 

132 peer-reviewed 

Prestigious faculty 

In 2017, the Institute celebrated Chief Scientific Officer Dr. Peter Jones’s election to the American 

Academy of Arts and Sciences, placing him in the elite company of more than 250 Nobel Laureates 

and 60 Pulitzer Prize winners. Director’s Scholar Dr. Stephen Baylin also earned the honor of being 

elected to the National Academy of Sciences, an independent and nonpartisan advisor to the 

federal government on matters related to science and technology. In all, VARI is home to 

2 fellows of the American Academy of Arts & Sciences 

2 members of the National Academy of Sciences 

3 fellows of the American Association for the Advancement of Science 

3 fellows of the American Association for Cancer Research Academy 

A collaborative effort 

383 collaborating organizations 

32 countries in which 

VARI collaborates 

A growing team 

384 total employees 

223 total research employees 

31 faculty 

43 postdoctoral fellows 

27 Van Andel Institute Graduate School Ph.D. students 

vi | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

Introduction 

In many ways, 2017 was a record-breaking year for Van Andel Research 

We continue to build critical 

mass, thanks to an ambitious 

recruiting effort conducted 

in accordance with our 

Strategic Plan. 

Institute. We experienced incredible growth in all aspects of our 

scientific enterprise, from an all-time high in scientific publications to 

an incredible increase in peer-reviewed federal funding, the most ever 

awarded in our 21-year history. Several new faculty have arrived and 

more will be joining us soon, which will bolster our existing research 

programs and support the establishment of new ones. And, we continue 

our collaborations with other leading institutions both in the U.S.A. and 

abroad to translate lab discoveries into the clinic. 

STRATEGIC GROWTH 

We continue to build critical mass, thanks to an ambitious recruiting effort 

conducted in accordance with our Strategic Plan. The Center for Cancer and Cell 

Biology added two new faculty in 2017, Wei Lü in March and Juan Du in October. 

The Lü lab uses single-particle cryo-electron microscopy and other methods to 

study the structures and mechanisms of ion channels and transmembrane receptors. 

The Du lab focuses on excitatory neuronal receptors, studying their structure and 

function via cryo-EM, electrophysiology, and X-ray crystallography. The Center for 

Neurodegenerative Science welcomed Wouter Peelaerts, who joined Patrik Brundin’s 

lab in 2017, becoming the first Fulbright Scholar to join the Institute. 

In September 2017, the Center for Epigenetics welcomed Timothy J. Triche, Jr., 

whose lab develops statistical and mathematical methods to better understand 

pediatric and adult cancers, with a special focus on cancers of the blood in children. 

We look forward to the arrival of two more faculty in early 2018—Drs. Xiaobing Shi 

and Hong Wen, both experts in cancer epigenetics. 

A major milestone was the establishment of the Institute’s David Van Andel 

Advanced Cryo-Electron Microscopy Suite in early 2017. This state-of-the-art 

facility places VARI in elite company: the suite’s most powerful microscope, the 

Titan Krios, is one of fewer than 120 in the world and can visualize structures down 

to the atomic level. The investment, made possible by CEO David Van Andel, is 

already bearing fruit. Two new structures that were solved using its instruments 

were published in the last quarter of 2017. Huilin Li’s lab and collaborators published 

the paper “Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a 

lagging-strand DNA extrusion model” in the Proceedings of the National Academy of 

Sciences USA, and Wei Lü’s lab published “Electron cryo-microscopy structure of a 

human TRPM4 channel” in Nature. These were among the 132 peer-reviewed articles 

from VARI in 2017, a new annual high for the Institute. Selected publications are 

listed for each Center and the Cores. 

VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT | 1

Introduction (cont.) 

Grant funding hit an 

all-time high in 2017 with 32 

new awards totaling over 

$33 million. 

FUNDING GROWTH 

Our growth also is reflected in grant funding, which hit an all-time high in 2017 

with 32 new awards totaling over $33 million. Of these, 13 were peer-reviewed 

federal awards accounting for over $25 million. These funds will support a plethora 

of basic and translational research endeavors aimed at making life-changing 

advances. Of note, VARI had the second highest growth in grant funding over 2016- 

2017 among 72 comparable independent research institutes. 

On the clinical front, we are thrilled that Van Andel Research Institute–Stand Up 

To Cancer Epigenetics Dream Team scientists received two of the ten inaugural 

SU2C Catalyst awards, which pair Dream Teams with industry support. Totaling 

nearly $5.5 million, these funds will fuel new, collaborative clinical trials designed 

to evaluate powerful epigenetic and immunotherapy drug combinations as potential 

cancer treatments. One grant is funded by Merck & Co. against non-small-cell lung 

cancer, one of the most common and deadly types of cancer, and the second is 

funded by Genentech against bladder cancer, a disease that claims thousands of lives 

annually. 

Among the major National Institutes of Health awards were a seven-year R35/ 

Outstanding Investigator Award from NIH/NCI to Peter Jones; to Patrik Brundin, an 

R01 from NIH/NIDCD, an R21 from NIH/NINDS, and a Department of Defense award; 

to Scott Rothbart, an R35/Maximizing Investigators’ Research Award from NIH/ 

NIGMS; to Peter Laird, an R01 from NIH/NCI; to Darren Moore, an R01 from NIH/ 

NINDS; to Ning Wu, an R01 from NIH/NCI; to Huilin Li, an R01 from NIH/NIGMS; 

and to Jiyan Ma, an R21 from NIH/NINDS. 

Several of VARI’s postdoctoral fellows and graduate students also received funding 

in 2017. Xi Chen, of the Moore laboratory, now has a fellowship from the Parkinson’s 

Foundation supporting her studies into a new model for familial Parkinson’s disease. 

An Phu Tran Nguyen and Md Shariful Islam, also in the Moore Lab, received grants 

from the American Parkinson’s Disease Association. VARI Fellow Xiaotian Zhang 

was the recipient of an American Society of Hematology Fellow Scholar Award in 

basic and translational research—the first ASH fellowship to a VARI scientist—and 

Rochelle Tiedemann, of the Jones and Rothbart labs, received the Institute’s first 

American Cancer Society fellowship. 

Nicole Vander Schaaf, a graduate student in the Laird lab, received an F31 

predoctoral training fellowship from the National Institutes of Health for 

her project, “The role of polycomb target gene DNA methylation in intestinal 

tumorigenesis.” F31 grants are highly competitive fellowships that support 

promising graduate students as they work on their dissertations. Nicole is our first 

graduate student to be awarded an F31. 

2 | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT

By harnessing new knowledge 

born out of revolutionary 

scientific innovation and 

technology and working 

together against disease, we 

can—and will—change human 

health for the better. 

AWARDS AND SYMPOSIA 

VARI’s Chief Scientific Officer Peter Jones was elected to the American Academy of 

Arts and Sciences in April, and Stephen Baylin was elected to the National Academy 

of Sciences in May. Congratulations to both! 

In May, the Institute presented U.S. Rep. Fred Upton with a Legislative Champion 

Award on behalf of the Association for Independent Research Institutes (AIRI). 

Upton, along with U.S. Rep. Diana DeGette, spearheaded the 21 st Century Cures Act, 

which passed with bipartisan support and infused more than $6 billion in new 

funding to the National Institutes of Health. 

VARI hosted several scientific symposia in 2017. Among those events were 

“Osteoporosis: An Impending Public Health Crisis”; “New Frontiers in Cancer 

Metabolism”; “Frontiers in Reproductive Epigenetics”; “Origins of Cancer”; “A 

Celebration of the Cryo-EM Revolution"; and “Grand Challenges in Parkinson’s 

Disease” and its parallel patient meeting, “Rallying to the Challenge”. We also held 

the second “Epigenomics at VARI” graduate student workshop during the summer. 

A BRIGHT TOMORROW 

As we move into the future, we do so with a renewed commitment to improving 

human health through rigorous science. This mission is an urgent one: as the 

world’s population continues to grow and age, the incidence of cancer and 

neurodegenerative diseases also are slated to rise. Improved preventative strategies, 

diagnostic techniques, treatments, and—ultimately—cures are desperately needed 

for the millions around the world who face these diseases today or who will face 

them tomorrow. 

The past decade has encompassed a scientific renaissance of sorts, one that can be 

seen in research organizations around the world, including VARI. By harnessing 

new knowledge born out of revolutionary scientific innovation and technology and 

working together against disease, we can—and will—change human health for the 

better. 


Center for Cancer and Cell Biology 

Bart O. Williams, Ph.D. 

Director 

The Center’s scientists 

study the basic 

mechanisms and 

molecular biology 

of cancer and other 

diseases, with the goal 

of developing better 

diagnostics and therapies. 


A depiction of arrestin binding by a phosphorylated and active rhodopsin. The cell membrane 

lipids are shown as cream colored, rhodopsin is blue, and arrestin is red. The phosphorylated 

C-terminal tail of rhodopsin binds to the N-domain (left) of the arrestin molecule. In the main contact 

region between the two molecules (central), arrestin accommodates the ICL2 helix of rhodopsin. In 

this fully activated state, the tip of arrestin’s C-domain contacts the membrane (right). 

Image by Parker de Waal of the Xu lab.


JUAN DU, Ph.D. 

Dr. Du earned her Ph.D. at the University of Freiburg. She joined the VARI 

faculty in October 2017 as an Assistant Professor. 

RESEARCH INTERESTS 

The lab is focused on understanding the mechanism and pharmacology of excitatory 

neuronal receptors, which are crucially involved in numerous neurological diseases. 

A combined approach of single-particle cryo-EM, patch-clamp electrophysiology, 

and X-ray crystallography is employed to study the atomic structures and biological 

functions of these ion channel receptors. 

STAFF 

Chen Fan, Ph.D. 

Michelle Martin, A.A. 


PATRICK J. GROHAR, M.D., Ph.D. 

Dr. Grohar earned his Ph.D. in chemistry and his M.D. from Wayne State 

University. He joined VARI in 2015 as an Associate Professor, and he has 

clinical and research responsibilities at Spectrum Health and Michigan 

State University, respectively. 


Our laboratory studies pediatric sarcomas, and our goal is to develop novel, 

molecularly targeted therapies and to translate those therapies into the clinic. 

Most pediatric sarcomas are characterized by oncogenic transcription factors that 

are required for cell survival. We are developing new approaches to target those 

molecules. 

STAFF 

Elissa Boguslawski, R.L.A.T. 

Jenna Gedminas, M.D. 

Susan Goosen, B.S., M.B.A. 

Mitchell McBrairty, B.S. 

Michelle Minard, B.S. 

Brandon Oswald, B.S. 

Erik Peterson, B.S., M.S. 

Katie Sorensen, B.S. 

STUDENTS 

Maggie Chasse, M.S. 

Guillermo Flores, B.S. 

Trabectedin is a natural product originally isolated from the sea squirt, Ecteinascidia 

turbinata. Our recent work has focused on characterizing the mechanism of 

trabectedin’s suppression of the EWS-FLI1 transcription factor in Ewing sarcoma, 

identifying second-generation trabectedin analogs, and developing new combination 

therapies. We showed that the drug works by redistributing EWS-FLI1 within the 

nucleus to the nucleolus. This mechanism provides justification for using a secondgeneration 

compound, lurbinectedin, which maintains the nuclear redistribution of 

EWS-FLI1 but accumulates to higher serum concentrations. 

Over the past year, we have shown convincingly that a targeted combination therapy 

of trabectedin plus irinotecan provides cooperative suppression of EWS-FLI1. 

Irinotecan augments and sustains suppression of EWS-FLI1 in vivo, leading to the 

differentiation of Ewing sarcoma cells into benign tissue. We have also shown that 

lurbinectedin maintains both this synergy with irinotecan and the mechanism of 

synergy. We have a number of anecdotal responses to treatment with trabectedin 

plus irinotecan, and responses to lurbinectedin have been seen in patients in two 

independent studies. We are working to formally evaluate these combinations in 

phase II studies in the United States. 

We have also extensively studied mithramycin, which reverses EWS-FLI1 activity 

and blocks the expression of key EWS-FLI1 downstream targets. In a phase I/II trial 

at the National Cancer Institute, we found that mithramycin did not achieve serum 

levels high enough to block EWS-FLI1 activity. We have now identified secondgeneration 

compounds with improved properties that show excellent activity in 

Ewing sarcoma cells. We are extending these findings to other tumor types. We have 

shown that cells deficient in components of the SWI/SNF chromatin remodeling 

complex are hypersensitive to mithramycin. Work is in progress to understand 

the mechanism of this hypersensitivity. We are also exploring the interface of 

epigenetics and transcription as a drug target. 



BRIAN B. HAAB, Ph.D. 

Dr. Haab obtained his Ph.D. in chemistry from the University of 

California at Berkeley in 1998. He joined VARI as a Special Program 

Investigator in 2000, became a Scientific Investigator in 2004, and is 

now a Professor. 

STAFF 

ChongFeng Gao, Ph.D. 

Zachary Klamer, B.S. 

Ying Liu, Ph.D. 

Katie Partyka, B.S. 

Ben Staal, M.S. 

Jeanie Wedberg, A.S. 

Luke Wisniewski, B.S. 

STUDENTS 


Patients facing a possible diagnosis of cancer need answers to such fundamental 

questions as whether a lesion is cancerous and, if so, which treatment will work 

best, yet getting the answers can be difficult. The heterogeneity of cancers of a 

particular organ is a major source of the difficulty. For example, for pancreatic 

cancer, physicians do not have tests that reliably distinguish cancerous from noncancerous 

lesions or that group the cancers into specific subtypes. To address this 

need, we are 1) seeking molecular markers to identify the subtypes of pancreatic 

cancer cells; 2) determining the behavioral and biological differences between 

the subtypes; and 3) developing assays to detect the subtypes in a clinical setting. 

With such assays, we hope to improve the ability to detect and diagnose pancreatic 

cancers, to enable prediction of the behavior of each cancer, and to guide studies 

aimed at treating each subtype. 

We found that a carbohydrate structure, which we named the sTRA antigen, is 

produced by a subtype of pancreatic cancer cell that is different from typical 

cancer cells. We also found that another carbohydrate, the well-known CA19-9 

antigen, identifies a separate type of pancreatic cancer cell. Individual tumors may 

have cancer cells producing one, both, or neither of the antigens. Our research is 

revealing that the sTRA-producing cancer cells are more resistant to death and 

more aggressive than the CA19-9-producing cells. We are seeking to clarify the 

nature and mechanisms of the differences between the subtypes and to determine 

optimal treatments for each. Both antigens are secreted into the blood, so we are 

investigating the use of blood tests for sTRA and CA19-9 to identify more pancreatic 

cancers than previously possible and to determine their subtype. We are also using 

new methods of carbohydrate analysis developed in our lab to find markers for 

additional subtypes of pancreatic cancer cells. 

David Ayala-Talavera 

Daniel Barnett, B.A., B.S. 

Anna Barry, B.S. 

Johnathan Hall 

Peter Hsueh, B.S. 

Hannah Kalee 


XIAOHONG LI, Ph.D. 

Dr. Li received her Ph.D. from the Institute of Zoology, Chinese Academy of 

Sciences, in Beijing in 2001. She joined VARI as an Assistant Professor 

in September 2012. 


Our laboratory is committed to understanding tumor dormancy and cancer bone 

metastasis. Our long-term goals are to develop better therapeutic approaches for 

bone metastasis and to prolong a dormancy-permissive bone microenvironment so 

that cancer cells can be killed while they are in that state. 

STAFF 

Sourik Ganguly, Ph.D. 

Alexandra Vander Ark, M.S. 


Erica Woodford, B.S. 

Project 1. Influence of the bone microenvironment on drug resistance in prostate 

cancer bone metastasis. Second-line hormonal therapies such as enzalutamide 

improve overall patient survival by only a few months in about 50% of patients, 

and almost all patients develop drug resistance. Thus, we need to determine the 

mechanisms of drug resistance and to develop new approaches for overcoming it. 

Based on our studies, the goals of this project are to determine how enzalutamide 

decreases TGFBR2 in osteoblasts, to investigate how loss of TGFBR2 in osteoblasts 

promotes the progression of prostate cancer bone metastases, and to target the 

underlying mechanism as a novel therapeutic approach to overcoming enzalutamide 

resistance. 

Project 2. Influence of the bone microenvironment on prostate cancer dormancy. 

The majority of cancer patients die of metastases that begin years or decades after 

primary diagnosis and treatment. Up to 70% of prostate cancer patients have 

disseminated tumor cells in the bone marrow at the time of initial diagnosis, and 

these cells can remain dormant and reactivate later. Understanding the underlying 

mechanism will provide novel avenues for early preventive and therapeutic 

approaches to eradicating metastatic recurrence. We have created a mouse model in 

which prostate cancer bone metastasis development is delayed by four weeks, which 

is equivalent to three years in humans. Based on our studies, we are proposing to 

test the effect of blocking CTHRC1 or of vitamin C treatment on prostate cancer 

dormancy and bone metastasis. 



WEI LÜ, Ph.D. 

Wei Lü earned his Ph.D. from the University of Freiburg in the laboratory 

of Oliver Einsle. He then was a postoctoral fellow in the laboratory of Eric 

Gouaux (HHMI/Vollum Institute) before joining VARI as an 

Assistant Professor in 2017. 


We use single-particle cryo-electron microscopy and other biophysical/biochemical 

methods to study the structure and mechanism of ion channels and transmembrane 

receptors that are linked to neurological diseases and cancers. We recently 

determined the cryo-EM structure of the human TRPM4 channel. 

STAFF 

Yihe Huang, Ph.D. 


Paige Winkler, Ph.D. 

STUDENT 

Wooyoung Choi 


KARSTEN MELCHER, Ph.D. 

Dr. Melcher earned his master's degree in biology and his Ph.D. in 

biochemistry from the Eberhard Karls Universität in Tübingen, Germany. 

He was recruited to VARI in 2007, and in 2013 he was promoted to 

Associate Professor. 


Our laboratory studies the structure and function of proteins that have central 

roles in cellular signaling. To do so, we employ X-ray crystallography and cryoelectron 

microscopy in combination with biochemical and cellular methods to 

identify mechanisms of signaling and frameworks for the rational design of new 

and improved drugs against diseases such as cancer, diabetes, and neurological 

disorders. 

STAFF 

Xin Gu, M.S. 


STUDENTS 

Zachary DeBruine, B.S. 

Yan Yan, B.S. 

VISITING SCIENTIST 

Feng Zhang, Ph.D. 

AMP-activated protein kinase (AMPK) 

AMPK is a central regulator of energy homeostasis and important drug target for 

the treatment of metabolic diseases, including diabetes, obesity, and cancer. AMPK 

senses the energy state of the cell by competitive binding of AMP, ADP, and ATP to 

three sites in its γ subunit. We are determining the structural mechanisms of AMPK 

regulation by direct binding of AMP, ADP, ATP, and various drugs, as well as by 

post-translational modifications. 

Plant hormone signaling 

We are studying perception, signal transduction, and target gene regulation for 

hormones that reprogram plants in response to drought and other abiotic stresses 

(abscisic acid), to herbivorous insects and microbial pathogens (jasmonates), and to 

mineral nutrient stresses (strigolactones). These stresses are responsible for major 

crop losses worldwide and have a large impact on human malnutrition. 

WNT reception and signaling 

WNTs are morphogens that have key roles in human development and stem cell 

maintenance; components of the WNT signaling pathway are frequently mutated 

in cancers, as well as in bone and retinal diseases. This pathway is therefore an 

important therapeutic target. Yet, how to therapeutically target the docking of a 

WNT to its cell surface receptor complex, and the molecular mechanism of how such 

docking transduces signals to the inside of the cell, have remained elusive. We are 

using a combination of structural and live-cell analysis to determine the structure of 

the intact receptor complex and the mechanism of WNT transmembrane signaling. 



LORENZO F. SEMPERE, Ph.D. 

Dr. Sempere obtained his B.S. in biochemistry at Universidad Miguel 

Hernández, Elche, Spain, and earned his Ph.D. at Dartmouth under Victor 

Ambros. He joined VARI in January 2014 as an Assistant Professor. 

STAFF 

Josh Schipper, Ph.D. 


Jenni Westerhuis, M.S.Ed., M.S. 

STUDENTS 

Sudakshina Chakrabarty 

Joyce Goodluck 


Our laboratory pursues complementary lines of translational research to explain the 

etiological role of microRNAs and to unravel microRNA regulatory networks during 

carcinogenesis. We investigate these questions in clinical samples and preclinical 

models of breast cancer and pancreatic cancer. MicroRNAs can regulate and 

modulate the expression of hundreds of target genes, some of which are components 

of the same signaling pathways or biological processes. Thus, functional modulation 

of a single microRNA can affect multiple target mRNAs (i.e., one drug, multiple hits), 

unlike therapies based on small interfering RNAs, antibodies, or small-molecule 

inhibitors. The laboratory has active projects in the areas of cancer biology and 

tumor microenvironment, with a translational focus toward improving diagnostic 

applications and therapeutic strategies. 

Because tissue samples are the direct connection between cancer research and 

cancer medicine, detailed molecular and cellular characterization of tumors provides 

the opportunity to translate scientific knowledge into useful clinical information. We 

use innovative multiplexed immunohistochemical and in situ hybridization assays 

to implement diagnostic applications of microRNA biomarkers. Molecular biology 

and cell biology studies help to identify microRNA targets and regulatory networks. 

Recent projects include the following. 

• Clinically validating tumor compartment-specific expression of miR-21 as a 

prognostic marker for breast cancer. There is focused interest in the stromal 

expression of miR-21 in triple-negative breast cancer, for which prognostic 

markers and effective targeted therapies are lacking. 

• Developing integrative diagnostics for pancreatic cancer using information from 

cancer-associated microRNAs and protein glycosylation. Integrative marker 

analysis should enhance diagnostic power and interpretation. 

• Developing methods for isolating microRNA/target mRNA interactions in in vitro 

and in vivo systems. 

• Evaluating the miR-21 activity required in cancer cell and tumor stromal 

compartments to support aggressive and metastatic features in animal models 

of breast and pancreatic cancer. 


MATTHEW STEENSMA, M.D. 

Dr. Steensma received his B.A. from Hope College and his M.D. from Wayne 

State University School of Medicine in Detroit. He is a practicing surgeon 

in the Spectrum Health Medical Group, and he joined VARI as an 

Assistant Professor in 2010. 

STAFF 

Patrick Dischinger, B.S., MB(ASCP) CM 

Curt Essenburg, B.S., LATG 

Carrie Graveel, Ph.D. 


Elizabeth Tovar, Ph.D. 


Our laboratory conducts research into new treatment strategies for sarcomas. 

Specifically, we are interested in determining the mechanisms underlying tumor 

formation in sporadic bone and soft-tissue sarcomas and in neurofibromatosis 

type 1, a hereditary disorder caused by mutations in the neurofibromin 1 (NF1) 

gene. Neurofibromin is considered a tumor suppressor that suppresses Ras 

activity by promoting Ras GTP hydrolysis to GDP. People with mutations in the 

NF1 gene develop benign tumors called neurofibromas and have an elevated risk 

of malignancies ranging from solid tumors (including sarcomas) to leukemia. The 

disease affects 1 in 3000 people in the United States, of whom 8–13% will ultimately 

develop a neurofibromatosis-related sarcoma in their lifetime. These aggressive 

tumors typically arise from benign neurofibromas, but the process of benign-tomalignant 

transformation is not well understood, and treatment options are limited, 

leading to poor five-year survival rates. 

Our current research efforts include the development of genetically engineered 

mouse models of neurofibromatosis type 1 tumor progression, most notably NF1- 

related MPNSTs and breast cancer; the identification of targetable patterns of 

intratumoral and intertumoral heterogeneity through next-generation sequencing; 

genotype–phenotype correlations in neurofibromatosis type 1 and related diseases; 

and mechanisms of chemotherapy resistance in bone and soft-tissue sarcomas. 

STUDENTS 

Eve Gardner 

Jamie Grit, B.S. 

Candace King, M.A. 

Courtney Schmidt 



BART O. WILLIAMS, Ph.D. 

Dr. Williams received his Ph.D. in biology from Massachusetts Institute 

of Technology in 1996, where he trained with Tyler Jacks. Following 

postdoctoral study with Harold Varmus, he joined VARI in July 1999. He is 

now a Professor and the Director of the Center for Cancer and Cell Biology. 

STAFF 

Cassie Diegel, B.S. 

Gabrielle Foxa, B.S. 

Mitch McDonald, B.S. 

Megan Michalski, D.D.S, Ph.D. 


Alex Zhong, Ph.D. 

STUDENTS 

Isaac Izaguirre 

Katie Krajnak, M.S. 

Adam Racette 


We are studying how alterations in the WNT signaling pathway cause human 

disease. Given that WNT signaling functions in the growth and differentiation 

of most tissues, it is not surprising that changes in this pathway are among the 

most common events in human cancer. Other diseases, including osteoporosis, 

cardiovascular disease, and diabetes, have also been linked to it. Our work includes 

studying the role of WNT signaling in normal bone formation and in the metastasis 

of cancer to the bone. We are also interested in identifying the genes that play key 

roles in skeletal development and maintenance of bone mass. 

Mutations in LRP5, a WNT receptor, have been causally linked to alterations in 

human bone development. We have characterized a mouse strain deficient in LRP5 

and have shown that it recapitulates the low-bone-density phenotype seen in 

human patients who have that deficiency. We have further shown that mice carrying 

mutations in both LRP5 and the related LRP6 protein have even more-severe defects 

in bone density. We are also examining the effects on normal bone development 

and homeostasis of chemical inhibitors of the enzyme Porcupine, which is required 

for the secretion and activity of all WNTs. Because such inhibitors are currently in 

human clinical trials for treatment of several tumor types, their side effects related 

to the lowering of bone mass must be evaluated. 

We are addressing the relative roles of LRP5 and LRP6 in WNT1-induced mammary 

carcinogenesis. A deficiency in LRP5 dramatically inhibits the development of 

mammary tumors, and a germline deficiency in LRP5 or LRP6 results in delayed 

mammary development. We are particularly interested in the pathways that may 

regulate the proliferation of normal mammary progenitor cells, as well as of tumorinitiating 

cells. In another project, we are studying the development of skeletal 

osteoblastic metastasis from prostate cancer and the ability of the tumor cells to 

become independent of androgen for survival. Finally, part of our work focuses 

on developing genetically engineered mouse models, for example, models of 

osteoarthritis. 

Nolan Redetzke 


NING WU, Ph.D. 

Dr. Wu received her Ph.D. from the Department of Biochemistry of the 

University of Toronto in 2002. She joined VARI in 2013 as an 

Assistant Professor. 


Many human diseases, such as diabetes, neurodegeneration, cancer, and heart 

problems, come with old age. Our laboratory studies the interface between cellular 

metabolism and signal transduction, focusing on key steps in glucose and lipid 

metabolism in order to understand the ways that nutrients can delay aging effects 

and thus postpone the onset of disease. 

STAFF 

Holly Dykstra, B.S. 

Althea Waldhart, B.S. 


Glucose is a vital, highly regulated metabolite in the human body. Its concentration 

is tightly controlled within a narrow range by factors secreted from several tissues. 

Too much glucose uptake leads to systemic problems that partly stem from oxidative 

stress generated by the mitochondria. Our lab examines the mechanism by which 

cells control glucose uptake, what regulates the flux from glucose to unwanted lipid 

accumulation, and how mitochondrial function is affected by glucose concentration. 

At the atomic scale, we employ cryo-electron microscopy to solve the structures 

of transporter proteins and their regulators. At the cellular level, we investigate 

how cells respond to metabolic stress. At the organism level, we integrate the 

cellular response with systemic response to understand how diet can modify and 

curb unwanted oxidative damage. This research will provide better insight into the 

relationship between diet and health and open the possibility of individualized diet 

recommendations to delay aging effects. 



H. ERIC XU, Ph.D. 

Dr. Xu went to Duke University and the University of Texas Southwestern 

Medical Center, earning his Ph.D. in molecular biology and biochemistry. 

He joined VARI in July 2002 and is now a Professor. Dr. Xu is also the 

Primary Investigator and Distinguished Director of the VARI–SIMM 

Research Center in Shanghai, China. 


Hormone signaling is essential to eukaryotic life. Our research focuses on the 

signaling mechanisms of physiologically important hormones, striving to answer 

fundamental questions that have a broad impact on human health and disease. 

We are studying two families of proteins, the nuclear hormone receptors and the 

G protein–coupled receptors (GPCRs), because these receptors are fundamentally 

important for treating major human diseases. 

STAFF 

Xiang Gao, Ph.D. 

Yanyong Kang, Ph.D. 


Kelly Powell, B.S. 

Xiaoyin (Edward) Zhou, Ph.D. 

STUDENTS 

Parker de Waal, B.S. 

Yan Yan, B.S. 

VISITING SCIENTIST 

Ross Reynolds, Ph.D. 

Nuclear hormone receptors 

The nuclear hormone receptors form a large family comprising ligand-regulated 

and DNA-binding transcription factors, which include receptors for the classic 

steroid hormones such as estrogen, androgens, and glucocorticoids, as well as 

receptors for peroxisome proliferator activators, vitamin D, vitamin A, and thyroid 

hormones. These receptors are among the most successful targets in the history 

of drug discovery: every receptor has one or more synthetic ligands being used 

as medicines. In the last five years, we have developed projects centering on 

the peroxisome proliferator–activated receptors (PPARα, β, and γ), the human 

glucocorticoid receptor, the androgen receptor, and a number of orphan nuclear 

receptors including CAR, SHP, SF-1, COUP-TFII, and LRH-1. We have solved many of 

their structures and identified small-molecule ligands for several of them, including 

potent ligands for GR, AR, PPARs, and COUP-TFII, which could be developed into 

therapeutics against diabetes, cancer, and inflammatory disease. 

G protein–coupled receptors 

The GPCRs form the largest family of cell-surface receptors (over 800 members) 

and account for over 40% of drug targets. There are only a few dozen solved GPCR 

structures because they are seven-transmembrane receptors. Many important 

questions regarding GPCR ligand binding and activation remain unanswered, 

including pressing questions about the assembly of GPCR signaling complexes that 

have downstream effects, such as G protein, arrestin, and GPCR kinases. Our group 

aims to use rhodopsin, the prototypical GPCR, as a model system for understanding 

how an activated GPCR is assembled with the GPCR downstream signaling effectors. 

Answering these basic questions could help in the design of pathway-selective GPCR 

ligands as drugs. 


TAO YANG, Ph.D. 

Dr. Yang received his Ph.D. in biochemistry at the Shanghai Institute of 

Biochemistry and Cell Biology, Chinese Academy of Sciences, in 2001. He 

joined VARI as an Assistant Professor in February 2013. 

STAFF 

Jianshuang Li, B.S. 


Our long-term interest is to investigate the signals and cellular processes 

orchestrating the activities of mesenchymal stem cells (MSCs) and MSC-derived 

cells during skeletal development, homeostasis, regeneration, and degeneration. 

The skeletal system develops from mesenchymal cells and is an important reservoir 

of MSCs in postnatal life. MSCs play pivotal roles in skeletal tissue growth, 

homeostasis, and repair, while dysregulations in MSC renewal, linage specification, 

and pool maintenance are common causes of skeletal disorders. Currently, our 

lab is focusing on understanding the role of the sumoylation pathway in skeletal 

degeneration, aging, and malignancy. We are also studying the role of LRP1 signaling 

in osteoporosis, inflammatory bone loss, and skeletal aging. 

Huadie Liu, M.S. 

Di Lu, M.S. 




RECENT CENTER PUBLICATIONS 

Barnett, Daniel, Ying Liu, Katie Partyka, Ying Huang, Huiyuan Tang, Galen Hostetter, Randall E. Brand, Aatur D. Singhi, Richard 

R. Drake, and Brian B. Haab. 2017. The CA19-9 and sialyl-TRA antigens define separate subpopulations of pancreatic cancer 

cells. Scientific Reports 7: 4020. 

DeBruine, Zachary J., Jiyuan Ke, Kaleeckal G. Harikumar, Xin Gu, Peter Borowsky, Bart O. Williams, Wenqing Xu, Laurence J. 

Miller, H. Eric Xu, and Karsten Melcher. 2017. Wnt5a promotes frizzled-4 signalosome assembly by stabilizing cysteine-rich 

domain dimerization. Genes and Development 31(9): 916–926. 

Droscha, Casey J., Cassandra R. Diegel, Nicole J. Ethen, Travis A. Burgers, Mitchell J. McDonald, Kevin A. Maupin, Agni S. Naidu, 

PengFei Wang, Bin T. Teh, and Bart O. Williams. 2017. Osteoblast-specific deletion of Hprt2/Cdc73 results in high bone mass 

and increased bone turnover. Bone 98: 68–78. 

Grohar, Patrick J., John Glod, Cody J. Peer, Tristan M. Sissung, Fernanda I. Arnaldez, Lauren Long, William D. Figg, Patricia 

Whitcomb, Lee J. Helman, and Brigitte C. Widemann. 2017. A phase I/II trial and pharmacokinetic study of mithramycin in 

children and adults with refractory Ewing sarcoma and EWS-FLI1 fusion transcript. Cancer Chemotherapy and Pharmacology 

80(3): 645–652. 

Grohar, Patrick J., Katherine A. Janeway, Luke D. Mase, and Joshua D. Schiffman. 2017. Advances in the treatment of pediatric 

bone sarcomas. In 2017 Educational Book, Alexandria, Virginia: American Society of Clinical Oncology. 

He, Yuanzheng, Xiang Gao, Devrishi Goswami, Li Hou, Kuntal Pal, Yanting Yin, Gongpu Zhao, Oliver P. Ernst, Patrick Griffin, 

Karsten Melcher, and H. Eric Xu. 2017. Molecular assembly of rhodopsin with G protein–coupled receptor kinases. Cell Research 

27(6): 728–747. 

Klamer, Zachary, Ben Staal, Anthony R. Prudden, Lin Liu, David F. Smith, Geert-Jan Boons, and Brian Haab. 2017. Mining highcomplexity 

motifs in glycans: a new language to uncover the fine specificities of lectins and glycosidases. Analytical Chemistry 

89(22): 12342–12350. 

Lee, Ho-Joon, Mark P. Jedrychowski, Arunachalam Vinayagam, Ning Wu, Ng Shyh-Chang, Yanhui Hu, Chua Min-Wen, Jodene 

K. Moore, John M. Asara, Costas A. Lyssiotis, Norbert Perrimon, Steven P. Gygi, Lewis C. Cantley, and Marc W. Kirschner. 2017. 

Proteomic and metabolomic characterization of a mammalian cellular transition from quiescence to proliferation. Cell Reports 

20(3): 721–736. 

Li, Jianshuang, Di Lu, Huadie Liu, Bart O. Williams, Paul A. Overbeek, Brendan Lee, Ling Zheng, and Tao Yang. 2017. Sclt1 

deficiency causes cystic kidney by activating ERK and STAT3 signaling. Human Molecular Genetics 26(15): 2949–2960. 

Ma, Honglei, Jingbo Duan, Jiyuan Ke, Yuanzheng He, Xin Gu, Ting-Hai Xu, Hong Yu, Yonghong Wang, Joseph S. Brunzelle, Yi 

Jiang, Scott B. Rothbart, H. Eric Xu, Jiayang Li, and Karsten Melcher. 2017. A D53 repression motif induces oligomerization of 

TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex. Science Advances 3(6): e1601217. 

Minciacchi, Valentina R., Cristiana Spinelli, Mariana Reis-Sobreiro, Lorenzo Cavallini, Sungyong You, Mandana Zandian, 

Xiaohong Li, Paola Chiarugi, Rosalyn M. Adam, Edwin M. Posadas, Giuseppe Viglietto, Michael R. Freeman, Emanuele Cocucci, 

Neil A. Bhowmick, and Dolores Di Vizio. 2017. MYC mediates large oncosome-induced fibroblast reprogramming in prostate 

cancer. Cancer Research 77(9): 2306–2317. 

Pridgeon, Matthew G., Patrick J. Grohar, Matthew R. Steensma, and Bart O. Williams. 2017. Wnt signaling in Ewing sarcoma, 

osteosarcoma, and malignant peripheral nerve sheath tumors. Current Osteoporosis Reports 15(4): 239–246. 

Sempere, Lorenzo F., Jessica Keto, and Muller Fabbri. 2017. Exosomal microRNAs in breast cancer towards diagnostic and 

therapeutic applications. Cancers 9(7): 71. 


Valkenburg, Kenneth C., Angelo M. De Marzo, and Bart O. Williams. 2017. Deletion of tumor suppressors adenomatous polyposis 

coli and Smad4 in murine luminal epithelial cells causes invasive prostate cancer and loss of androgen receptor expression. 

Oncotarget 8(46): 80265–80277. 

Waldhart, Althea N., Holly Dykstra, Anderson S. Peck, Elissa A. Boguslawski, Zachary B. Madaj, Jennifer Wen, Kelsey Veldkamp, 

Matthew Hollowell, Bin Zheng, Lewis C. Cantley, Timothy E. McGraw, and Ning Wu. 2017. Phosphorylation of TXNIP by AKT 

mediates acute influx of glucose in response to insulin. Cell Reports 19(10): 2005–2013. 

Winkler, Paige A., Yihe Huang, Weinan Sun, Juan Du, and Wei Lü. 2017. Electron cryo-microscopy structure of a human TRPM4 

channel. Nature 552(7684): 200–204. 

Yan, Yan, Ting-Hai Xu, Kaleeckal G. Marikumar, Laurence J. Miller, Karsten Melcher, and H. Eric Xu. 2017. Dimerization of the 

transmembrane domain of amyloid precursor protein is determined by residues around the gamma-secretase cleavage sites. 

Journal of Biological Chemistry 292(38): 15826–15837. 

Yang, Tao, and Bart O. Williams. 2017. Low-density lipoprotein receptor-related proteins in skeletal development and disease. 

Physiological Reviews 97(3): 1211–128. 

Yin, Yanting, Parker W. De Waal, Yuanzheng He, Li-Hua Zhao, Dehua Yang, Xiaoqing Cai, Yi Jiang, Karsten Melcher, Ming-Wei 

Wang, and H. Eric Xu. 2017. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of 

class B G protein–coupled receptors. Journal of Biological Chemistry 292(24): 9865–9881. 

Zhang, Feng, Jiyuan Ke, Li Zhang, Rongzhi Chen, Koichi Sugimoto, Gregg A. Howe, H. Eric Xu, Mingguo Zhou, Sheng Yang 

He, and Karsten Melcher. 2017. Structural insights into alternative splicing-mediated desensitization of jasmonate signaling. 

Proceedings of the National Academy of Sciences U.S.A. 114(7): 1720–1725. 

Zhou, X. Edward, Yuanzheng He, Parker W. de Waal, Xiang Gao, Yanyong Kang, Ned Van Eps, Yanting Yin, Kuntal Pal, Devrishi 

Goswami, Thomas A. White, Anton Barty, Naomi R. Latorraca, Henry N. Chapman, Wayne L. Hubbell, Ron O. Dror, Raymond 

C. Stevens, Vadim Cherezov, Vsevolod V. Gurevich, Patrick R. Griffin, Oliver P. Ernst, Karsten Melcher, and H. Eric Xu. 2017. 

Identification of phosphorylation codes for arrestin recruitment by G protein–coupled receptors. Cell 170(3): 457–469.e13. 


Center for Epigenetics 

Peter A. Jones, Ph.D., D.Sc. 

Director 

The Center’s researchers study epigenetics and 

epigenomics in health and disease, with the 

ultimate goal of developing novel therapies to 

treat cancer and neurodegenerative diseases. 

The Center collaborates extensively with other 

VARI research groups and with external partners 

to maximize its efforts to develop therapies that 

target epigenetic mechanisms. 


Methyl (red) and acetyl (light blue) 

groups as epigenetic marks on 

nucleosomes and DNA. Image by Nicole 

Ethen, formerly of the Williams lab.


STEPHEN B. BAYLIN, M.D. 

Dr. Baylin joined VARI as a Professor and Director's Scholar in the 

Center for Epigenetics in January 2015. He is co-leader of the VARI-SU2C 

Epigenetics Dream Team, and he devotes a portion of his time to VARI. His 

primary appointment is at Johns Hopkins University as the Virginia and 

D.K. Ludwig Professor of Oncology and Medicine and as co-head of Cancer 

Biology at the Sidney Kimmel Comprehensive Cancer Center. 


The Van Andel Research Institute–Stand Up To Cancer (VARI-SU2C) Epigenetics 

Dream Team is a multi-institutional effort to develop new epigenetic therapies 

against cancer and to move promising therapies to clinical trials. As co-leader, Dr. 

Baylin oversees the team’s research, which leverages the combined expertise of its 

members. 

Epigenetics is the study of how the packaging and modification of DNA influences 

the genes that are active or kept silent in a particular cell, and it holds untold 

potential for treating cancer and other diseases. Through a detailed understanding of 

how normal epigenetic processes work, scientists can identify erroneous epigenetic 

modifications that may contribute to the development and progression of cancer. 

Epigenetic therapies, which work by correcting these errors, have the potential 

to directly treat cancer and to sensitize patients to traditional treatments such as 

chemotherapy and promising new immunotherapy approaches. 

The VARI-SU2C Epigenetics Dream Team is headquartered at VARI in Grand Rapids, 

Michigan. It includes members from Fox Chase Cancer Center, Garvan Institute 

of Medical Research, Indiana University, Johns Hopkins University, Memorial 

Sloan Kettering Cancer Center, Rigshospitalet/University of Copenhagen, Temple 

University, University of Maryland, and University of Southern California. The 

American Association for Cancer Research, as SU2C’s scientific partner, reviews 

projects and provides objective scientific oversight. 


PETER A. JONES, Ph.D., D.Sc. 

Dr. Jones received his Ph.D. from the University of London. He joined the 

University of Southern California in 1977 and served as Director of the USC 

Norris Comprehensive Cancer Center between 1993 and 2011. Dr. Jones 

joined VARI in 2014 as its Chief Scientific Officer and Director of the Center 

for Epigenetics. 


Our laboratory uses a holistic approach to determine how DNA methylation, 

nucleosome positioning, and histone modifications influence each other to bring 

about epigenetic changes that contribute to cancer. Some current and recent projects 

are summarized here. 

STAFF 

Brittany Carpenter, Ph.D. 

Ashley DeWitt, M.S. 

Minmin Liu, Ph.D. 

Amy Nelson 

Hitoshi Otani, Ph.D. 

Stacey Thomas, Ph.D. 

Rochelle Tiedemann, Ph.D. 

Tinghai (Peter) Xu, Ph.D. 

Wanding Zhou, Ph.D. 

Both DNA and histone modifications play important roles in suppressing 

endogenous retrovirus (ERV) expression in mammalian cells. ERVs, which have 

populated the human genome for more than 100 million years, are CpG-rich at the 

time of infection, but they have lost CpG content over such long time periods. We 

are currently examining ERVs of different ages to determine their mechanism of 

silencing and their ability to induce the expression of viral defense genes. The data 

suggest that there is an epigenetic switch in the silencing mechanism, such that 

older ERVs are predominately silenced by histone modification rather than DNA 

methylation. 

Following up our finding that DNA methylation inhibitors induce a state of “viral 

mimicry” in cancer cells, we have found that treatment of cells with a low dose of 

5-azanucleoside plus vitamin C enhanced immune signals, including the increased 

expression of ERVs. Because many patients with hematological neoplasia are 

vitamin C–deficient, correction of this deficiency may improve patient response to 

epigenetic therapy. This work has led to an ongoing VARI-SU2C pilot clinical trial in 

adult patients who have MDS or AML, to assess whether vitamin C supplements can 

increase patient response to DNA methylation inhibitors. 

Another focus of the lab is the noncoding RNA nc886 (vtRNA2-1), which is variably 

imprinted by methylation from the mother during development and is strongly 

associated with the risk of both obesity and cancer. We will define the mechanism of 

this variable imprinting, examine the role of nc886 in normal cell physiology, and 

determine how chromatin structure and DNA methylation silence nc886. 

Taking advantage of VARI’s latest cryo-EM instrument, the Titan Krios G2, we have 

begun work to solve the structures of the DNA methyltransferases DNMT3A and 

DNMT3B bound to nucleosomes. This information will increase our understanding of 

how DNA methylation patterns are established and maintained by these enzymes. 



STEFAN JOVINGE, M.D., Ph.D. 

Dr. Jovinge received his M.D. (1991) and his Ph.D. (1997) at Karolinska 

Institute in Stockholm. Since December 2013 he has been a Professor at 

VARI and the Medical Director of Research at the Frederik Meijer Heart and 

Vascular Institute. He also directs the DeVos Cardiovascular Research 

Program, is a Professor at the MSU College of Human Medicine, and is a 

Consulting Professor at Stanford University. 


The DeVos Cardiovascular Research Program is a joint effort between VARI and 

Spectrum Health. The basic science lab is the Jovinge laboratory at VARI, and a 

corresponding clinical research unit resides within the Fred Meijer Heart and 

Vascular Institute. 

STAFF 

Lucas Chan, Ph.D. 

Shelby Compton 

Paula Davidson, M.S. 

Lisa DeCamp, M.A., MB(ASCP), RLAT 

Ellen Ellis 

Emily Eugster, M.S. 

Joseph Faski, B.S. 

Jens Forsberg, Ph.D. 

Eric Kort, M.D. 

Olivia Licari 

Hsiao-Yun Yeh (Christy) Milliron, Ph.D. 

Matthew Weiland, M.S. 

To regenerate myocardium after disease or damage is one of the major challenges 

in medicine. We have shown that endogenous generation of heart muscle cells 

in humans is continuous throughout life. However, it declines rapidly with age 

and is far too insufficient to compensate for the large loss of muscle cells seen in 

most diseased hearts. Our preliminary data support the concept that preexisting 

cardiomyocytes are the source of this endogenous generation. We have now been 

able to isolate dividing cardiomyocytes based on their gene expression pattern. 

Thus, we are working our way toward control of the endogenous generation of 

cardiomyocytes and thereby toward the possibility of developing strategies to 

enable the heart to heal itself. 

“Rare diseases” affect fewer than 200,00 individuals in the USA; while each patient 

group is small, together rare diseases encompass some 30 million individuals. The 

generation of drugs for such small populations is very costly, so those who have 

such diseases are often left without specific treatment. With the use of the NIH 

database LINCS, which screens all FDA-approved drugs for off-target effects, we 

have identified a drug that specifically targets the deficiency in patients who have a 

rare mutation that causes a severe heart muscle disease. By reprogramming blood 

cells and deriving heart muscle cells from these patients, we have been able to verify 

the database predictions for the drug, thereby making possible the availability of 

new drugs for patients with this rare disease at a reasonable cost. 

Using a sophisticated technology, we have been able to reprogram and derive cardiac 

pacemaker cells. This year, we were able to use pacemaker cells to create a biological 

pacemaker in a culture dish. In another study, we have created a large database that 

allows us to optimize treatment for patients who have severe heart failure and are 

on mechanical support. We can also create advanced algorithms for predicting the 

outcome of support selection and for preventing complications. 


PETER W. LAIRD, Ph.D. 

Dr. Laird earned his Ph.D. in 1988 from the University of Amsterdam 

with Piet Borst. He was a faculty member at the University of Southern 

California from 1996 to 2014, where he was Skirball-Kenis Professor of 

Cancer Research and directed the USC Epigenome Center. He joined VARI 

as a Professor in September 2014. 

STAFF 

Kelly Foy, B.S. 

Walid Habib, Ph.D. 

Toshinori Hinoue, Ph.D. 

Manpreet Kalkat, Ph.D. 

Liang Kang, A.S. 

KwangHo Lee, Ph.D. 

Amy Nelson 


STUDENTS 

Zack Jansen 


Our goal is to develop a detailed understanding of the molecular basis of human 

disease, with a particular emphasis on the role of epigenetics in cancer. Cancer is 

often considered to have a primarily genetic basis, with contributions from germline 

variations in risk and somatically acquired mutations, rearrangements, and copy 

number alterations. However, it is clear that nongenetic mechanisms can exert a 

powerful influence on cellular phenotype, as evidenced by the marked diversity of 

cell types within our bodies, which virtually all contain an identical genetic code. 

This differential gene expression is controlled by tissue-specific transcription 

factors and variations in chromatin packaging and modification, which can provide 

stable phenotypic states governed by epigenetic, not genetic, mechanisms. It seems 

likely that an intrinsically opportunistic disease such as cancer would take advantage 

of such a potent mediator of cellular phenotype. Our laboratory is dedicated to 

understanding how epigenetic mechanisms contribute to the origins of cancer and 

how to translate this knowledge into more-effective cancer prevention, detection, 

treatment, and monitoring. 

We use a multidisciplinary approach in our research, relying on mechanistic studies 

in model organisms and cell cultures, clinical and translational collaborations, 

genome-scale and bioinformatic analyses, and epidemiological studies to advance 

our understanding of cancer epigenetics. In recent years, we participated in the 

generation and analysis of high-dimensional epigenetic data sets, including 

the production of all epigenomic data for The Cancer Genome Atlas (TCGA) and 

the application of next-generation sequencing technology to whole-genome 

DNA methylation analysis at single-base-pair resolution. We are leveraging this 

epigenomic data for translational applications and hypothesis testing in animal 

models. A major focus of our laboratory is to develop mouse models for investigating 

epigenetic mechanisms and drivers of cancer and to develop novel strategies for 

single-cell epigenomic analysis. 

Nicole Vander Schaaf, B.S. 



HUILIN LI, Ph.D. 

Dr. Li earned his Ph.D. in electron crystallography from the University of 

Science and Technology Beijing, where he trained with the late K. H. Kuo. 

He joined VARI in 2016 from Stony Brook University, New York. 


The work of our lab focuses on the structural basis of DNA replication, the bacterial 

proteasome system, and the regulation and modification of the Notch receptor. 

STAFF 

Lin Bai, Ph.D. 

Xiang Feng, Ph.D. 

Hao-Chi Hsu, Ph.D. 

Amanda Kovach, B.S. 

Hua Li, Ph.D. 


Yanting Yin, Ph.D. 

Hongjun Yu, Ph.D. 

Eukaryotic DNA replication 

Replication initiation is tightly regulated, because failure to ensure once-only 

initiation per cell cycle can result in uncontrolled proliferation and genomic 

instability, which are hallmarks of tumorigenesis. We use structural and biochemical 

approaches to uncover the molecular mechanisms underlying eukaryotic 

chromosomal replication. Work in our lab over the past year has revealed how 

ORC, with the help of Cdc6, loads the Mcm2-7 hexamer and how the Mcm2-7 

double-hexamer binds the origin DNA. In the S phase of the cell cycle, the active 

Cdc45–Mcm2-7–GINS helicase (CMG) works with the leading strand polymerase 

epsilon, the lagging strand polymerase delta, and the primase-polymerase alpha to 

synthesize new DNA. We also determined the structure of the 11-protein yeast CMG 

helicase and have shown how the helicase interacts with the replication fork DNA. 

Proteostasis in Mycobacterium tuberculosis 

Tuberculosis kills some 1.5 million people globally every year. Mycobacterium 

tuberculosis can be killed by nitric oxide (NO) of the host immune system. The 

Mtb proteasome is a key to the organism’s resistance to such attack and thus is a 

promising target for the development of anti-TB chemotherapeutics. In the past 

year, we have solved the structure of the ATPase-dependent proteasomal activator 

Mpa and the ATP-independent proteasomal activator PafE. We also uncovered the 

structural basis for the species-selective binding of six N,C-capped dipeptides to 

the Mtb proteasome. Our work illuminates the bacterial proteasome system and 

facilitates anti-TB chemotherapeutic development efforts. 

STUDENTS 

Minge Du, M.S. 

Ruda Santos, M.S. 

Zuanning Yuan, M.S. 


GERD PFEIFER, Ph.D. 

Dr. Pfeifer earned his M.S. in pharmacology in 1981 and his Ph.D. in 

biochemistry in 1984 from Goethe University in Frankfurt, Germany. He 

most recently held the Lester M. and Irene C. Finkelstein Chair in Biology 

at the City of Hope in Duarte, California, before joining VARI in 2014 as 

a Professor. 

RESEARCH OVERVIEW 

The laboratory studies epigenetic mechanisms of human diseases, with a focus on 

DNA methylation and the role of 5-methylcytosine oxidation by the TET protein 

family. 

STAFF 

Zhijun Huang, Ph.D. 

Seung-Gi Jin, Ph.D. 

Jennifer Johnson, M.S. 

Amy Nelson 

Zhi-Qiang (Ken) Wang, Ph.D. 

DNA methylation in cancer 

This work centers on the hypothesis that CpG islands are protected from 

methylation in normal cells by a set of specific proteins, such as 5-methylcytosine 

oxidases, CXXC proteins, and the polycomb complex. The protection breaks 

down during early stages of malignancy. We investigate mechanisms of DNA 

hypermethylation using DNA-methylation mapping and chromatin mapping in both 

normal and malignant cells, as well as bioinformatic approaches and functional 

studies employing gene inactivation in tissue culture. 

TET3 and related proteins in basic biology and human disease 

The removal of methyl groups from DNA has been recognized as an important 

pathway in cancer and possibly in other diseases. Our lab studies mechanisms 

of 5-methylcytosine oxidation. We have identified three isoforms of the TET3 

5-methylcytosine oxidase and characterized them using biochemical, functional, 

and genetic approaches. We observed that one isoform of TET3 specifically binds 

to 5-carboxylcytosine, thus establishing an anchoring mechanism of TET3 to 

its reaction product, which may aid in localized 5-methylcytosine oxidation and 

removal. We also study several TET3-associated proteins, trying to understand 

their biological roles. TET3 has a rather limited genomic distribution and is targeted 

to the transcription start sites of defined sets of genes, many of which function 

within the lysosome and autophagy pathways. We are exploring the mechanistic 

consequences of 5-methylcytosine oxidation in these genes, with the long-term 

goal of determining whether neurodegeneration has an epigenetic origin. In another 

project, we are exploring the function of a TET3-binding protein and its effect on 

TET-mediated processes in embryonic stem cells and in myoblasts. This work has 

implications for understanding the mechanisms underlying muscular dystrophy. 



SCOTT ROTHBART, Ph.D. 

Dr. Rothbart earned a Ph.D. in pharmacology and toxicology from Virginia 

Commonwealth University in 2010. He joined VARI in April 2015 as an 

Assistant Professor. 


The long-term goal of my research program is to define molecular mechanisms 

regulating chromatin modification signaling. Through a multidisciplinary and 

collaborative research program, we hope to translate basic knowledge of epigenetic 

mechanisms into therapeutic benefits. 

STAFF 

Evan Cornett, Ph.D. 

Bradley Dickson, Ph.D. 

Alison Lanctot, Ph.D. 

Amy Nelson 

Kevin Shaw, B.S. 

Rochelle Tiedemann, Ph.D. 

STUDENTS 

We are keen on understanding the complex relationship between DNA methylation 

and histone post-translational modifications (PTMs); these are two key epigenetic 

regulators of genome accessibility, interaction, and function. Within this broad 

framework, we ask 1) how are the writers and erasers of chromatin modifications 

regulated? 2) how do nuclear proteins and their complexes interface with (i.e., read) 

epigenetic marks to perform their chromatin regulatory functions? and 3) how does 

deregulation of chromatin signaling contribute to human diseases like cancer? 

We fabricate histone peptide microarrays in my lab as an integral part of our effort 

to characterize the complex interactions of proteins with the DNA and histone 

components of chromatin. We use this platform extensively to characterize the 

reader, writer, and eraser activities of chromatin regulators and also the behavior of 

antibodies that recognize histones and their PTMs. 

We are also developing new functional proteomics techniques to study the writers, 

erasers, and readers of lysine methylation signaling. Our studies are providing 

crucial systems-level information for the construction of lysine methylation 

signaling networks, are aiding drug discovery and development efforts, and are 

improving our understanding of lysine methylation function in human health and 

disease. 

Christine Ausherman 

Robert Vaughan, B.S. 

Philip Versluis 


HUI SHEN, Ph.D. 

Dr. Shen earned her Ph.D. at the University of Southern California in 

genetic, molecular, and cellular biology. She joined VARI in September 

2014 as an Assistant Professor. 

STAFF 

Huihui Fan, Ph.D. 

Hongbo Liu, Ph.D. 

Amy Nelson 



The laboratory focuses on the epigenome and its interaction with the genome in 

various diseases, with a specific emphasis on cancers of women and cross-cancer 

comparisons. We use bioinformatics as a tool to understand the etiology, cell of 

origin, and epigenetic mechanisms of disease and to devise better approaches 

for cancer prevention, detection, therapy, and monitoring. We have extensive 

experience with genome-scale DNA methylation profiles in primary human samples, 

and we have made major contributions to epigenetic analysis within The Cancer 

Genome Atlas (TCGA). 

DNA methylation is ideally suited for deconstructing heterogeneity among cell types 

within a tissue sample. In cancer research, this approach can be used for cancer 

cell clonal evolution studies or for quantifying normal cell infiltration and stromal 

composition. The latter can provide insights into the tumor microenvironment, and 

in noncancer studies it can be a useful tool for accurately estimating cell populations 

and providing insights into lineage structures and population shifts in disease. In 

addition, we are interested in translational applications of epigenomic technology. 

To this end, we bring markers emerging from our bioinformatics analysis into 

clinical assay development, marker panel assembly, and optimization, with the 

ultimate goal of clinical testing and validation. 



PIROSKA E. SZABÓ, Ph.D. 

Dr. Szabó earned an M.Sc. in biology and a Ph.D. in molecular biology from 

József Attila University, Szeged, Hungary. She joined VARI in 2014 as an 

Associate Professor. 


Our laboratory studies the molecular mechanisms responsible for resetting the 

mammalian epigenome between generations, globally and specifically in the context 

of genomic imprinting. We focus on how DNA methylation patterns are established 

in germ cells and how some of those are protected in the zygote and in the embryo. 

STAFF 

Brianna Bixler, B.S. 

Ji Liao, Ph.D. 

Amy Nelson 

Tie-Bo Zeng, Ph.D. 

STUDENTS 

Brianna Busscher 

Yingying Meng, M.S. 

The role of broad transcription and dynamic chromatin changes in the germline 

Correctly setting up male or female gamete-specific methylation patterns is vitally 

important for fertility, development, and health. Our genome-wide mapping results 

have revealed that DNA methylation in fetal male germ cells (prospermatogonia) 

occurs by default along a profile of broad, low-level transcription. We have also 

found that dynamically increasing or diminishing H3K4 methylation at specific 

sequences is predictive of escaping or attaining DNA methylation, respectively, in 

the male germline. We hypothesize that transcription run-through is required for 

establishing default, broad DNA methylation in the prospermatogonia genome, 

including paternal imprinted differentially methylated regions (DMRs). Dynamic 

changes in H3K4me by H3K4 demethylases (KDMs) and H3K4 methyltransferases 

(HMTs), on the other hand, provide a pattern for de novo DNA methylation. We are 

addressing these questions using experimental approaches of mouse genetics and 

epigenomics. 

Maternal effects of histone methyltransferases 

Crucial events in the early embryo, such as reaching totipotency and embryonic 

genome activation, depend on accurate levels of epigenetic modifiers deposited in 

the egg. We are only beginning to understand the underlying epigenetic mechanisms 

in these events. We and others have shown that genome-wide DNA demethylation 

in the zygote involves sequential TET-mediated oxidation of 5mC to 5hmC, 5fC, and 

5caC in the paternal pronucleus. Specific loci and the entire maternal pronucleus, 

however, are protected from TET-initiated DNA demethylation; this protection 

involves histone H3K9 methylation. Using mouse genetics and epigenomics, we 

will genetically identify the mechanistic connections between maternally deposited 

HMTs, DNA methylation, and the developmental potential of the embryo. 


TIMOTHY J. TRICHE, JR., Ph.D. 

Dr. Triche earned his Ph.D. from the University of Southern California in 

2013. He joined VARI in the autumn of 2017 as an Assistant Professor in the 

Center for Epigenetics. 


Our laboratory develops statistical and mathematical methods to dissect 

pediatric and adult diseases, with a focus on cancers of the blood in children. We 

study interactions between genetic factors and environmental factors (deficiencies 

and exposures), particularly where epigenetic mediation plays a major role, such 

as in immune response and evasion. 

STAFF 

Amy Nelson 



STEVEN J. TRIEZENBERG, Ph.D. 

Dr. Triezenberg earned his Ph.D. at the University of Michigan. He was a 

faculty member at Michigan State University for more than 18 years before 

joining VARI in 2006 as the founding Dean of Van Andel Institute Graduate 

School and as a VARI Professor. 


Our research explores the mechanisms that control how genes are expressed inside 

cells, with a special interest in the processes that activate transcription of genetic 

information from DNA into RNA. We study those mechanisms in the context of 

infection by herpes simplex virus type 1 (HSV-1), the cause of cold sores. 

STAFF 

Glen Alberts, B.S. 

Susanne Miller-Schachinger, B.B.A. 

. 

STUDENT 

Nikki Thellman, D.V.M. (Ph.D., May 2017) 

Some of our work looks at early stages of lytic or productive infection by HSV-1, 

which results in the obvious (and painful) cold-sore symptoms near the mouth. We 

have explored how a particular viral protein, VP16, activates the first viral genes that 

are expressed during lytic infection. We are now looking at proteins of the host cell 

that affect the early stages of infection, some of which control how the virus gets 

into a cell and some that control how the VP16 protein performs its functions. This 

approach may yield new ideas for antiviral drugs that can block HSV infections. 

After the initial infection resolves, HSV-1 finds its way into nerve cells, where the 

virus can remain in a latent mode for the entire life of the host. Occasionally, some 

stressful event will cause the latent virus to reactivate, producing new viruses in 

the nerve cell and sending them back to the skin to cause a recurrence of the cold 

sore. We are investigating the role that VP16 might play during this reactivation. 

We are especially interested in the epigenetic regulators that might be involved in 

unpacking the chromatin that silences the latent viral DNA. Our present hypothesis 

is that epigenetic coactivators recruited by VP16 are required to open up chromatin 

as an early step in reactivating the viral genes from latency. We are currently testing 

this hypothesis in quiescent infections of cultured human nerve cells. 



Azad, Nilofer S., Anthony el-Khoueiry, Jun Yin, Ann L. Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J. 

Weisenberger, Thomas Brown, Prakriti Medvari, Peter A. Jones, Hariharan Easwaran, Ihab Kamel, Nathan Bahary, George Kim, 

Joel Picus, Henry C. Pitot, Charles Erilichman, Ross Donehower, Hui Shen, Peter W. Laird, Richard Piekarz, Stephen Baylin, and 

Nita Ahuja. 2017. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and 

entinostat: a phase 2 consortium/Stand Up 2 Cancer study. Oncotarget 8(21): 35326–35338. 

Cancer Genome Atlas Research Network, The. 2017. Integrated genomic characterization of oesophageal carcinoma. Nature 

541(7636): 169–175. 

Cherniack, Andrew D., Hui Shen, Vonn Walter, Chip Stewart, Bradley A. Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert 

A. Soslow, Russell R. Broaddus, Rosemary E. Zuna, Gordon Robertson, Peter W. Laird, Raju Kucherlapati, Gordon B. Mills, 

The Cancer Genome Atlas Research Network, John N. Weinstein, Jiashan Zhang, Rehan Akbani, and Douglas A. Levine. 2017. 

Integrated molecular characterization of uterine carcinosarcoma. Cancer Cell 31(3): 411–423. 

Connolly, Roisin M., Huili Li, Rachel C. Jankowitz, Zhe Zhang, Michelle A. Rudek, Stacie C. Jeeter, Shannon A. Slater, Penny 

Powers, Antonio C. Wolff, John H. Fetting, Adam Burufsky, Richard Piekarz, Nita Ahuja, Peter W. Laird, Hui Shen, Daniel J. 

Weisenberger, Leslie Cope, James G. Herman, George Somlo, Garcia Agustin A., Peter A. Jones, Stephen B. Baylin, Nancy E. 

Davidson, Cynthia A. Zahnow, and Vered Stearns. 2017. Combination epigenetic therapy in advanced breast cancer with 

5-azacitidine and entinostat: a Phase II National Cancer Institute/Stand Up to Cancer study. Clinical Cancer Research 23(11): 

2691–2701. 

Cornett, Evan M., Bradley M. Dickson, and Scott B. Rothbart. 2017. Analysis of histone antibody specificity with peptide 

microarrays. Journal of Visualized Experiments 126: e55912. 

Georgescu, Roxana, Zuanning Yuan, Lin Bai, Ruda de Luna Almeida Santos, Jingchuan Sun, Dan Zhang, Olga Yurieva, Huilin 

Li, and Michael E. O’Donnell. 2017. Structure of eukaryotic CMG helicase at a replication fork and implications to replisome 

architecture and origin initiation. Proceedings of the National Academy of Sciences U.S.A. 114(5): D697–E706. 

Hanley, M.P., M.A. Hahn, A.X. Li, X. Wu, J. Lin, A.H. Choi, Z. Ouyang, Y. Fong, G.P. Pfeifer, T.J. Devers, and D.W. Rosenberg. 2017. 

Genome-wide DNA methylation profiling reveals cancer-associated changes within early colonic neoplasia. Oncogene 36(35): 

5035–5044. 

Helbo, Alexandra Søgaard, Fides D. Lay, Peter A. Jones, Gangning Liang, and Kirsten Grønbaek. 2017. Nucleosome positioning 

and NDR structure at RNA polymerase III promoters. Scientific Reports 7: 41947 

Lakshminarasimhan, Ranjani, Claudia Andreu-Vieyra, Kate Lawrenson, Christopher E. Duymich, Simon A. Gayther, Gangning 

Liang, and Peter A. Jones. 2017. Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with 

epigenetic reprogramming in non-tumorigenic endometriotic cells. Cancer Letters 401: 11–19. 

Lee, Kwang-Ho, Shirley Oghamian, Jin-A Park, Liang Kang, and Peter W. Laird. 2017. The REMOTE-control system: a system 

for reversible and tunable control of endogenous gene expression in mice. Nucleic Acids Research 45(21): 12256–12269. 

Ma, Honglei, Jingbo Duan, Jiyuan Ke, Yuanzheng He, Xin Gu, Ting-Hai Xu, Hong Yu, Yonghong Wang, Joseph S. Brunzelle, Yi 

Jiang, Scott B. Rothbart, H. Eric Xu, Jiayang Li, and Karsten Melcher. 2017. A D53 repression motif induces oligomerization of 

TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex. Science Advances 3(6): e1601217. 

Noguchi, Yasunori, Auanning Yuan, Lin Bai, Sarah Schneider, Gongpu Zhao, Bruce Stillman, Christian Speck, and Huilin Li. 2017. 

Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proceedings of the 

National Academy of Sciences U.S.A. 114(45): E9529–E9538. 



RECENT CENTER PUBLICATIONS (cont.) 

Olsson, P., E. Theander, U. Bergström, S. Jovinge, L.T.H. Jacobsson, and C. Turesson. 2017. Multiplex cytokine analyses in 

patients with rheumatoid arthritis require use of agents blicking heterophilic antibody activity. Scandanavian Journal of 

Rheumatology 46(1): 1–10. 

Polak, Paz, Jaegil Kim, Lior Z. Braunstein, Rosa Karlilc, Nicholas J. Haradhavala, Grace Tiao, Daniel Rosebrock, Dimitri Livitz, 

Kirsten Kübler, Kent W. Mouw, Atanas Kamburov, Yosef E. Maruvka, Ignaty Leshchiner, Eric S. Lander, Todd R. Golub, Aviad 

Zick, Alexandre Orthwein, Michael S. Lawrence, Rajbir N. Batra, Carlos Caldas, Daniel A. Haber, Peter W. Laird, Hui Shen, Leif 

W. Ellisen, Alan D. D’Andrea, Stephen J. Chanock, William D. Foulkes, and Gad Getz. 2017. A mutational signature reveals 

alterations underlying deficient homologous recombination repair in breast cancer. Nature Genetics 49(10): 1476–1486. 

Robertson, A. Gordon, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D. Cherniak, Toshinori 

Hinoue, Peter W. Laird, Katherine A. Hoadley, Rehan Akbani, et al. 2017. Comprehensive molecular characterization of muscleinvasive 

bladder cancer. Cell 171(3): 540–556.e25. 

Shanle, Erin K., Stephen A. Shinsky, Joseph B. Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B. Rothbart, Mark 

T. Bedford, and Brian D. Strahl. 2017. Histone peptide microarray screen of chromo and Tudor domains defines new histone 

lysine methylation interactions. Epigenetics and Chromatin 10: 12. 

Thellman, Nikki M., Carolyn Botting, Zachary Madaj, and Steven J. Triezenberg. 2017. An immortalized human dorsal root 

ganglia cell line provides a novel context to study herpes simplex virus Type-1 latency and reactivation. Journal of Virology 

91(12): 00080-17. 

Thellman, Nikki M., and Steven J. Triezenberg. 2017. Herpes simplex virus establishment, maintenance, and reactivation: 

in vitro modeling of latency. Pathogens 6(3): 28. 

Veland, Nicolas, Swanand Hardikar, Yi Zhong, Sitaram Sayatri, Jiameng Dan, Brian D. Strahl, Scott B. Rothbart, Mark T. Bedford, 

and Taiping Chen. 2017. The arginine methyltransferase PRMT6 regulates DNA methylation and contributes to global DNA 

hypomethylation in cancer. Cell Reports 21(12): 3390–3397. 

Weng, Xi-Lan, Ran An, Jessica Cassin, Jessica Joseph, Ruifa Mi, Chen Wang, Chun Zhong, Seung-Gi Jin, Gerd P. Pfeifer, Alfonso 

Bellacosa, Xinzhong Dong, Ahmet Hoke, Zhigang He, Hongjun Song, and Guo-li Ming. 2017. An intrinsic epigenetic barrier for 

functional axon regeneration. Neuron 94(2): 337–346. 

Wu, Yujie, Kuan Hu, Defeng Li, Lin Bai, Shaoqing Yang, Jordan B. Jastrab, Shuhao Xiao, Yonglin Hu, Susan Zhang, K. Heran 

Darwin, Tao Wang, and Huilin Li. 2017. Mycobacterium tuberculosis proteasomal ATPase Mpa has a β-grasp domain that hinders 

docking with the proteasome core protease. Molecular Microbiology 105(2): 227–241. 

Yuan, Zuanning, Alberto Riera, Lin Bai, Jingchuan Sun, Saikat Nandi, Christos Spanos, Zhuo Angel Chen, Marta Barbon, Juri 

Rappsilber, Bruce Stillman, Christian Speck, and Huilin Li. 2017. Structural basis of Mcm2–7 replicative helicase loading by 

ORC–Cdc6 and Cdt1. Nature Structural & Molecular Biology 24(3): 316–324. 

Zhou, Wanding, Peter W. Laird, and Hui Shen. 2017. Comprehensive characterization, annotation and innovative use of 

Infinium DNA methylation BeadChip probes. Nucleic Acids Research 45(4): e22. 


A side view of the cryo-EM density map of the S. cerevisiae Mcm2-7 double hexamer, with 

individual subunits labeled. The two hexamers are stacked at a tilt angle of 14°. 

Image from Huilin Li’s laboratory. 


Center for Neurodegenerative Science 

Patrik Brundin, M.D., Ph.D. 

Director 

The Center's laboratories focus on developing 

novel treatments that slow or halt the progression 

of neurodegenerative disease, in particular 

Parkinson’s disease. The work involves three main 

goals: disease modification, biomarker discovery, 

and brain repair. 


Neurons from the brain of a mouse 

model of Parkinson’s disease. The 

neurons are stained green, cell nuclei are 

stained blue with DAPI, and pathological 

inclusions of α-synuclein are stained red. 

Image by Nolwen Rey of the 

Patrik Brundin lab.


LENA BRUNDIN, M.D., Ph.D. 

Dr. Brundin earned her Ph.D. in neurobiology and her M.D. from Lund 

University, Sweden. She joined VARI in 2012 and is an Associate Professor. 


We hypothesize that inflammation in the brain causes psychiatric symptoms 

such as depression and thoughts of suicide, and we study how inflammation can 

damage nerve cells and be involved in neurological conditions such as Parkinson’s 

disease. We are conducting clinical studies on patients in the Grand Rapids area 

and translational experiments in the laboratory at VARI, trying to understand the 

mechanisms by which inflammation affects the brain. 

STAFF 

Elena Bryleva, Ph.D. 

Nils Eastburg, B.S. 

Emily Glidden, B.S. 

Stan Krzyzanowski, B.A. 

Keerthi Rajamani, Ph.D. 

Infections may play a role in triggering inflammation and subsequent symptoms in 

patients. In collaboration with Pine Rest Christian Mental Health, we are assessing 

the role of herpes simplex virus infection in triggering psychiatric symptoms. Our 

hypothesis is that patients with depression are more vulnerable to developing mood 

symptoms upon reactivation of HSV infection and that the infection could trigger 

depressive episodes. 

We have found that infection with the parasite Toxoplasma gondii is associated with 

a sevenfold risk of attempted suicide. Some 10-20% of all Americans are infected 

with this parasite, which may cause subtle behavioral changes, perhaps due to 

low-grade chronic brain inflammation. Toxoplasma infection may be treatable using 

current medications, but clinical trials are needed to prove that such treatment has a 

beneficial effect on depressive and suicidal behavior. 

STUDENT 

Sarah Keaton, M.S. 

We are conducting a study of perinatal depression together with Pine Rest Christian 

Mental Health, Spectrum Health, and Michigan State University. This NIH-funded 

effort, led by Dr. Brundin, investigates the role of placental inflammation in the 

development of perinatal depression. The goals of the study are to understand the 

cause of depression during pregnancy and to find biomarkers to identify women 

who are at risk for such depression. We have successfully enrolled 199 women and 

evaluated them in pregnancy and post partum over the past three years, and we are 

now analyzing the data. 

We have identified an enzyme, aminocarboxymuconate semialdehyde decarboxylase 

(ACMSD), that may regulate the vulnerability to developing psychiatric and 

neurological symptoms upon infection or inflammation. A person having low activity 

of ACMSD might have difficulties in controlling inflammation. The by-products 

of inflammation may cause nerve cell damage and neurological and psychiatric 

symptoms. We are studying whether increased amounts of ACMSD can be protective 

and prevent symptoms of Parkinson’s disease and depression. 


PATRIK BRUNDIN, M.D., Ph.D. 

Dr. Brundin earned his M.D. and Ph.D. at Lund University, Sweden. He was 

a professor of neuroscience at Lund before becoming a Professor and 

Associate Research Director of VARI in 2012. 


Our research mission is to understand why Parkinson’s disease (PD) develops. We 

use cellular and animal PD models to discover new treatments that we hope can slow 

disease progression. 

STAFF 

Kim Cousineau, M.P.A. 

Sonia George, Ph.D. 

Lindsay Meyerdirk, M.S. 

Wouter Peelaerts, Ph.D. 

Emmanuel Quansah, Ph.D. 

Keerthi Rajamani, Ph.D. 

Nolwen Rey, Ph.D. 

Emily Schulz, B.S. 

Jennifer Steiner, Ph.D. 

Misfolded variants of the protein α-synuclein (α-syn) are a main constituent 

of intraneuronal Lewy bodies, the protein aggregates that are the major 

neuropathological hallmark of PD. The mechanisms underlying α-syn pathology are 

poorly understood. We were one of the first groups to propose that abnormal α-syn 

might propagate between neurons and drive the progression of symptoms. 

Our interests include understanding how α-syn aggregation is triggered, how the 

aggregates spread, and how they cause neurological deficits. We have created a 

mouse model of the human disease based on injections of misfolded α-syn into 

the olfactory bulb. The loss of olfaction is an early change in PD, often preceding 

the onset of the classic motor symptoms. In our model, α-syn aggregate pathology 

gradually spreads along olfactory pathways, causing progressive olfactory 

deficits. We are now defining whether the deficits are due to neuronal death or to 

dysfunction in neurons that contain aggregates. 

The olfactory bulb model has been proposed to be a starting point of Lewy 

body pathology, but the initial trigger is unknown. We are currently exploring 

whether airborne environmental pollutants or other proinflammatory stimuli can 

cause α-syn aggregate pathology in the olfactory bulb. We are also examining 

immunotherapy and repurposed antidiabetic drugs for effects that reduce PD 

pathology in animal models. Given the favorable safety profile of antidiabetic agents, 

several are already being tested in PD clinical trials, but further animal trials are 

needed to understand the mechanism(s) of action. 

Our major funders include the National Institutes of Health, the Department of 

Defense, the Michael J. Fox Foundation, the Cure Parkinson’s Trust UK, and 

H. Lundbeck A/S. 



GERHARD (Gerry) A. COETZEE, Ph.D. 

Dr. Coetzee earned his Ph.D. in medical biochemistry from the University 

of Stellenbosch, South Africa, in 1977. He was a professor in the 

Departments of Urology, Microbiology, and Preventive Medicine at the Keck 

School of Medicine at USC before joining VARI as a Professor in 

November 2015. 

STAFF 

Alix Booms, B.S. 

Kim Cousineau, M.P.A. 

Steve Pierce, Ph.D. 

Trevor Tyson, Ph.D. 

J.C. Vanderschans, B.S. 


Our laboratory focuses on exploring genome-wide association studies (GWAS) to 

uncover genetic risk mechanisms in breast cancer and Parkinson’s disease (PD); 

we call these post-GWAS studies. GWAS of complex phenotypes such as those of 

breast cancer and PD have become powerful pointers to genetic predisposition. 

Additionally, as next-generation sequencing techniques have become more feasible 

and increasingly affordable, mechanisms may be explored genome-wide. A daunting 

and unexpected finding was that for many complex diseases, more than 90% of 

the risk single nucleotide polymorphisms (SNPs) are located in noncoding DNA. 

To address these issues, we and others have used chromatin biofeatures to explore 

potential functionality. 

Specifically, our laboratory uses cell culture models to probe mechanisms of risk. 

Our main hypothesis is that risk resides in enhancers scattered through our genome 

that are identifiable within chromatin biofeatures (nucleosome occupancy and 

histone covalent modifications). Enhancers are cell type–specific and mediate risk 

by specific gene expression control. For example, in one of our projects we used 

differentiating dopaminergic neurons (Lund human mesencephalic [LUHMES] cells) 

to probe PD risk enhancers. We matched the differention-specific appearance or 

disappearance of enhancers with changes in gene expression. We thus identified 

22,057 enhancers paired with 6,388 differentially expressed genes by proximity. 

These enhancers are enriched with 14 transcription factor response elements driving 

a cluster of genes involved in neurogenesis. We found that differentiated LUHMES 

cells, but not undifferentiated cells, showed enrichment for PD risk SNPs. Candidate 

genes for these loci were associated with the processes of synaptic vesicle cycling 

and transport, which implies that PD-related disruption of these pathways is 

intrinsic to dopaminergic neurons. We are using gene-editing tools to delve deeply 

into how they affect genetic predisposition. Understanding of this kind may lead to 

the identification of preventive strategies against PD. 


JEFFREY H. KORDOWER, Ph.D. 

Dr. Kordower earned his Ph.D. at City University of New York in 1984. He 

joined Rush University Medical Center in 1990, where he currently is the 

Alla V. and Solomon Jesmer Professor of Neurological Sciences and 

the director of the Rush Research Center for Brain Repair, among other 

positions. He joined VARI in January 2016 as a Professor and Director's 

Scholar while continuing his primary appointment at Rush. 


There is a close collaboration between the Kordower lab and the scientists in the 

Center for Neurodegenerative Science in trying to understand Parkinson’s disease 

pathogenesis and to develop novel therapies for the disease. Recently, the lab has 

been investigating the prion-like transfer of abnormal α-synuclein from cell to 

cell within the brain. The Kordower lab’s collaborative research program, based at 

Rush University Medical Center in Chicago, uses insights garnered from this work to 

design and carry out crucial preclinical studies, a vital step in translating potential 

therapies into clinical trials for Parkinson’s patients. 



VIVIANE LABRIE, Ph.D. 

Dr. Labrie received her Ph.D. in genetics and neuroscience from the 

University of Toronto. She was an assistant professor at University of 

Toronto before joining VARI in early 2016. 

STAFF 


Bryan Killinger, Ph.D. 

Peipei Li, Ph.D. 

Lee Marshall, Ph.D. 


Our goal is to gain an in-depth understanding of the primary molecular 

causes of Alzheimer’s disease and Parkinson’s disease in order to help develop 

new treatments. Specifically, we study epigenetic involvement in these 

neurodegenerative illnesses. Epigenetic marks such as methyl or acetyl groups 

control gene activities without changing the DNA sequence. Such marks are partially 

stable, that is, they can change in response to environmental signals and over time. 

This dynamic aspect is highly relevant, because advanced age is the best-known risk 

factor for both Alzheimer’s and Parkinson’s disease. It takes years before symptoms 

arise in patients, and after disease onset, the pathological features and symptoms 

worsen with time. We propose that aberrant epigenetic changes, accumulating with 

age at key genomic regions, contribute to the etiology of these diseases. 

We perform genome-wide searches for epigenetic abnormalities in genomic 

regulatory elements such as enhancers, which affect the complex spatial and 

temporal expression of genes. Under the influence of regulatory elements, genes 

can be highly expressed in certain tissues or cell types but weakly or not at all 

in others. By activating or repressing regulatory elements, epigenetic marks can 

modify the abundance, timing, and cell-specific patterns of gene expression, which 

are central to healthy brain function. By applying epigenomic and next generation 

sequencing–based techniques to human samples, we aim to identify epigenetically 

misregulated regulatory elements in Alzheimer’s and Parkinson’s disease. We also 

study the interaction between DNA sequence factors (SNPs) and epigenetic marks to 

determine whether certain disease-risk variants help coordinate such misregulation. 

Once we identify disturbed regulatory elements, functional studies will help us 

understand how they contribute to disease susceptibility. We look for changes 

in 3D chromatin conformation and in gene transcripts to identify the genes and 

pathways affected. We also use CRISPR-Cas9 genome editing in cell lines and mice 

to determine the contribution of epigenetically disrupted regulatory elements to 

disease pathology and symptoms. Through this research, we can uncover new 

genomic regions causally involved in Alzheimer’s and Parkinson’s disease. 


JIYAN MA, Ph.D. 

Dr. Ma earned his Ph.D. in biochemistry and molecular biology from the 

University of Illinois at Chicago. He was at Ohio State University from 2002 

until he joined VARI in November 2013 as a Professor. 

STAFF 

Romany Abskharon, Ph.D. 

Katelyn Becker, M.S. 


Amandine Roux, Ph.D. 

Juxin Ruan, Ph.D. 

Fei Wang, Ph.D. 

Xinhe Wang, Ph.D. 


Protein aggregation is a key pathological feature of a large group of late-onset 

neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Our 

overall goals are to uncover the molecular events leading to protein misfolding in 

the aging central nervous system; to understand the relationship between misfolded 

protein aggregates and neurodegeneration; and to develop approaches to prevent, 

halt, or reverse protein aggregation and neurodegeneration in these devastating 

diseases. 

We study protein aggregates in prion diseases (transmissible spongiform 

encephalopathies). These are true infectious diseases that can spread from 

individual to individual and cause outbreaks. We have established an in vitro system 

to reconstitute prion infectivity with bacterially expressed prion protein plus 

defined cofactors. We use this system to dissect the essential components and the 

structural features of an infectious prion and to uncover the molecular mechanisms 

responsible for the prion strain and species barrier. 

Recently, the concept of prions has expanded to Parkinson’s and Alzheimer’s 

diseases. α-Synuclein has been suggested to spread the disease pathology in a 

prion-like manner from a sick cell to healthy ones. We want to understand the 

similarities and differences between prions and amyloidogenic proteins such 

as α-synuclein. We are investigating cellular factors that affect α-synuclein 

aggregation and the connections between various α-synuclein aggregated forms, 

their prion-like spread, and dopaminergic neuron degeneration. 



DARREN J. MOORE, Ph.D. 

Dr. Moore earned a Ph.D. in molecular neuroscience from the University of 

Cambridge, U.K., in 2001 in the laboratory of Piers Emson. He was at Johns 

Hopkins University and the Swiss Federal Institute of Technology (EPFL) 

in Lausanne before joining the VARI faculty as an Associate Professor in 

early 2014. He was promoted to Professor in 2017. 

STAFF 

Xi Chen, Ph.D. 

Madalynn Erb, Ph.D. 


Md Shariful Islam, Ph.D. 

Jennifer Kordich, M.S. 

Nate Levine, B.S. 

An Phu Tran Nguyen, Ph.D. 

STUDENTS 

Lindsey Cunningham, B.S. 

Allie Weber, B.S. 

Erin Williams, B.A. 


Our laboratory studies the molecular pathogenesis of Parkinson’s disease, with the 

long-term goal of developing novel, targeted, disease-modifying therapies and 

neuroprotective strategies. Although most cases of PD are sporadic, 5–10% of cases 

are inherited, with causative mutations identified in at least 13 genes. We focus on 

the cell biology and pathophysiology of several proteins that cause inherited PD, 

including the dominantly inherited LRRK2 (leucine-rich repeat kinase 2, a multidomain 

protein with GTPase and kinase activity) and VPS35 (vacuolar protein 

sorting 35 ortholog, a component of the retromer complex), and the recessive 

proteins parkin (an E3 ubiquitin ligase), synaptojanin-1 (an endosomal lipid 

phosphatase), and ATP13A2 (a lysosomal P5B-type ATPase). We seek to explain 

the normal biological function of these proteins in the mammalian brain and the 

molecular mechanisms through which disease-associated variants produce neuronal 

dysfunction and eventual neurodegeneration in inherited forms of Parkinson’s. 

We employ a multidisciplinary approach that combines molecular, cellular, 

and biochemical techniques in experimental model systems such as human cell 

lines, primary neuronal cultures, Saccharomyces cerevisiae, nematodes, fruit flies, 

rodents, and human brain tissue. We have developed several unique rodent models 

(transgenic, knock-out, knock-in) for mechanistic studies of proteins. 

Some of our current projects focus on 

• the contribution of enzymatic activity and protein aggregation to 

neurodegeneration in novel, adenoviral-based, LRRK2 rodent models of PD; 

• neuroprotective effects of pharmacological kinase inhibition in LRRK2 rodent 

models; 

• genome-wide identification of genetic modifiers of LRRK2 toxicity in S. cerevisiae; 

• identification of novel GTPase effector proteins and kinase substrates for LRRK2; 

• the role of ArfGAP1 in mediating LRRK2-induced neurotoxic pathways; 

• the functional interaction of LRRK2 with other PD-linked proteins (ATP13A2 and 

synaptojanin-1); and 

• the development of novel rodent models of VPS35-linked PD and the pathological 

interactions of VPS35 with α-synuclein and LRRK2. 

Leslie Wyman, B.S. 



Amos, Christopher I., Joe Dennis, Zhaoming Wang, Jinyoung Byun, Frederick R. Schumacher, Simon A. Gayther, Graham Casey, 

David J. Hunter, Thomas A. Sellers, Stephen B. Gruber, Alison M. Dunning, . . . , Gerhard A. Coetzee, Dennis J. Hazelett, . . ., and 

Douglas F. Easton. 2017. The OncoArray Consortium: a network for understanding the genetic architecture of common cancers. 

Cancer, Epidemiology, Biomarkers & Prevention 26(1): 126–135. 

Brundin, Patrik, Kuldip D. Dave, and Jeffrey H. Kordower. 2017. Therapeutic approaches to target alpha-synuclein pathology. 

Experimental Neurology 298 (Pt. B): 225–235. 

Bryleva, E.Y., S.A. Keaton, J. Grit, Z. Madaj, A. Sauro-Nagendra, L. Smart, S. Halstead, E. Achtyes, and L. Brundin. 2017. The 

acute-phase mediator serum amyloid A is associated with symptoms of depression and fatigue. Acta Psychiatrica Scandinavica 

135(5): 409–418. 

Espay, Alberto, Patrik Brundin, and Anthony E. Lang. 2017. Precision medicine for disease modification in Parkinson disease. 

Nature Reviews Neurology 13(2): 119–126. 

Fernström, Johan, Åsa Westrin, Cécile Grudet, Lil Träskman-Bendz, Lena Brundin, and Daniel Lindqvist. 2017. Six 

autoantibodies associated with autoimmune encephalitis are not detectable in the cerebrospinal fluid of suicide attempters. 

PLoS One 12(4): e0176358. 

Islam, Md. Shariful, and Darren J. Moore. 2017. Mechanisms of LRRK2-dependent neurodegeneration: role of enzymatic activity 

and protein aggregation. Biochemical Society Transactions 45(1): 163–172. 

Jakubowski, Jennifer L., and Viviane Labrie. 2017. Epigenetic biomarkers for Parkinson’s disease: from diagnostics to 

therapeutics. Journal of Parkinson’s Disease 7(1): 1-12. 

Killinger, Bryan Andrew, and Viviane Labrie. 2017. Vertebrate food products as a potential source of prion-like α-synuclein. 

npj Parkinson’s Disease 3: 33. 

Labrie, Viviane, and Patrik Brundin. 2017. Alpha-synuclein to the rescue: immune cell recruitment by alpha-synuclein during 

gastrointestinal infection. Journal of Innate Immunity 9(5): 437–440. 

Nguyen, An Phu Tran, Guillaume Daniel, Pamela Valdés, Md Shariful Islam, Bernard L. Schneider, and Darren J. Moore. In press. 

G2019S LRRK2 enhances the neuronal transmission of tau in the mouse brain. Human Molecular Genetics. 

Nguyen, An Phu Tran, and Darren J. Moore. 2017. Understanding the GTPase activity of LRRK2: regulation, function, and 

neurotoxicity. In Leucine-rich Repeat Kinase 2 (LRRK2), Hardy J. Rideout, ed. Advances in Neurobiology series, Vol. 14. Cham, 

Switzerland: Springer, pp. 71-88. 

Oh, Edward, Richie Jeremian, Gabriel Oh, Daniel Groot, Miki Susic, KwangHo Lee, Kelly Foy, Peter W. Laird, Arturas Petronis, 

and Viviane Labrie. 2017. Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome. 

Scientific Reports 7: 41843. 

Pierce, Steven, and Gerhard A. Coetzee. 2017. Parkinson's disease-associated genetic variation is linked to quantitative 

expression of inflammatory genes. PLoS One 12(4): e0175882. 

Rey, Nolwen L., Sonia George, Jennifer A. Steiner, Zachary Madaj, Kelvin C. Luk, John Q. Trojanowski, Virginia M.-Y. Lee, and 

Patrik Brundin. In press. Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early 

neuronal loss and is reduced long term. Acta Neuropathologica. 



RECENT CENTER PUBLICATIONS (cont.) 

Tyson, Trevor, Megan Senchuk, Jason F. Cooper, Sonia George, Jeremy M. Van Raamsdonk, and Patrik Brundin. 2017. Novel 

animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein. Scientific Reports 7: 7506. 

Ventorp, Filip, Cecillie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika 

Nordström, Åsa Westrin, Patrik Brundin, and Lena Brundin. 2017. Exendin-4 treatment improves LPS-induced depressive-like 

behavior without affecting pro-inflammatory cytokines. Journal of Parkinson’s Disease 7(2): 263–273. 

Wang, Fei, Xinhe Wang, Christina D. Orrú, Bradley R. Groveman, Krystyna Surewicz, Romany Abskharon, Morikazu Imamura, 

Takashi Yokoyama, Yong-Sun Kim, Kayla J. Vander Stel, Kumar Sinniah, Suzette A. Priola, Witold K. Surewicz, Byron Caughey, 

and Jiyan Ma. 2017. Self-propagating, protease-resistant, recombinant prion protein conformers with or without in vivo 

pathogenicity. PLoS Pathogens 13(7): e1006491. 

Williams, Erin T., Xi Chen, and Darren J. Moore. 2017. VPS35, the retromer complex and Parkinson’s disease. Journal of 

Parkinson’s Disease 7(2): 219–233. 

Zamponi, Emiliano, Fiamma Buratti, Gabriel Cataldi, Hector Hugo Caicedo, Yuyu Song, Lisa M. Jungbauer, Mary J. LaDu, Mariano 

Bisbal, Alfredo Lorenzo, Jiyan Ma, Pablo R. Helguera, Gerardo A. Morfini, Scott T. Brady, and Gustavo F. Pigino. 2017. Prion 

protein inhibits fast axonal transport through a mechanism involving casein kinase 2. PLoS One 12(12): E0188340. 


Differentiation of LUHMES cells as a model of human substantia nigra neurons. These human 

neural precursor cells were immortalized using a Myc oncogene in a Tet-off system; adding tetracycline 

suppresses the expression of the Myc gene and allows differentiation to occur. Differential interference 

contrast (DIC) micrographs (100X) of A) undifferentiated LUHMES cells and B) LUHMES cells after 6 days 

of differentiation. Images by Trevor Tyson of the Coetzee laboratory. 


Core Technologies and Services 

Van Andel Research Institute’s Core Technologies 

and Services offer a comprehensive range of 

advanced technologies and expertise to support 

and enhance the research done at the Institute 

and with collaborating organizations. 


Staining of mouse bone to visualize bone marrow (red cells), solid bone with embedded 

osteocytes (tan areas), and regions of actively growing new bone (blue-green). 

Image by Alexis Bergsma.

Genomics Core 

MARIE ADAMS, M.S. 

Ms. Adams earned an M.S. in genetics from Iowa State University and is 

an expert in the latest next-generation sequencing techniques. She joined 

VARI in September 2016 from the University of Wisconsin Biotechnology 

Center, where she managed the next-generation sequencing core. 

SERVICES 

The Genomics Core provides a comprehensive catalog of sequencing, genotyping, 

and cytogenetic services to support research into the genomic, transcriptomic, 

and epigenomic bases of diseases such as cancer and neurodegenerative disorders. 

Core staff collaborate with over 45 VARI and external investigators to design and 

implement robust protocols and experimental design. 

STAFF 

Julie Koeman, B.S., C.G.(ASCP) CM 

Lori Moon, E.M.B.A. 

Mary Rhodes, B.S. 

STUDENT 

Sarah Harrie 

Sequencing services offered include whole-genome, exome, and targeted DNA 

sequencing; mRNA expression, total RNA transcriptome, translatome, and targeted 

RNA sequencing; and ChIP-seq, methyl-seq, whole-genome bisulfite sequencing, 

and targeted bisulfite sequencing, all using Illumina sequencing platforms. 

Additionally, single-cell and long-read sequencing are facilitated through the 10X 

Genomics Chromium system. We constantly evaluate new assays to provide the most 

up-to-date service in this evolving field. 

High-throughput genotyping services are performed using the Illumina iScan 

system and include the MethylationEPIC Array, Omni-series genome and 

exome arrays, Neuro Consortium array, and QC array. Other arrays are easily 

accommodated on request. We are also available for qPCR and SNP assays. 

Cytogenetic capabilities include FISH probe creation, validation, and analysis; 

chromosome breakage studies; transgene localization; and trisomy 8 and 11 mouse 

embryonic stem cell screens. 


Bioinformatics and Biostatistics Core 

MEGAN BOWMAN, Ph.D. 

Dr. Bowman earned her Ph.D. from the University of Wisconsin – Madison. 

She completed postdoctoral research in genomics and bioinformatics 

with the United States Department of Agriculture and Michigan State 

University prior to joining VARI in 2016. 

SERVICES 

Established in April 2013, the Bioinformatics and Biostatistics Core serves the 

analytical needs of VARI by providing high-quality computational and statistical 

support to the research laboratories. The broader mission of the BBC is to strengthen 

and advance bioinformatics and biostatistics at VARI through collaboration, 

education, and methods development. 

STAFF 

Benjamin Johnson, Ph.D. 

Zachary Madaj, M.S. 


* Mary E. Winn, Ph.D. 

Emily Wolfrum, M.P.H. 

* Formerly manager of the BBC, now 

Program Manager in the Office of the Cores. 

The BBC provides statistical consulting and experimental design, including sample 

size determination and randomization procedures, and we analyze a wide variety 

of data related to next-generation sequencing, such as genomic variant detection 

and annotation, differential expression, DNA copy number determination, and 

differential methylation analyses. We offer expertise in systems-level analysis, 

including gene-set and network-based analyses, time-series data, tumor growth, 

drug response, and other small or large data sets using appropriate statistical 

and computational methods. We also assist in the preparation of research grants, 

manuscripts, and data deposition. The Core focuses on reproducibility and rigor via 

robust statistical design, analysis, and the maintenance of version-controlled source 

code. 

We support the greater educational mission of the Institute, helping students 

and staff develop an analytic approach and skills in experimental design through 

seminars, lectures, and workshops. 


Vivarium and Transgenics Core 

BRYN EAGLESON, M.S., LATG 

Ms. Eagleson earned an M.S. degree in laboratory animal science from 

Drexel University’s College of Medicine. She worked for many years at the 

National Cancer Institute’s Frederick Cancer Research and Development 

Center in Maryland before joining VARI as the Director of Vivarium and 

Transgenics in 1999. 

SERVICES 

The goal of the VARI Vivarium and Transgenics Core is to develop, provide, and 

maintain high-quality mouse modeling services. The vivarium is a state-of-the-art 

facility that includes a high-level containment barrier. Van Andel Research Institute 

is an AAALAC-accredited institution, most recently reaccredited in November 

2016. All procedures are conducted according to the Guide for the Care and Use of 

Laboratory Animals. The staff provides rederivation, surgery, dissection, necropsy, 

breeding, weaning, tail biopsies, sperm and embryo cryopreservation, animal data 

management, project management, and health-status monitoring. Transgenic 

mouse models are produced on request for project-specific needs. The creation of 

gene-targeted mice using the CRISPR/Cas9 system has been implemented. We also 

provide therapeutic testing and preclinical model development services. Projects 

include pharmacological testing, target validation testing, patient-derived xenograft 

(PDX) development, orthotopic engraftment model development, and subcutaneous 

xenograft/allograft model development. 

The Small-Animal Imaging Facility provides preclinical imaging technologies that 

offer anatomic and functional information to biomedical investigators. Currently 

available technologies include high-resolution microCT, micro-ultrasound, and 

optical imaging. 

STAFF 

Megan Briggs, B.S. 

Brandon Bonnema, B.S. 

Stephen Bowman, M.S. 

Charles Bradfield, B.S. 

Rita Burdette 

Thomas Dingman, B.S. 

Nicholas Getz, B.S. 

Sara Greenwald, B.S. 

Audra Guikema, B.S., LVT 

Tristan Kempston, B.S. 

Tina Meringa, A.A. 

David Monsma, Ph.D. 


Malista Powers, A.S., LVT 

Mathew Rackham 

Lisa Ramsey, A.S., LVT 

Adam Rapp, B.S. 

Yanli Su, A.M.A.T. 

Aurora Thoms, A.S. 

Collin Tidd, A.S. 

William Weaver, B.S. 


Confocal Microscopy and Quantitative Imaging Core 

CORINNE ESQUIBEL, Ph.D. 

Dr. Esquibel has a B.S. in biology from Truman State University and a 

Ph.D. in molecular and cellular pharmacology from the University of 

Wisconsin–Madison. She joined Van Andel Research Institute as the Core 

manager in 2017. 

SERVICES 

Established in October 2013, the Core provides optical imaging services for Van Andel 

Research Institute and collaborating institutions. We focus on comprehensive training 

of users for every aspect of imaging: experimental design and optimization, data 

acquisition, and image analysis. This helps users of all experience levels to perform 

quantitative research at or exceeding the professional standards of their field. To do 

this, we maintain multiple instruments with a range of imaging capabilities. 

STAFF 

Kristin Feenstra, B.S. 


A Nikon A1plus laser scanning confocal is an essential instrument within the Core, 

designed to generate high-resolution images in multiple dimensions. It is equipped 

for imaging in both galvanometric and resonant scanning modes with four solid state 

lasers, four high-sensitivity detectors, and a multi-anode spectral detector. The 

confocal can achieve optical sectioning of cells and tissue and can image live samples 

over time. The computer-coded stage allows for imaging large areas of the sample. 

The PerkinElmer Vectra 3.0 Automated Quantitative Pathology Imaging system is 

capable of imaging up to 200 slides per session, using a sophisticated multispectral 

camera to mathematically unmix up to seven fluorophores in each slide. Trainable 

algorithms in the PerkinElmer inForm software allow for automated segmentation 

and quantitative phenotyping of slides. 

Image analysis is supported not only through consultation and training of users, but 

also through the availability of a powerful Silicon Mechanics PC workstation that 

contains a suite of commercial and open-source image analysis programs. Analysis 

options include 3D-5D visualization (FIJI, Nikon Elements, Imaris), deconvolution 

(Huygens Professional), neuron tracing (Imaris), segmentation (Imaris, MATLAB), 

machine learning (CellProfiler and CPAnalyst), and figure preparation (FIJI/Image J, 

Illustrator, Photoshop). When out-of-the-box solutions are not available, additional 

sophisticated mathematical analysis can be written for case-specific applications 

(MATLAB). 


Pathology and Biorepository Core 

SCOTT D. JEWELL, Ph.D. 

Dr. Jewell earned his Ph.D. degree from The Ohio State University. 

He joined VARI in 2010 as a Professor, Director of the Program for 

Technologies and Cores, and Director of the Pathology and Biorepository 

Core. 

STAFF 

Bree Berghuis, B.S., HTL(ASCP), QIHC 

Alex Blanski, B.S. 

Melissa Dehollander, M.B.A., B.S. 

Brianne Docter, M.S. 

Kristin Feenstra, B.S. 

Phil Harbach, M.S. 

Meghan Hodges, B.S. 

Galen Hostetter, M.D. 

Eric Hudson, B.S. 

Carrie Joynt, B.S., HT 

Rob Montroy, B.S. 


Chelsea Peterson, B.S. 

Daniel Rohrer, B.S., M.B.A. 

Lisa Turner, B.S., HT, QIHC(ASCP) 

SERVICES 

The Pathology and Biorepository Core integrates anatomic pathology expertise with 

biorepository and biospecimen science in order to assist in VARI’s research. We build upon 

historical strengths in standard histology, microscopy, and biobanking, and we apply 

best practices in biospecimen science. The pathology discipline provides complementary 

emphasis on high-quality biospecimens and interpretable results with which to validate 

experimental models and extend them to clinical samples, thereby advancing our common 

translational mission. The VARI Biorepository has been accredited by the College of 

American Pathologists (CAP) since 2012. Dr. Jewell serves as a committee member for the 

CAP Biorepository Accreditation Program. 

Dr. Jewell, with his experience in clinical trials and biobanking, and Dr. Hostetter, who is 

board-certified in anatomic pathology, are currently studying the effects of preanalytical 

variables in tissue collection and transport on the integrity of downstream analytes. 

The Core provides assessment of tumor suppressors and immunomodulators in tumor 

tissues and the application of genomic and epigenomic assays for biospecimens. The 

VARI biorepository is nationally and internationally recognized, serving as the NCI 

Comprehensive Biospecimen Resource for the Genotype-Tissue Expression Program 

(GTEX). In 2015, it was designated as the Biorepository Core Resource for the NCI Clinical 

Proteomic and Tumor Analysis Consortium (CPTAC) and as the biorepository for the 

Tuberous Sclerosis Alliance. In addition, we are moving into our seventh year of providing 

biorepository services for the Multiple Myeloma Research Foundation’s CoMMpass Study. 

The biorepository is serving the VARI-SU2C consortium for epigenetics clinical trials 

biobanking, collaborating with Drs. Jones and Baylin. 

Pathology Core services 

• Histology and diagnostic tissue services, including morphology, 

immunohistochemistry, in situ hybridization, and multiplex fluorescent IHC assays 

• Pathology review and annotation of clinical samples from VARI’s prospective and 

retrospective tissue collections 

• Design and construction of tissue microarrays 

• Digital imaging and spectral microscopy coupled with image analysis tools 

• Cell fractionation and biospecimen processing 

• Laser capture microdissection 

Biorepository Core services 

• Biospecimen kit construction, shipping, and tracking 

• Clinical trials biobanking coordination 

• Quality management program 

Dana Valley, B.A., ASQ CMQ/OE, CSSGB 

Anthony Watkins, A.S. 


Flow Cytometry Core 

RACHAEL SHERIDAN, Ph.D. 

Rachael Sheridan earned her Ph.D. in biochemistry from the University 

of Wisconsin–Madison and also holds a professional cytometry 

certification, SCYM(ASCP). Prior to joining Van Andel Research Institute in 

October 2016, she was an instrumentation specialist in the University of 

Wisconsin Comprehensive Cancer Center Flow Cytometry Laboratory. 

STAFF 


SERVICES 

The Core provides comprehensive flow cytometry analysis and sorting services 

in support of VARI research. Additional services include assistance with protocol 

development and training in data analysis. Flow cytometry services are provided 

using a Beckman Coulter MoFlo Astrios and Beckman Coulter CytoFLEX S. Available 

hematology equipment includes a VetScan instrument, a VetScan HMII, and a 

Shandon Cytospin 3. 

Kellie Sisson, B.S. 


Cryo-Electron Microscopy Core 

GONGPU ZHAO, Ph.D. 

Dr. Zhao earned his Ph.D. in physics at the University of North Carolina at 

Chapel Hill. He joined Van Andel Research Institute in 2016 as manager of 

the Cryo-EM Core. 

STAFF 

Xing Meng, Ph.D. 


SERVICES 

Project 1. During replication initiation, the core component of the helicase—the 

Mcm2-7 hexamer—is loaded on the origin DNA as a double hexamer. Determining 

how the origin DNA interacts with the axial channel could provide key insights into 

Mcm2-7 function and regulation. We worked with Huilin Li’s lab to solve a 3.9-Å 

cryo-EM structure of the Mcm2-7 double hexamer on DNA, which suggests a laggingstrand 

DNA extrusion model. 

Project 2. G protein–coupled receptor (GPCR) kinases (GRKs) play key roles in the 

desensitization of GPCR signaling. Dysregulation of this process has been associated 

with a broad spectrum of diseases. The overall goal of this project is to use rhodopsin– 

GRK1 as a model in order to gain structural insight into the GPCR/GRK complex and 

its mechanism of GRK-mediated GPCR signaling. We have worked with the Xu lab to 

reveal the overall architecture of the rhodopsin–GRK1 complex via negative-stain EM. 

Our plans are to use cryo-EM to solve the structure of the complex at high resolution. 

Project 3. G protein–coupled receptors are a superfamily of integral membrane 

proteins that turn extracellular signals into intracellular responses. The selective 

coupling of GPCRs to specific G proteins is crucial for activating the appropriate 

physiological response. With the help of state-of-the-art electron microscopy at VARI, 

the Core has worked with the Xu lab to determine a 4-Å structure of the rhodopsin–G i 

complex, giving the first insights into G i 

-mediated GPCR activation. This research also 

established a general method for studying GPCR structures in an active confirmation 

and will provide guidance for new-generation, biased drug designs that can specifically 

trigger beneficial effects and avoid side effects. This work has significant influence on 

both basic biological research and translational studies. 


RECENT CORE PUBLICATIONS 

Barnett, Daniel, Ying Liu, Katie Partyka, Ying Huang, Huiyuan Tang, Galen Hostetter, Randall E. Brand, Aatur D. Singhi, Richard 

R. Drake, and Brian B. Haab. 2017. The CA19-9 and sialyl-TRA antigens define separate subpopulations of pancreatic cancer 

cells. Scientific Reports 7: 4020. 

Berger, Penny L., Mary E. Winn, and Cindy K. Miranti. 2017. Miz1, a novel target of ING4, can drive prostate luminal epithelial 

cell differentiation. Prostate 77(1): 45–59. 

Dues, Dylan J., Claire E. Schaar, Benjamin K. Johnson, Megan J. Bowman, Mary E. Winn, Megan M. Senchuk, and Jeremy M. 

Van Raamsdonk. 2017. Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in 

Caenorhabditis elegans. Free Radical Biology and Medicine 108: 362–373. 

He, Yuanzheng, Xiang Gao, Devrishi Goswami, Li Hou, Kuntal Pal, Yanting Yin, Gongpu Zhao, Oliver P. Ernst, Patrick Griffin, 

Karsten Melcher, and H. Eric Xu. 2017. Molecular assembly of rhodopsin with G protein–coupled receptor kinases. Cell Research 

27(6): 728–747. 

Manojlovic, Zarko, Austin Christofferson, Winnie S. Liang, Jessica Aldrich, Megan Washington, Shukmei Wong, Daniel Rohrer, 

Scott Jewell, Rick A. Kittles, Mary Derome, Daniel Auclair, David Wesley Craig, Jonathan Keats, and John D. Carpten. 2017. 

Comprehensive molecular profiling of 718 multiple myelomas reveals significant differences in mutation frequencies between 

African and European descent cases. PLoS Genetics 13(11): e1007087. 

Martin, Katie R., Wanding Zhou, Megan J. Bowman, Juliann Shih, Kit Sing Au, Kristin E. Dittenhafer-Reed, Kellie A. Sisson, Julie 

Koeman, Daniel J. Weisenberger, Sandra L. Cottingham, Steven T. DeRoos, Orrin Devinsky, Mary E. Winn, Andrew D. Cherniack, 

Hui Shen, Hope Northrup, Darcy A. Krueger, and Jeffrey P. MacKeigan. 2017. The genomic landscape of tuberous sclerosis 

complex. Nature Communications 8: 15816. 

Noguchi, Yasunori, Auanning Yuan, Lin Bai, Sarah Schneider, Gongpu Zhao, Bruce Stillman, Christian Speck, and Huilin Li. 2017. 

Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proceedings of the 

National Academy of Sciences U.S.A. 114(45): E9529–E9538. 

Westrick, Randal J., Kärt Tomberg, Amy E. Siebert, Guojing Zhu, Mary E. Winn, Sarah L. Dobies, Sara L. Manning, Marisa A. 

Brake, Audrey C. Cleuren, Linzi M. Hobbs, Lena M. Mishack, Alexander J. Johnston, Emilee Kotnik, David R. Siemieniak, Jishu 

Xu, Jun Z. Li, Thomas L. Sauders, and David Ginsburg. 2017. Sensitized mutagenesis screen in Factor V Leiden mice identifies 

thrombosis suppressor loci. Proceedings of the National Academy of Sciences U.S.A. 114(36): 9659–9664. 


Awards for Scientific Achievement 


Jay Van Andel Award for Outstanding 

Achievement in Parkinson’s Disease 

Research 

The Jay Van Andel Award for Outstanding Achievement in Parkinson’s Disease 

Research was established in 2012 in memory of Van Andel Institute founder 

Jay Van Andel, who battled Parkinson’s disease for a decade before his death in 

2004. The award is given to scientists who have made outstanding contributions to 

Parkinson’s disease research and who have positively impacted human health. 

2017 RECIPIENT 

J. William Langston, M.D. 

Dr. J. William Langston is the Scientific Director, Chief Scientific Officer, and Founder 

of the Parkinson’s Institute in Sunnyvale, California. Dr. Langston gained international 

recognition in 1980s for the discovery of the link between a tainted synthetic heroin 

and parkinsonism. The discovery of the biologic effects of that compound led to a 

renaissance of basic and clinical research into Parkinson’s disease. Dr. Langston’s 

current research includes the study of mechanisms of neuronal degeneration, the 

etiology of Parkinson’s disease, the development of new strategies to slow or halt 

disease progression, and ways to identify the disease in its earliest “pre-motor” stages. 

PRIOR RECIPIENTS 

2016—Stanley Fahn, M.D. 

2015—Robert Nussbaum, M.D., and Maria Grazia Spillantini, Ph.D., FMedSci, FRS 

2014—Andrew John Lees, M.D., FRCP, FMedSci 

2013—Alim-Louis Benabid, M.D., Ph.D. 

2012—Andrew Singleton, Ph.D. 


Awards for Scientific Achievement 

Han-Mo Koo Memorial Award 

Dr. Han-Mo Koo joined Van Andel Research Institute in 1999 as one of its founding 

investigators, focusing on the identification of genetic targets for anti-cancer drug 

development against melanoma and pancreatic cancer. In May 2004, Dr. Koo passed 

away following a six-month battle with cancer. To honor his memory and scientific 

contributions, the Han-Mo Koo Memorial Award was established in 2010. Awardees 

are selected based on scientific achievements, peer recognition, and that their 

contributions to human health and research align with the scientific legacy of 

Han-Mo Koo. 

2017 RECIPIENT 

James P. Allison, Ph.D. 

Dr. Allison is a professor and the chair of the Department of Immunology at the 

University of Texas MD Anderson Cancer Center. His fundamental discoveries include 

the definition of the structure of the T cell antigen receptor and the demonstration 

that CTLA-4 is an inhibitory checkpoint that inhibits activated T cells. He proposed 

that immune checkpoint blockade might be a powerful strategy against many cancer 

types and conducted preclinical experiments showing its potential. His development of 

the concept of immune checkpoint blockade has transformed cancer therapy and saved 

thousands of lives. 

PRIOR RECIPIENTS 

2016—Matthew L. Meyerson, M.D., Ph.D. 

2015—Eric Lander, Ph.D. 

2013—Frank P. McCormick, Ph.D., F.R.S. 

2012—Phillip A. Sharp, Ph.D. 


Tom Isaacs Award 

The Tom Isaacs Award is given jointly by Van Andel Research Institute and The Cure 

Parkinson’s Trust. The award was established in memory of Trust co-founder and 

champion of the Parkinson’s community Tom Isaacs, who passed away in 

May 2017. This award recognizes his vision that a cure for Parkinson’s can and will 

be found, but that greater value will be gained from working with people who have 

Parkinson’s in this quest. In that spirit, recipients of the award must have had a 

significant impact on the lives of people with Parkinson’s or have involved people 

with Parkinson’s in a participatory way in their work. 

Inaugural Recipient 

Thomas Foltynie, B.Sc., MBBS, MRCP, Ph.D. 

Dr. Foltynie is a consultant neurologist at University College London. He trained 

in medicine at UCL, and he undertook his Ph.D. in Cambridge where he studied the 

heterogeneity of Parkinson's disease. He is the senior author of a groundbreaking 

study that shows the diabetes drug exenatide may interfere with Parkinson’s 

progression, something no current medication can do. 


Educational and Training Programs 


Van Andel Institute Graduate School 

STEVEN J. TRIEZENBERG, Ph.D. 

President and Dean 

Van Andel Institute Graduate School develops future leaders in biomedical research 

through an intense, problem-focused Ph.D. degree in cellular, molecular, and 

genetic biology. VAIGS has created an innovative curriculum that guides doctoral 

students to think and act like research leaders through problem-based learning. In 

doing so, students develop key skills of finding and evaluating scientific knowledge 

and of designing experimental approaches to newly arising questions. We also foster 

the development of leadership skills and professional behavior, and we seek to 

integrate graduate students into the professional networks and culture of science. 

VAIGS currently has 27 students. The most recent cohort of seven includes two 

international students. In the past year, five students defended their dissertations 

and completed their Ph.D. degrees. VAIGS alumni have gone on to postdoctoral and 

professional positions at leading biomedical research institutions and companies 

throughout the United States. VAIGS is accredited by the Higher Learning 

Commission (www.hlcommission.org; 1-800-621-7440). 

Julie Davis Turner, Ph.D., Associate Dean 

Kathy Bentley, B.S. 

Patty Farrell-Cole, Ph.D. 

Michelle Love, M.A. 

Christy Mayo, M.A. 

Susanne Miller-Schachinger, B.B.A. 

Nancy Schaperkotter, A.M., LCSW, CEAP 


VAIGS Graduate Students 

The following students were enrolled in VAIGS in 2017. 

Menusha Arumugam 

University of Michigan–Flint 

First-year student 

Aditi Bagchi, M.D. 

Kasturba Medical College, 

Mangalore, India 

MacKeigan/Jewell labs 

Alexis Bergsma 

University of Michigan, Ann Arbor 

Miranti/Williams labs 

Maggie Chassé 

Colorado State University, Fort Collins 

Grohar lab 

Wooyoung Choi 

Tsinghua University, Beijing, China 

Lü lab 

Jason Cooper 

University of Texas at Austin 

Van Raamsdonk lab (Ph.D., 2017) 

Eric Cordeiro-Spinetti 

Instituto Federal de Educação, Ciência e 

Tecnologia do Rio de Janeiro, Brazil 


Lindsey Cunningham 

Northern Arizona University, Flagstaff 

Moore lab 

Zachary DeBruine 

Hope College, Holland, Michigan 

Melcher lab 

Parker de Waal 

Kalamazoo College, Michigan 

Xu lab 

Minge Du 

Ludong University, Yantai, China 

H. Li lab 

Jamie Endicott 

Michigan State University, East Lansing 


Guillermo Flores 


Grohar lab 

Jamie Grit 


Steensma lab 

Emily Haley 

University of Alabama at Birmingham 


Candace King 

Tougaloo College, Mississippi 

Steensma lab 

Katie Krajnak 

Purdue University Calumet, 

Hammond, Indiana 

Williams lab 

Emily Machiela 

Grand Valley State University, 

Allendale, Michigan 

Van Raamsdonk lab 

Lauren McGee 

Hanover College, Indiana 


Kevin Maupin 



Williams lab (Ph.D., 2017) 

Nathan Merrill 


MacKeigan lab (Ph.D., 2107) 

Eric Nollett 

Calvin College, 

Grand Rapids, Michigan 

Miranti lab (Ph.D., 2017) 

Jordan Prahl 




Abbey Solitro 

Ferris State University, 

Big Rapids, Michigan 

MacKeigan lab 

Nicole Thellman, D.V.M. 

Louisiana State University, Baton Rouge 

Triezenberg lab (Ph.D., 2017) 

Bailey Tibben 

University of Arizona, Tucson 


Nicole Vander Schaaf 

Indiana Wesleyan University, 

Marion, Indiana 

Laird lab 

Robert Vaughan 



Rothbart lab 

Allie Weber 


Moore lab 

Erin Williams 

Anderson University, Indiana 

Moore lab 

Leslie Wyman 



Moore lab 


Summer Internship Program 

The VARI summer internships are designed to provide undergraduate students to opportunities be mentored 

by professionals in biomedical research, to use state-of-the-art scientific equipment, and to learn valuable 

interpersonal, workplace, and presentation skills. The goal of this program is to expose aspiring researchers 

and clinicians to exciting advances in biomedical science that will help them define their career paths. 

Internships last 10 weeks, with two cohorts per summer. Van Andel Education Institute partners with the United 

Negro College Fund to match students interested in biomedical research careers with summer internships 

at VARI. 

Since 2001, hundreds of VARI internships have been generously supported through the Frederik and Lena Meijer 

Summer Internship Program. Meijer interns are noted in the listing below by an asterisk (*). 

Calvin College, Grand Rapids, Michigan 

*Brianna Busscher (Szabo) 

*Rachel House (Wu) 

*Lucas VanLaar (Melcher) 

*Mark Wolf (MacKeigan) 

Boston College, Massachusetts 

Catherine VanderWoude (Business 

Development) 

Central Michigan University, 

Mt. Pleasant 

*Matthew Fini (Li) 

Cheyann Oliver (Purple Community) 

Claflin University, Orangeburg, South 

Carolina 

Ricardo Burke (Haab) 

Lowell High School, Michigan 

Corah Kaufman (Van Raamsdonk) 

Ferris State University, Big Rapids, 

Michigan 

Drew Eder (Facilities) 

Sarah Harrie (Genomics) 

*Courtney Wernette (Grohar) 

Maria Winquest (VAIGS) 



Sudakshina Chakrabarty (Sempere) 

Jessica DeWyse (Finance) 

Johnathan Hall (Haab) 

Delaney McCarrey (Purple Community) 

Hillsdale College, Michigan 

*Christine Ausherman (Rothbart) 

*Madison Frame (Triezenberg) 

*Taylor Zimmer (Ma) 


Jessica (Jess) Guillaume (MacKeigan) 

Philip Versluis (Rothbart) 

Indiana Wesleyan University, Marion 

*Hannah VanDusen (Haab) 

Innovation High School, Grand Rapids, 

Michigan 

Angelica Velasquez (Jovinge) 


*Joyce Goodluck (Sempere) 

*Brandt Gruizinga (Labrie) 

*Zachary Jansen (Laird) 

*Yamini Vepa (Labrie) 

*Yuk Kei Wan (Yang) 

Michigan Technological University, 

Houghton 

*Carly Joseph (Van Raamsdonk) 

Rosalind Franklin University, Chicago, 

Illinois 

Marie Mustert (Jewell) 

Stony Brook University, New York 

Calvin Li (Information Technology) 

University of Alabama - Huntsville 

*Sean Zhou Morash (Xu) 

University of Chicago, Illinois 

Michelle Zhang (Moore) 


Schyler Bennett (Haab) 

Adrienne (Denise) Bilbao (Yang) 

*Kate Blumenstein (Li) 

*Nolan Klunder (Jovinge) 

*Adam Racette (Williams) 

*Nolan Redetzke (Williams) 

Western Michigan University, 

Kalamazoo 

*Megan Callaghan (Steensma) 


Postdoctoral Fellowship Program 

Van Andel Research Institute provides postdoctoral training opportunities to advance the knowledge and 

research experience of new Ph.D.s while at the same time supporting our research endeavors. Each fellow is 

assigned to a scientific investigator who oversees the progress and direction of research. Fellows who worked in 

VARI laboratories in 2017 are listed here. 

Walid Abi Habib 

Université Pierre et Marie Curie, 

Paris, France 

Laird lab 

Romany Abskharon 

Vrije Universitiet Brussel, Belgium 

Ma lab 

Brittany Carpenter 

University of Kentucky, Lexington 

Jones lab 

Xi Chen 

University of Liverpool, United Kingdom 

Moore lab 

Evan Cornett 

University of Central Florida, Orlando 

Rothbart lab 

Madalynn Erb 

Oregon Health and Science University, 

Portland 

Moore lab 

Chen Fan 

Institute for Nutritional Sciences, 

Shanghai, China 

Du lab 

Huihui Fan 

Harbin Medical University, China 

Shen lab 

Xiang Feng 

Baylor College of Medicine, Waco, Texas 

H. Li lab 

Sourik Ganguly 

University of Kentucky, Lexington 

X. Li lab 

Yihe Huang 

Peking University, China 

Lü lab 

Zhijun Huang 

Harbin Institute of Technology, China 

Pfeifer lab 

Md Shariful Islam 

Max Planck Institute for Heart and Lung 

Research, Bad Neuheim, Germany 

Moore lab 

Manpreet Kalkat 

University of Toronto, Canada 

Laird lab 

Bryan Killinger 

Wayne State University, 

Detroit, Michigan 

Labrie lab 

Alison Lanctot 

Northwestern University, 

Evanston, Illinois 

Rothbart lab 

Hua Li 

Guangzhou Institutes of Biomedicine 

and Health, China 

H. Li lab 

Jianshuang Li 

Wuhan University, China 

Yang lab 

Peipei Li 

Chungbuk National University, 

Cheongju, South Korea 

Labrie lab 

Hongbo Liu 


Shen lab 

Lee Marshall 

Garvan Institute of Medical Research, 

Sydney, Australia 

Labrie lab 

Xiangqi Meng 

Sun Yat-sen University Cancer Center, 

Guangzhou, China 

X. Li lab 

Megan Michalski 


Williams lab 

John Murdoch 

Yale University, New Haven, Connecticut 

Labrie lab 

An Phu Tran Nguyen 

University of Tübingen, Germany 

Moore lab 

Hitoshi Otani 

Tokyo Medical and Dental University, 

Japan 

Jones lab 

Kuntal Pal 

National University of Singapore, 

Singapore 

Xu lab 

Wouter Peelaerts 

Katholieke Universiteit Leuve, Belgium 

P. Brundin lab 


Steven Pierce 

Columbia University, 

New York, New York 

Coetzee lab 

Tinghai Xu 

Shanghai Institute of Materia Medica, 

China 

Jones lab 

Emmanuel Quansah 

De Montfort University, 

Leicester, United Kingdom 


Yanting Yin 

Shanghai Institute of Materia Medica, 

China 

H. Li lab 

Nolwen Rey 

University of Lyon, France 


Tie-bo Zeng 


Szabó lab 

Amandine Roux 

University Pierre and Marie Curie, 

Paris, France 

Ma lab 

Wanding Zhou 

Rice University, Houston, Texas 

Shen lab 

Juxin Ruan 

Shanghai Institute for Biological 

Sciences, China 

Ma lab 

Rajamani Keerthi Thirtamara 

Ohio State University, Columbus 

L. Brundin lab 

Rochelle Tiedemann 

Georgia Regents University, Augusta 

Rothbart lab 

Elizabeth Tovar 

Wayne State University, 

Detroit, Michigan 

Steensma lab 

Zhi-Qiang Wang 

Laval University, 

Quebec City, Canada 

Pfeifer lab 

Laura Winkler 

University of Wisconsin, Madison 

Jovinge lab 

Paige Winkler 


Lü lab 


Organization 


Primary cortical neurons of a rat. Staining is for Map2 (red), a protein found in neural dendrites, 

and sortilin (green), a neural receptor typically found in endosomes. DAPI stains the cell nuclei blue. 

The large cell to the upper left that has no dendrites is likely an astrocyte. 

Image by Erin Williams of the Moore laboratory. Copyright MBF Bioscience; used with permission.

Management 

VARI Board of Trustees 

David L. Van Andel, Chairman 

Tom R. DeMeester, M.D. 

James B. Fahner, M.D. 

Michelle M. Le Beau, Ph.D. 

George F. Vande Woude, Ph.D. 

Ralph Weichselbaum, M.D. 

Max S. Wicha, M.D. 

DAVID L. VAN ANDEL 

Chairman and CEO Van Andel Institute 

Board of Scientific Advisors 

The Board of Scientific Advisors advises the 

CEO and the Board of Trustees, providing 

recommendations and suggestions regarding the 

overall goals and scientific direction of VARI. 

The members are 

Michael S. Brown, M.D., Chairman 

Richard Axel, M.D. 

Joseph L. Goldstein, M.D. 

Tony Hunter, Ph.D. 

Phillip A. Sharp, Ph.D. 


PETER A. JONES, Ph.D., D.Sc. 

Chief Scientific Officer 

PATRIK BRUNDIN, M.D., Ph.D. 

Associate Director 

Office of the Chief Scientific Officer 

Aubrie Bruinsma, B.A., Events and Meetings Coordinator 

Ryan Burgos, B.S., Clinical Research Analyst 

David Cabrera, M.S., Chief of Staff 

Kayla Habermehl, B.A., B.S., Science Communications Specialist 

Jennifer Holtrop, B.S., Research Operations Coordinator 

Chelsea John, B.S., Research Department Administrator 

David Nadziejka, M.S., E.L.S., Science Editor 

Aaron Patrick, B.S., Research Operations Supervisor 

External Scientific Advisory Board 


Marie-Françoise Chesselet, M.D., Ph.D. 

Sharon Y.R. Dent, Ph.D. 

Howard J. Federoff, M.D., Ph.D. 

Theresa Ann Guise, M.D. 

Kristian Helin, Ph.D. 

Rudolf Jaenisch, Ph.D. 

Max S. Wicha, M.D. 

Bonnie Petersen, Executive Assistant 

Beth Resau, B.A., M.B.A., Scientific Events and Meetings Supervisor 

Daniel Rogers, B.S., CCRC, CIP, Clinical Research Manager 

Veronique Schulz, B.S., Research Operations Coordinator 

Stephanie Stewart, B.S., Senior Administrative Assistant 


Administrative Departments 

The departments listed below provide administrative support to both the Van Andel Research Institute and the 

Van Andel Education Institute. 

Executive 

David Van Andel, Chairman and CEO 

Christy Goss, Senior Executive Assistant 

Operations 

Jana Hall, Ph.D., M.B.A., 

Chief Operations Officer 

Ann Schoen, Senior Executive Assistant 

Business Development and 

Extramural Administration 

Thomas DeKoning, Director 

Robert Garces, Ph.D. 

Andrea Poma, M.P.A. 

Christine Timbol, B.A., M.A. 

Compliance 

Gwenn Oki, Director 

Jessica Austin 

Angie Jason 

Laura Kersjies 

Dave Lutkenhoff 

Communications and Marketing 

Beth Hinshaw Hall, Director 

Frank Brenner 

Alex Edema 

Rachel Harden 

Caitlin Smith 

Development 

Brett Holleman, 

Chief Development Officer 

Patrick Placzkowski, Director 

Hannah Acosta 

Betty Alexander 

Maddie Eaton 

Allyson Huttenga 

Ashley Owen 

Teresa Reid 

Sarah Rollman 

Lawrence Rush 

Angie Stumpo 

Facilities 

Samuel Pinto, Director 

Beau Burnett, Chef 

Jeff Cooling, Manager 

Jeff Wilbourn, Manager 

Tim Bachinski 

Maria Becerra-Mota 

Dedefo Bedaso 

Nuritu Bedaso 

Rob Cairns 

Hebib Chakeri 

Jessica Copley 

Deb Dale 

Jason Dawes 

Lupe Delgado 

Ken DeYoung 

Art Dorsey 

Kristi Gentry 

Tammy Humphreys 

Hodilia Jimenez 

Matthew Jump 

Todd Katerburg 

Tracy Lewis 

Lewis Lipsey 

Micah McNeil 

Dave Marvin 

Kristina Mason 

Jeannette Mendez 

Amanda Miller 

Joan Morrison 

Jamison Pate 

Karen Pittman 

Amber Ritsema 

Tyler Rosel-Pieper 

Kristina Schaner 

Amber TenBrink 

Dalu Tibesso 

Rich Ulrich 

Pete Van Conant 

Finance 

Timothy Myers, 

Vice President and Chief Financial Officer 

Katie Helder, Controller 

Rich Herrick, VARI Finance Director 

Kathryn Bishop 

Mark Denhof 

Sandi Dulmes 

Nate Gras 

Rami Ibrahim 

Tess Kittridge 

Angie Lawrence 

Leah Postema 

Susan Raymond 

Cindy Turner 

Human Resources 

Linda Zarzecki, Vice President 

Ryan DeCaire 

Deirdre Griffin 

Eric Miller 

Pamela Murray 

John Shereda 

Erica Siebrasse 

Darlene Walz 


Information Technology 

Bryon Campbell, Ph.D., 

Chief Information Officer 

David Drolett, Manager 

Zack Ramjan, Manager 

Candy Wilkerson, Manager 

Bill Baillod 

Terry Ballard 

Tom Barney 

Phil Bott 

James Clinthorne 

Kim Coan 

Dan DeVries 

Sean Haak 

Kenneth Hoekman 

Matt Hoffman 

Jason Kotecki 

Diana Lewis 

Ben Lewitt 

Deb Marshall 

Randy Mathieu 

Matt McFarlane 

Rob Montroy 

David Mowry 

Bruce Racalla 

Thad Roelofs 

Anthony Watkins 

Innovation and Collaboration 

Jerry Callahan, Ph.D., M.B.A., I&C Officer 

Norma Torres 

Investments Office 

Kathy Vogelsang, 

Chief Investment Officer 

Ted Heilman 

Karla Mysels 

Turner Novak 

Austin Way 

Legal 

Thomas R. Curran, Jr., General Counsel 

Materials Management 

Richard M. Disbrow, C.P.M., Director 

Matt Donahue 

Tracey Farney 

Heather Frazee 

Desaray Fourman 

Justin Harper 

Cheryl Poole 

Shannon Rydel 

Bob Sadowski 

Kyle Sloan 

Kimberly Stringham 

John Waldon 

Tracey Walker 

Security 

Kevin Denhof, CPP, Director 

Shelly Adamczak 

Brian Nix 

Chelsea Sturm 

Ross Vander Klok 

Andriana Vincent 

Sponsored Research 

Jeff Richardson, Director 

Kathy Koehler 

Sara O’Neal 

Heather Wells 

Barbara Wygant 


Van Andel Institute 

Board of Scientific Advisors 

Michael S. Brown, M.D., Chairman 

Richard Axel, M.D. 

Joseph L. Goldstein, M.D. 


Phillip A. Sharp, Ph.D. 

Van Andel Institute Board of Trustees 

David Van Andel, Chairman 

John C. Kennedy 

Mark Meijer 


Board of Trustees 


Tom R. DeMeester, M.D. 

James B. Fahner, M.D. 

Michelle Le Beau, Ph.D. 

George F. Vande Woude, Ph.D. 

Ralph Weichselbaum, M.D. 

Max Wicha, M.D. 


Chief Scientific Officer 

Peter A. Jones, Ph.D., D.Sc. 

Innovation & Collaboration 

Jerry Callahan, Ph.D. 

VP Human Resources 

Linda Zarzecki 

Communications & Marketing 

Beth Hinshaw Hall 

Compliance 

Gwenn Oki, M.P.H. 

Facilities 

Samuel Pinto 

Chief Executive Officer 

David Van Andel 

Chief Operations Officer 

Jana Hall, Ph.D., M.B.A. 

Van Andel Education Institute 

Board of Trustees 


James E. Bultman, Ed.D. 

Donald W. Maine 

Juan R. Olivarez, Ph.D. 

Gordon L. Van Harn, Ph.D. 

Van Andel Education Institute 

Director 

Terra Terrango 

VP & Chief Financial Officer 

Timothy Myers 

General Counsel 

Thomas R. Curran, Jr. 

Development 

Brett Holleman, CFRE, CFRM 

Security 

Kevin Denhof 


The Van Andel Institute and its affiliated organizations (collectively the “Institute”) support and comply with 

applicable laws prohibiting discrimination based on race, color, national origin, religion, gender, age, disability, 

pregnancy, height, weight, marital status, U.S. military veteran status, genetic information, or other personal 

characteristics covered by applicable law. The Institute also makes reasonable accommodations required by 

law. The Institute’s policy in this regard covers all aspects of the employment relationship, including recruiting, 

hiring, training, and promotion, and, if applicable, the student relationship. 

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2018 Scientific Report

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