DUARTE, Calif.–(BUSINESS WIRE)–#CityofHope—Bart Roep,
Ph.D., City of Hope’s Chan Soon-Shiong Shapiro Distinguished Chair in
Diabetes, professor/founding chair of the Department
of Diabetes Immunology and director of The
Wanek Family Project for Type 1 Diabetes, continues to break
new ground in revealing the relationship between type 1 diabetes and the
body’s natural defenses.
Roep was invited to speak about his research at the American Diabetes
Association’s (ADA’s) 79th Scientific Sessions, held June
7-11, 2019, in San Francisco. Roep and several City of Hope colleagues
highlighted research successes and presented recent findings.
Nearly 15,000 leading physicians, scientists and health-care
professionals gathered at the conference to unveil leading-edge
research, treatment recommendations and advances toward a cure for
diabetes, which is associated with significant increases in inflammation
and debilitating vascular complications that can lead to blindness and
heart and kidney failure.
The root of type 1 diabetes
Roep spoke on a featured symposium titled “The
Complicit Beta Cell in Type 1 Diabetes.” His talk, “Antigenic
Peptides Are Generated Through Beta-Cell Translational Errors,” centers
on an important revelation that came out of Roep’s laboratory in 2017:
Type 1 diabetes (T1D) results from a mistake in the insulin-producing
beta cells of the pancreas, not an error of the immune system, the
previously accepted explanation for how the disease begins.
According to Roep’s findings, beta cells in T1D seem to produce abnormal
proteins from the insulin gene that provoke immune responses. This is
because of a “wrong read” of the insulin gene — a mechanism similar to
what happens in some tumors. In addition to shedding light upon why some
cancer patients develop T1D after successful immunotherapy, this
discovery suggests new directions for treatments for T1D. Roep and his
collaborators have built upon those investigations to explore a
potential diabetes vaccine.
Exploring epigenetics
Rama Natarajan,
Ph.D., City of Hope’s National Business Products Industry Professor in
Diabetes Research and professor/chair of the Department of Diabetes
Complications & Metabolism, gave a talk titled “Epigenetics
of Inflammation and Diabetic Vascular Complications” as part of a
featured symposium. Discussing her research into diabetes and
epigenetics, or the changes that are made to genes by external or
environmental factors, she underlined data collected by her lab that
shows many inflammatory and fibrotic genes associated with diabetic
complications are regulated by epigenetic mechanisms, and highlighted a
clinical trial that elucidated the importance of strict glycemic control
to prevent progression of diabetes-related complications.
Natarajan reviewed epigenetics data that her lab has generated with
samples obtained from subjects enrolled in the Diabetes Control and
Complications Trial (DCCT), which ran from 1983 to 1993, and from the
current, long-term follow-up Epidemiology of Diabetes Interventions and
Complications (EDIC) study, which also demonstrated the phenomenon of
metabolic memory that results in long-term malfunction of genes and
sustained complications even after patients with diabetes bring their
blood sugar under control.
“Building on that knowledge, we have used epigenomic approaches with
samples from DCCT/EDIC type 1 diabetes patients to demonstrate a role
for epigenetic mechanisms in this intriguing phenomenon of metabolic
memory,” Natarajan said. “It shows that DNA is not your destiny: Despite
being born with ‘good’ genes, your lifestyle can change things for the
worse and vice versa via epigenetics.”
Another important part of Natarajan’s research is focused on the role of
noncoding RNAs that form another epigenetic layer. These different
epigenetic layers can cross talk and amplify pathological genes in
diabetes.
“In the future, precision medicine with genetic, epigenetic and clinical
information will help in more effective diagnosis and treatment of
diabetes and its complications,” Natarajan said. “Furthermore,
epigenetic variations are reversible and therefore provide an additional
opportunity for therapeutic intervention.”
At the ADA conference, two postdoctoral scholars from Natarajan’s lab,
Maryam Abdollahi, Ph.D., and Ragadeepthi Tunduguru, Ph.D., also
presented their work with noncoding RNA. The three women worked together
on both projects, along with Mitsuo Kato, Ph.D., an associate research
professor in the Natarajan lab, and additional collaborators.
Beta cell diversity
Sangeeta
Dhawan, Ph.D., City of Hope assistant professor of translational
research and cellular therapeutics, delivered a talk on “Beta cell
heterogeneity: a neuronal story” in a session entitled “Will
the Real Beta Cell Please Stand Up?” Her research focuses on beta
cells, the cells in the pancreas that produce insulin. A deficit of
functioning beta cells is behind the symptoms of both type 1 and type 2
diabetes.
Dhawan’s work adds to a growing body of evidence indicating that not all
beta cells are the same. Her presentation concerned two novel
subpopulations of beta cells that exhibit molecular features similar to
neurons (cells of the brain and nervous system). She discussed the
changes that occur in these distinct sub-types during beta cell growth
and in diabetes, and presented the epigenetic mechanisms that drive
these differences in beta cells.
‘Good’ fat
Qiong
“Annabel” Wang, Ph.D., City of Hope assistant professor of molecular
and cellular endocrinology, gave a presentation titled “315-OR
– Two brown adipocyte subpopulations with distinct thermogenic activity
coexist and undergo dynamic interconversions upon changes in
environmental temperature.” In this research, she investigates brown
fat, a type of darker-colored and richly veined fat that plays a role in
warming up the body. Brown fat actually seems to have beneficial effects
upon obesity and the insulin resistance seen in diabetes.
The previous understanding was that brown fat cells are more or less
similar. Wang presented a discovery from her lab: A subtype of brown fat
cells with distinct qualities, including low thermogenic activity — that
is, they generate less heat.
Furthermore, she described how the two groups of brown fat cells convert
from one to the other. Under normal circumstances, highly thermogenic
brown fat cells are recruited to turn into the newly described subtype
that have lower thermogenic activity. When ambient temperatures become
cold, the opposite happens, with the newly described brown fat cells
changing into brown fat cells that create more warmth.
About City of Hope
City of Hope is an independent biomedical research and treatment center
for cancer, diabetes and other life-threatening diseases. Founded in
1913, City of Hope is a leader in bone
marrow transplantation and immunotherapy such as CAR
T cell therapy. City of Hope’s translational research and
personalized treatment protocols advance care throughout the world.
Human synthetic insulin and numerous
breakthrough cancer drugs are based on technology developed at the
institution. A National Cancer Institute-designated comprehensive cancer
center and a founding member of the National Comprehensive Cancer
Network, City of Hope is ranked one of America’s “Best Hospitals” in
cancer by U.S. News & World Report. Its main campus is
located near Los Angeles, with additional
locations throughout Southern California. For more information
about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
Contacts
Letisia Marquez
626-476-7593
lemarquez@coh.org