Prestigious Awards Bolster Diabetes Center ResearchThree recent awards totaling $22 million will support the

Diabetes Center’s efforts to expand our understanding of

obesity and autoimmune disease mechanisms and devise

new treatment strategies for patients.

Local Foundation Creates Diabetes and Obesity Research Program

A $5 million gift from The Joseph & Vera Long Foundation will establish the

Joseph & Vera Long Foundation Diabetes and Obesity Research Program

and support innovative obesity- and diabetes-related investigations across

UCSF’s campuses. A portion of the gift also will create the Joseph & Vera Long

Foundation Endowed Professorship in Diabetes and Obesity, which will be held

by a leading researcher in the Diabetes Center.

Left to right: Christian Vaisse, MD, PhD, and Matthias Hebrok, PhD, director of the Diabetes Center, confer with graduate student researcher Thomas Hennings.

WINTER 2015/2016

News from the

Diabetes Center at UCSF

The Joseph & Vera Long Foundation’s transformational gift to our diabetes and obesity research program will significantly accelerate our efforts to address one of the greatest public health challenges of our generation. Christian Vaisse, MD, PhD Vera M. Long Endowed Chair in Diabetes Research

(continued inside)

From the Director

MilestonesFifteen years ago, UCSF founded a comprehensive Diabetes Center, uniting researchers,

clinicians, and educators as an integrated team focused on improving the quality of life

for people living with diabetes.

We have come a long way since then. Through collaborative partnerships and the generous support of donors like

you, the Diabetes Center at UCSF has become one of the world’s most highly respected programs for diabetes

research and care. UCSF is now part of a small, elite group of institutions nationwide that are designated by the

National Institutes of Health as both a Diabetes Research Center and a Nutrition and Obesity Research Center.

These honors are a testament to our track record of devising innovative strategies to prevent, treat, and ultimately

cure both type 1 and type 2 diabetes.

As we celebrate the progress we’ve made over the last 15 years, we thank you for your steadfast belief in our work.

None of our successes would be possible without the loyalty of our friends in the community.

With best wishes for a happy holiday season,

Matthias Hebrok, PhDDirector, Diabetes Center at UCSF Hurlbut-Johnson Distinguished Professor in Diabetes Research

UCSF is now part of a small, elite group of institutions nationwide that are designated by the NIH as both a Diabetes Research Center and a Nutrition and Obesity Research Center. Matthias Hebrok, PhD

2 News from the Diabetes Center at UCSF

Prestigious Awards(continued from front page)

Affecting more than 79 million adults in the US alone,

obesity is a growing epidemic and a major risk factor for

type 2 diabetes.

“With this generous gift, the Long Foundation makes a bold

statement about the importance of obesity research to all

patients and families who are affected by diabetes,” said

Matthias Hebrok, PhD, director of the Diabetes Center. “The

discoveries we make about the biological mysteries of type

2 diabetes and obesity also will help us to better understand

type 1 diabetes, potentially leading to improved treatments

and cures for both forms of the disease.”

The Joseph & Vera Long Foundation is a private, family

foundation that provides financial support to qualified,

not-for-profit organizations involved with health care,

education, and conservation in the communities of Northern

California and Hawaii. The foundation is a longtime partner

of the Diabetes Center at UCSF, having previously funded a

number of research and educational priorities, including the

Vera M. Long Endowed Chair in Diabetes Research, held

by Christian Vaisse, MD, PhD; the Vera M. Long Foundation

Gene Therapy Suite at the UCSF Islet and Cellular

Transplantation Facility; and the Vera M. Long Outstanding

Diabetes Scientist Post-Doctoral Fellowship.

NIH Taps UCSF as Home for New Research Center

The National Institutes of Health (NIH) has awarded

UCSF $7 million to launch the UCSF Nutrition and Obesity

Research Center (NORC) – one of only 12 such centers

in the nation.

Led by senior Diabetes Center faculty member Christian

Vaisse, MD, PhD, the center comprises 44 UCSF

researchers who study obesity and metabolism from

multiple, complementary avenues. The goal of the team is

to define the underlying mechanisms of the disease and

contribute to prevention and treatment measures for

obesity and its complications.

NORC funding will support core facilities that research

teams can access for expertise, training, and equipment

for state-of-the-art obesity and nutrition-related

experiments. The funding also will support research

grants to encourage innovative pilot studies that

challenge conventional wisdom on obesity, diabetes,

and nutrition.

Sean N. Parker Autoimmune Research Laboratory Launched

The Parker Foundation, founded by Silicon Valley entre-

preneur and philanthropist Sean Parker, has contributed

$10 million to launch the Sean N. Parker Autoimmune

Research Laboratory within the Diabetes Center.

The lab will be headed by Jeff Bluestone, PhD, the

A.W. and Mary Margaret Clausen Distinguished

Professor in Metabolism and Endocrinology. It will

focus on increasing our understanding of autoimmunity

and accelerating the development of new treatments for

type 1 diabetes and other autoimmune diseases such

as multiple sclerosis and rheumatoid arthritis.

“This gift is a testament to Dr. Bluestone’s leadership in

the immunology field, as well as the Diabetes Center’s

instrumental role in shaping diabetes research and care,”

says Dr. Hebrok. “We are very grateful for the Parker

Foundation’s support, which will further strengthen the

Diabetes Center’s outstanding research program in

autoimmune diseases.”

Jeff Bluestone, PhD (right), working in his lab with postdoctoral fellows Armando Villalta, PhD, and Melanie Matheu, PhD

News from the Diabetes Center at UCSF 3

New-Onset Type 1 Diabetes

Clinical Trials Yield Promising ResultsNewly diagnosed type 1 diabetes patients often still have a functional remnant of

insulin-producing beta cells. Preserving these cells delivers tremendous benefits to

the patient because improved blood sugar control within two years of diagnosis can

help protect against long-term complications – even if the patient eventually requires

supplemental insulin or has difficulty maintaining blood sugar control at a later date.

The Diabetes Center leads and participates in numerous clinical trials aimed at

protecting existing beta cells in recently diagnosed patients. Three particularly

promising studies are described on the next page.

The Diabetes Center’s clinical trials program is led by Stephen Gitelman, MD, the Mary B. Olney, MD/KAK Distinguished Professor in Pediatric Diabetes and Clinical Research.

4 News from the Diabetes Center at UCSF

ALEFACEPT TRIAL: In this multi-center trial, our team assessed

whether alefacept – a drug formerly used to treat psoriatic arthritis

– could slow or halt the destruction of beta cells in newly diagnosed

type 1 diabetes patients. As reported in the Journal of Clinical

Investigation in July 2015, the trial showed highly encouraging

results. Specifically, participants who were given alefacept

benefited from sustained preservation of beta cells even two years

after entering the study and 15 months after stopping treatment.

Alefacept works by targeting effector T cells, the immune cells that

cause the destructive autoimmune response in type 1 diabetes.

ATG + GCSF TRIAL: In a small initial phase 2 trial, our team

worked with colleagues at the University of Florida and the

University of Colorado to determine if a combination of two drugs

– anti-thymocyte globulin (ATG) and granulocyte-colony stimulating

factor (GCSF) – could preserve beta cells in patients within two

years of disease onset. As reported in the Journal of Clinical

Investigation in January 2015, the trial’s results were positive,

with treated subjects showing stabilization in beta cell function,

compared to steady loss in the placebo group. The combination

of ATG and GCSF appears to reset the balance of effector T cells

to Tregs. Tregs, or regulatory T cells, are rarer immune cells that

protect beta cells against immune attack. A larger phase 2 trial is

now underway for subjects within 100 days of diagnosis.

TREG TRIAL: The Diabetes Center’s Jeff Bluestone, PhD, has

developed a way to purify and grow Tregs in our cell manufacturing

facility. Dr. Bluestone’s research has previously revealed that Tregs

can reverse diabetes in a mouse model. Over the past several

years, our clinical trials team, led by Stephen Gitelman, MD, has

conducted a phase 1 study with these cells, demonstrating that

they are safe, well-tolerated, and may halt beta cell destruction in

humans. The team is now launching a phase 2 study to validate the

findings in a larger adolescent patient population. Team members

are extremely excited about this endeavor, as they believe it may

eventually enable us to move beyond drugs – and their associated

toxicities – to develop cell-based strategies for controlling the

autoimmune response in humans.

How the Treg Trial Works

Our team isolates and purifies each trial participant’s unique sub-population of protective T cells, called Tregs, from the participant’s blood sample. The team then expands the Tregs approximately 1,000-fold in UCSF’s cell culture facility and, after two weeks, reinfuses the cells back into the patient. Preliminary results indicate this strategy is well- tolerated and safe, and it may be effective in protecting beta cells from autoimmune attack in new-onset diabetes.

To view the list of current type 1 clinical trials actively enrolling participants, please visit diabetes.ucsf.edu/clinical_trials.

For questions, please contact clinicalresearch@diabetes.ucsf.edu or call 844-T1D-UCSF.

News from the Diabetes Center at UCSF 5

ANDERSON LAB: In a paper published in the Journal of

Experimental Medicine, the Anderson team reported its groundbreaking

discovery of a major switch that turns on the AIRE gene. Produced

in the thymus, the AIRE gene helps teach infection-fighting T cells to

distinguish the body’s own proteins from those of foreign invaders,

thereby preventing autoimmunity.

BHUSHAN LAB: Working with the Hebrok team, the Bhushan lab

provided new insights into the mechanisms that influence how beta cells

mature after birth. Reported in the Journal of Clinical Investigation, the

team’s findings suggest that beta cell dysfunction in diabetes may be

due in part to epigenetic factors – external or environmental processes

that affect how genes are expressed. Unlike DNA sequence mutations,

epigenetic changes appear to be reversible, thereby providing a

potential new target for therapies.

The Year in Basic Research Research findings our team

has contributed to the field in

2015 include the following:

2015

6 News from the Diabetes Center at UCSF

Wilsey Family Fellowship

Educating the Next Generation of Leaders in Diabetes Research and CareEarlier this year, Michael Wilsey (center)

met with the 2015-2016 recipients of the

Wilsey Family Fellowship – Sahar Hindi, MD;

Eunice Chuang, MD; and Kelly Wentworth,

MD – and Michael German, MD, director

of the Integrated Fellowship Training

Program in Diabetes, Endocrinology, and

Metabolism (DEM) at UCSF. (Not pictured:

Wilsey Family Fellow Diana Alba, MD.)

HEBROK LAB: As detailed in The Embo

Journal, the Hebrok lab described a new

technique for transforming human embryonic

stem cells into insulin-producing beta cells

in the laboratory. The team’s results were of

such high quality that its lab-made cells are

now equivalent in many ways to normally

functioning human beta cells.

In recognition of his team’s innovative research

in pancreatic and beta cell development, beta

cell differentiation, and islet cell regeneration,

Dr. Hebrok was selected as the recipient

of the 2015 JDRF Gerold & Kayla Grodsky

Basic Research Scientist Award. This honor

is presented annually to a researcher who has

made outstanding scientific contributions to

type 1 diabetes research.

KAJIMURA LAB: As reported in Nature

Medicine, the Kajimura lab was the first to

isolate energy-burning “beige” fat, which is

known to be able to convert unhealthy

white fat into healthy brown fat, from adult

humans.The team also found new genetic

markers of this beige fat. The discovery is

an important advance in the search for new

medications to fight obesity.

KOLIWAD LAB: In a high-impact review

published in the Annual Review of Physiology,

the Koliwad team shed new light on the

way the brain senses the presence and

absence of nutrients. This emerging area of

science, which includes key cutting-edge

work from the Koliwad lab, is uniting the

fields of lipid metabolism, inflammation, and

neurophysiology to uncover how the brain links

food consumption to metabolic function, body

weight, and the control of blood glucose.

Established by a generous gift from

Mr. Wilsey and his wife, Bobbie,

the Wilsey Family Fellowship supports

the clinical research of talented trainees

in the DEM program.

News from the Diabetes Center at UCSF 7

For more information about the Diabetes Center at UCSF, please contact Jessica Jencek at 415-476-3215 or Jessica.Jencek@ucsf.edu.Follow the Diabetes Center online at diabetes.ucsf.edu and on Twitter @UCSFDC.

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News from the Diabetes Center at UCSF is produced by the UCSF Office of University Development and Alumni Relations

Managing Editor/Writer: Jeanette Anders | Editor: Mark Goldstein

Photography: Steve Babuljak, Susan Merrell | Design: Laura Myers Design

© 2015 The Regents of the University of California

15th Anniversary

2015 Diabetes Center SymposiumThe UCSF community and members

of the public gathered on October 30,

2015, for the Diabetes Center at

UCSF 15th Anniversary Symposium.

Attendees learned about the latest

research being conducted by top

investigators in the fields of both

type 1 and type 2 diabetes.