CMiST_draft_JUN 7

parkerdesign

Center for Microbiome Sciences

and Therapeutics


We are home to an enormous microbial ecosystem

containing more than 100 trillion bacteria, a number

equal to our own human cells. More astonishing than

the number of bacteria is the sheer amount of genetic

diversity these bacteria contribute to our physiology.

It is estimated that for every one of our genes, there

are approximately 145 microbial genes. This roughly

equals 3.3 million bacterial genes in the intestine to

the 23,000 in the human genome (Qin, 2010).

Collectively, these bacteria are referred to as the

microbiota and they perform essential functions in

the maintenance of our health. However, shifts in the

composition, distribution and/or function of the microbiota

have been implicated in diseases of the GI

tract such as inflammatory bowel disease (IBD) and

colorectal cancer (CRC).


It has become increasingly evident that the state of

our gut also influences our entire physiology, playing

important roles in systemic diseases such as autism,

hematological cancers and multiple sclerosis.

To understand this complex community, it will take

investigators from distinct scientific backgrounds

working together towards a common goal. If that

goal is to cure disease then cooperation and collaboration

between clinicians and scientists must be a

priority.

With PhD leadership that is part of UW Medicine

Division of Gastroenterology, and a physical presence

in the UW Health Sciences buildings, CMiST is

poised to serve as a point of connection and communication

between clinicians and scientists. As

the UW’s designated microbiome research center,

we are in an advantageous position to make significant

advances in microbiome research, specifically

the microbiome of the gut, that will ultimately help

millions of people.


Our Vision

To be the foremost leader in

microbiome research throughout the

Pacific Northwest region known for

our thoughtful collaborations, our

unique approach to experimental design

and our dedication to educating

the community about the importance of

the microbiome in maintaining a healthy

lifestyle.


Leadership

William DePaolo, PhD

Director

In 2004, Will received his PhD in

Immunology & Microbial Pathogenesis

from the Feinberg School

of Medicine of Northwestern University.

Will then completed his

postdoctoral training at the University

of Chicago where he investigated

the molecular pathogenesis

of Yersinia pestis, the

bacterium that causes bubonic

plague, while concurrently developing

projects investigating immune-modulation within the

intestine.

In 2011, Will joined the faculty at University of Southern California

as an Assistant Professor in the Department of Molecular

Microbiology and Immunology. Will combines his interdisciplinary

training to investigate the contribution of our 100

trillion gut bacteria (or microbiome) to inflammatory diseases

and to develop strategies aimed at manipulating this vast

community. Will’s current research extends across scientific

disciplines and clinical diseases such as obesity, colon cancer,

inflammatory bowel disease and enteric pathogens.

With Will at its helm, CMiST will serve as a beacon for investigators,

clinicians and patients interested in the human

microbiome, and will offer a number of Innovation Services,

facilitate collaboration and exploration through workshops

and seminar series, and work alongside clinicians to develop

and test microbiome-derived therapeutics.


Staff

Amy Parker

Program Manager

Parker is a design strategist and

identity system designer. Having

followed the wrong path in school, (she graduated in 1999

with a BS in Biology from Bates College in Lewiston, ME with

ideas of medical school), she is self-taught. Her lack of traditional

training has challenged her to be resourceful and inventive

in her work. She designs and builds brands based on

her instinct, intuition and diligent research. For CMiST, she

acts as creative director and director of brand strategy, while

also wearing various designer’s hats. In addition to designing

all print, web materials and occasionally presentation materials,

Parker created the visual identity for CMiST and Vivo Art.

We are committed to undestanding the

dynamic interactions between the

microbiome and our own human cells,

to advancing development of

microbiome-based biotherapeutics

to treat or prevent disease.


We have engaged a

world class team

of clinicians, scientists,

educators and artists that

span biomedical and

basic science departments

as well as the arts.


Schools & Colleges

• College of Engineering

• School of Art + Art History + Design

• School of Medicine

• School of Nursing

• School of Public Health

• Rensselaer Polytechnic Institute, Troy, NY

Departments & Divisions

• Arts

(Resselaer Polytechnic Institute, Troy, NY)

• Behavioral Nursing

• Comparative History of Ideas

• Comparative Medicine

• Environmental Health &

Occupational Health Sciences

• Epidemiology

• Global Health

• Human Centered Design & Engineering

• Immunology

• Medicine, Allergy and Infectious Disease

• Medicine, Gastroenterology

• Medicine, Metabolism,

Endocrinology & Nutrition

• Medicine, Pediatrics

• Microbiology

• Pharmacy

• Photomedia


Members & Affliated Members

Anne Stevens, MD, PhD

Seattle Children’s Hospital, Rheumatology

Amy Willis, PhD

UW School of Public Health, Biostatistics

Christiane Hampe, PhD

UW Medicine, Metabolism, Endocrinology & Nutrition

David Beck, PhD

UW College of Engineering, Chemical Engineering

David Suskind, MD

Seattle Children’s Hospital, Gastroenterology

Eric Strachan, PhD

UW School of Medicine, Psychiatry & Behavioral Sciences

Jeffery McClean, PhD

UW School of Dentistry / Periodontics

John Inadomi, MD

UW Medicine, Gastroenterology

Julia Yue Cui, PhD

UW School of Public Health, Environmental & Occupational

Health Sciences

Kathy High, MA

Rensselaer Polytechnic Institute, Arts

Laura den Hartigh, PhD

UW Medicine, Metabolism, Endocrinology & Nutrition


Lisa Strate, MD, MPD

UW Medicine, Gastroenterology

Margaret Heitkemper, FAAN, PhD, RN

UW School of Nursing, Behavioral Nursing and

Health Informatics

Philip Thurtle, PhD

UW, Comparative History of Ideas

Scott Lee, MD

UW Medicine, Gastroenterology

William DePaolo, PhD

UW Medicine, Gastroenterology

William Grady, MD

UW Medicine, Gastroenterology

Neelendu Dey, MD

Fred Hutch Cancer Research Center

Patricia Pavlinac, PhD, MD

UW School of Public Health, Global Health

Piper Treuting, DVM, MS

UW School of Medicine, Comparative Medicine

Stacey Meeker, PhD

UW School of Medicine, Comparative Medicine

Tyler Fox, PhD

UW School of Art + Art History + Design, Human Centered

Design & Engineering


Will DePaolo, PhD and Margaret Heitkemper, FAAN, PhD, RN


Funded

Projects

Project 1

Interrogating the microbiome and

immunity in recurrence of ileal disease

post resection

Project 2

Determine if there are correlations between

changes in the microbiome of IBD

patients and their calprotectin levels

HIV-exposed microbiome impacts the

severity of co-infection


Our tissue sample pipeline

Mucosal associated

bacteria

Bacterial culture

BSL2 room: anaerobic chamber

BSL2 room: MALDI-TOFF BSL2 room: anaerobic chamber

Sample chip can

accommodate

up to 96 unique

samples

Sample collection

(UWGI IBD clinic)

Tissue culture

Sterile cell culture lab: BSC hoods

X

Intestinal tissue

biopsy samples

Intestinal organoids,

aka “mini guts”

Treat organoids

IBD microbiome

biorepository

Laser microdissection

Imaging room:

laser capture microscope

Next gen sequencing

Industry

partnerships


Key Equipment

The Shel Lab Bactron anaerobic

systems have airtight

construction of stainless steel

and rigid Plexiglas for unobstructed

vision and integrity.

Chamber atmosphere circulates

through a condensate

controller then through a catalyst,

which removes any trace amounts of oxygen. High relative humidity

is maintained while condensate moisture is removed without the unnecessary

desiccants, which can dehydrate media and samples. Each unit

contains an integral vacuum pump to provide rapid evacuation of air from

the air lock module for replacement by an inert gas mixture.

The Bruker MALDI Biotyper CA System has been

granted USA FDA clearance under Section 510(k) for

the identification of Gram negative and Gram positive

bacteria, anaerobic bacteria and yeast cultured from

human specimens. The MALDI Biotyper CA System is a

qualitative in vitro diagnostic device indicated for use in

conjunction with other clinical and laboratory findings

to aid the diagnosis of bacterial and yeast infections.

The Laser Microdissection microscope (LMD,

also known as Laser Capture Microdissection

or LCM) enables users to isolate specific single

cells or entire areas of tissue. Powered by

a unique laser design and dynamic software,

Leica LMD systems allow users to easily isolate

regions of Interest (ROI) from entire areas of

tissue down to single cells or even subcellular

structures such as chromosomes.


Project 1

Interrogating the microbiome & immunity in recurrence of

ileal disease post resection

Scott Lee, MD, UWGI

William DePaolo, PhD, UW CMiST

This study aims to further evaluate and define immunological,

metabolic or inflammatory signatures that predispose

patients with Crohn’s disease to post-surgical disease

recurrence as compared to those patients who do

not have significant post-surgical recurrence.

Our goal is to create a hypothesis of how metabolomics

influence and can predict recurrence of Crohn’s post-surgically.

This will lead to more focused and refined studies

to better define this question.

Dr. Scott Lee is an associate professor of medicine

with expertise in inflammatory bowel disease

(Crohn’s disease and ulcerative colitis). His research

is focused on inflammatory bowel diseases

(IBD) including – new therapies for IBD, improving

outcomes in the treatment and long term

management of IBD, evaluation of non-invasive

biomarkers to assess disease activity in IBD patients

and the effects of the microbiome on IBD.


Are there correlations between changes in the microbiome

of IBD patients & their calprotectin levels?

Precise sample selection from each

tissue biopsy using the LCM (Lasercapture

Microdissection Microscope)

Interrogating the microbiome in recurrence

of ileal disease post resection.


We believe that

successful therapeutic

interventions will require

a holistic approach that

takes into account the

molecular pathophysiology

of IBD, specific clinical

parameters and

both immune and

nutritional status.


Scott Lee, MD, UWGI

William DePaolo, PhD, UW CMiST

Project 2

Are there correlations between changes in the microbiome

of IBD patients & their calprotectin levels?

This study aims to investigate the methodology behind

the Calprotectin assay and study specific metabolites

and bacterial composition sf patient fecal samples.


We believe that the

fundamental understanding

of the forces that shape

host-associated microbial

communities and mediate

host-bacterial interactions

is essential for the rational

design of microbiome

therapeutics.


Patricia Pavlinac, PhD

Do changes in the microbiome caused by infection or

antibiotic use alter the expression of genes in the enteric

pathogen leading to an increate in virulence?

Patricia Pavlinac, PhD MS, is an epidemiologist

and co-director of the

Healthy Growth & Development Core of

the Global Center for Integrated Health of

Women, Adolescents, & Children (Global

WACh). Dr. Pavlinac’s research aims

to identify interventions to halt morbidity

and mortality attributed to enteric and

diarrheal diseases. Her other research

interests include pediatric tuberculosis,

particularly the diagnosis of tuberculosis

in pediatric populations.


HIV-exposed microbiome impacts the

severity of co-infection

Patricia Pavlinac, PhD, UW Global WACh

William DePaolo, PhD, UW CMiST

This project seeks to address an important gap in our understanding

of enteric infections that occur in an intestinal

environment with a low bacterial diversity. It proposes a conceptually

innovative hypothesis that the chronic viral infection

itself does not drive Enteropathogenic Escherichia coli

(EPEC) virulence, but rather the reduced gut microbial diversity

caused by the infection. Importantly, this project will

evaluate whether restoration of diversity via fecal microbiota

transplants can be used a treatment strategy.

To answer these questions an integrated, interdisciplinary

approach in mice, humans and bacteria using genomics,

microbiology, and immunology will be used. If successful,

these findings may re-define how we evaluate and treat at

enteric disease not just in HIV but any disease associated

with a reduced microbial diversity, and may provide a biological

framework to develop microbiota-based therapies.


Project initiatives

in diet and nutrition

Graduate student, Denise Chac and


Dietary interventions in

Non-Alcoholic Fatty Liver

Disease (NAFLD) and IBD

NAFLD is a condition in which significant levels of fat builds up

in the cells of the liver leading to a wide spectrum of liver diseases

such as cirrhosis and steatosis (infiltration of liver cells with fat).

In the United States almost 10% of all children and 17% of 15-19

year old children have NAFLD. The need for improved diagnosis

and treatment of NAFLD in children is highlighted by the multiple

complications these children are at high risk of developing, including

atherosclerosis and other cardiovascular complications.

Current research is focused on dissociating the effects of a number

of specialized and popular diets from the effects caused by the

microbiome. We are also beginning exciting collaborations with

clinicians at UWMC and Seattle Children’s we are investigating

the impact of specific diets on children with IBD or NAFLD.

Effect of diet on infectious

disease & vaccination

Poor diets and living conditions are thought to contribute to the low

efficacy rate of oral vaccines in sub-Saharan Africa. In Africa 2.9

million children under the age of five will die from malnutrition

each year and for those that survive nutritional deficiency takes a

toll on their immune system. It is likely that prolonged malnutrition

will also significantly alter the microbiome.

Current research is focused on investigating how different diets impact

not just the host, but the microbiome and the pathogen and the

effects on oral vaccinations.


Bioart is a contemporary art form that adapts

scientific methods and biotechnology

to explore living systems as artistic subjects.

-Yetisen et al. Cell Press 2015


Introducing:

The rapid advancement in scientific technologies and innovations

could easily seem like fiction to the casual observer.

It seems that each day gives us new examples in which

a future could be imagined where we have the capabilities

to radically transform human life in a laboratory. Embodying

these concepts, and pushing the boundaries of science

are central themes present in a recently growing field of art

called Bioart, art works created using scientific processes. In

contrast, a new type of medicine is being embraced by the

medical field, which uses music, dance, and painting in the

rehab and care of patients.

Despite these successful examples of art and science merging

together, the relationship between biomedical research

and art hasn’t been quite as successful. Biomedical-art relationships

tend to ask dynamic and existential questions, such

as ‘what constitutes life’, ‘what is a human being’ and ‘who

are we.’ While interesting, these science-based art projects

do not often include research for the sake of science.

In addition to using bioart as a means to communicate scientific

research to the public, Vivo Art aims to use art to advance

science. Working alongside bioartists allows us to

think even further outside-of-the-box, freeing our minds to be

able to create new hypothesis-based questions, make new

discoveries, or help answer questions in our research that

have been otherwise unsolvable using traditional scientific

processes.

www.cmistuw.org/artists | #VivoArt


Vivo Art

“Scientists sometimes

aren’t so good at

making science

accessible to other

people, but to be able

to convey what you do

and why it matters is vital.

Kathy’s images can tell a

story better than any

dense academic paper.”

-CMiST director, William DePaolo, PhD

Jake Siegel of UW Medicine’s The Huddle,

Vivo Art and current CMiST artist-in-residence Kathy High


Current artists-

Kathy High

Professor of Video and New Media

Department of Arts

Rensselaer Polytechnic Institute, Troy, NY

As part of CMiST Art+Science, world-renowned bio-artist Kathy

High will be doing a recurring artist residency in DePaolo Lab.

Kathy is an artist, but also a person who suffers from inflammatory

bowel disease (IBD). Her passion for trying to understand

this complex disease is part of her art. Kathy has been commissioned

to do an art exhibition in the fall of 2017 with a focus

on IBD and the microbiome. Kathy has shown her work across

the US, as well as Australia, Germany, Poland, Spain, Ireland

and the UK, and is a Guggenheim fellowship recipient.


in-residence

Tyler Fox

Lecturer

Human Centered Design & Engineering

University of Washington, Seattle, WA

Tyler is an artist, researcher, technologist, and educator. His

work focuses on the ways in which nonhuman relations shape

our experience of, and relationship to, the surrounding world.

His teaching fosters interdisciplinary research by nourishing

student-centered projects that incorporate critical theory into

practice-based research. He will be joining the lab at the end

of this month.


UW Medicine | Division of Gastroenterology

1959 NE Pacific Street ,Health Sciences Building, K wing, Suite K443 | Seattle, WA 98195

www.cmistuw.org | Twitter @cmist_uw | #microbiomematters

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