2022 Annual Report

Scientists redefine obesity with discovery of
two distinct subtypes
A team led by VAI scientist Dr. J. Andrew Pospisilik
has identified two distinct types of obesity with
physiological and molecular differences that may have
lifelong consequences for health, disease and response
to medication. The findings, published in the journal
Nature Metabolism, offer a more nuanced understanding
of obesity than current definitions and may one day
inform more precise ways to diagnose and treat obesity
and associated metabolic disorders. The study also
revealed new details about the role of epigenetics and
chance in health and provides insights into the link
between insulin and obesity. 2
Creation of new tool represents a paradigm
shift in epigenetics research of model systems
for human disease
Epigenetics plays a role in virtually every aspect of
health and disease, but studying exactly how and why
epigenetic changes affect us has been a challenge due
to a lack of appropriate tools and techniques. Now, VAI
scientists and their collaborators have developed a
powerful new tool that will help us better understand
how epigenetics maintains health and, when things go
wrong, promotes diseases such as cancer. The research
was led by VAI’s Dr. Peter W. Laird and Dr. Hui Shen
and will facilitate groundbreaking research around
the world. 3
New technique helps scientists run circles
around cancer
Rampant inflammation has long been linked to cancer,
but exactly how it pushes healthy cells to transform
into malignant ones has remained a mystery. Now,
VAI scientists have found one culprit behind this
connection: oxidative stress, a process that disrupts the
genetic code by damaging DNA. The findings, published
in Science Advances, provide crucial new insights into
the roles of inflammation and oxidative stress in certain
cancers and offers new opportunities for potential
prevention strategies. This work was made possible
using a new technique called circle damage sequencing
developed by the lab of VAI’s Dr. Gerd Pfeifer. In 2021,
Pfeifer’s lab also used circle damage sequencing to
determine that the mutations that give rise to
melanoma result from a chemical conversion in
DNA damaged by sunlight — not just a DNA
copying error as previously believed. 4
Dr. Yvonne Fondufe-Mittendorf joins VAI
Epigenetics expert Dr. Yvonne Fondufe-Mittendorf
joined VAI’s growing faculty as a professor in January
2022, a move that expanded the Institute’s research into
the relationship between environmental exposures and
cancer. Fondufe-Mittendorf studies the relationship
between environmental factors, such as arsenic in
drinking water, and cancer risk. Her research has
revealed how low-dose arsenic exposure transforms
healthy cells into malignant ones — revelations that have
significant public health implications.
Funding Acknowledgements
Research reported in this publication was supported by:
1
Van Andel Institute and the National Institute on Aging of the National Institutes
of Health under award no. R01AG066764 (Laird and Shen). Approximately 50% of the
funding for this study came from federal sources; approximately 50% came from nonfederal
sources.
2
Van Andel Institute; Max Planck Gesellschaft; the European Union’s Horizon 2020
Research and Innovation Program under Marie Skłodowska-Curie grant agreement
no. 675610; the Novo Nordisk Foundation and the European Foundation for the Study of
Diabetes; the Danish Council for Independent Research; the National Human Genome
Research Institute of the National Institutes of Health under award no. R21HG011964
(Pospisilik); and the NIH Common Fund, through the Office of the NIH Director (OD),
and the National Human Genome Research Institute of the National Institutes of Health
under award no. R01HG012444 (Pospisilik and Nadeau). Approximately 5% ($50,000) of
funding for this study is from federal sources; approximately 95% ($950,000) is from
non-U.S. governmental sources.
3
Van Andel Institute; Children’s Hospital of Philadelphia; and the National Cancer
Institute of the National Institutes of Health under award nos. R01CA157918,
R01CA212374 and R01CA234125 (Laird). Shen is supported by the National Cancer
Institute of the National Institutes of Health under award no. R37CA230748. Jones is
supported by the National Cancer Institute of the National Institutes of Health under
award no. R35CA209859.
4
Research reported in this publication was supported by Van Andel Institute and
the National Cancer Institute of the National Institutes of Health under award no.
CA228089 (Pfeifer).
The content is solely the responsibility of the authors and does not necessarily represent
the official views of the National Institutes of Health or other funders.
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