The UF Diabetes Institute

Last week, we announced the creation of the UF Diabetes Institute. Given the many fundamental contributions of our faculty to this field over the years, the UF Diabetes Institute designation was long overdue. At a time when much attention is appropriately being directed to newly created “preeminence programs” at UF, including programs at UF Health, it is important that we celebrate and invest in faculty who have created academic and clinical programs that are already preeminent.

In forming the UF Diabetes Institute, we celebrate and invest in our longstanding efforts to prevent, diagnose and treat diabetes. Establishing this institute will bring together the extraordinary clinical and research expertise that exists across our campus in all facets of diabetes, improve education and training in diabetes, and provide for future growth in diabetes research. Moreover, working with the Institute of Food and Agricultural Sciences, the Diabetes Institute aims to create more effective prevention initiatives across all 67 counties in Florida. The institute will include nearly 100 faculty members from the colleges of Medicine, Engineering, Pharmacy, Public Health and Health Professions, Nursing and Dentistry as well as IFAS, and is believed to be the only institute of its kind nationally to leverage such intellectual breadth and depth.

Diabetes, which afflicts an estimated 29 million Americans and 1 in 10 Floridians, describes a group of metabolic diseases characterized by high blood glucose levels. Adjusted for age, persons with diabetes have death rates two to four times higher than the rest of the population. Diabetes can affect one or many organ systems. Heart and vascular disease, kidney failure and stroke are the most frequent complications, but diabetes can also lead to eye disease (retinopathy, cataracts, glaucoma), kidney failure, amputation, nerve damage and/or gum disease. One out of every four adult patients admitted to a UF Health hospital last year had a diabetes diagnosis among their clinical issues. The American Diabetes Association estimated that $18.6 billion was spent to provide care for people with diabetes in the state of Florida in 2012.

Type 1 diabetes (T1D), which accounts for about 10 percent of all diabetes, results from the body’s failure to produce enough insulin as a result of a destructive process of the insulin-producing cells. Type 2 diabetes (T2D; about 90% of cases) begins with insulin resistance, in which the body's cells do not respond properly to insulin, thus requiring more insulin. As the disease progresses, the body’s ability to make insulin cannot keep up with the increased demand. Patients with high blood sugar will typically experience frequent urination (polyuria), and become increasingly thirsty (polydipsia) and hungry (polyphagia). Gestational diabetes occurs when pregnant women without a history of diabetes develops high blood glucose levels. Gestational diabetes resolves with childbirth, but such women are at higher risk for developing diabetes later in life.

The origin of the UF Diabetes Institute has its roots in the late 1960s, and the story of how our T1D research program has evolved into one widely considered to be among the top five in the nation is a compelling lesson in how a passion for discovery and clinical innovation leads to new research paradigms and improved patient care nationally.

The story begins with Arlan L. Rosenbloom, M.D., who was recruited to UF from the University of Wisconsin in 1968 as our founding pediatric endocrinologist. Beginning with funds from the March of Dimes Birth Defects Center, and continuing with a grant for the regional diabetes program from Children’s Medical Services, he was able to develop a comprehensive program that included clinics throughout North and Central Florida. During the late 1970s, Dr. Rosenbloom obtained recurring funds from the Florida Legislature to create the Diabetes Research, Education and Training Center at UF, which provided support for pediatric, adult and maternal diabetes programs at UF. Using these various funding sources to leverage an ambitious vision, Dr. Rosenbloom pioneered efforts to define and achieve the optimal management of patients with T1D, emphasizing the importance of a team approach, including nurse educators.

In 1970, Dr. Rosenbloom also began Florida’s Camps for Children and Youth with Diabetes. In addition to a fun-filled normal camping opportunity that children with diabetes might not otherwise have, his philosophy was that these camps would be an extension of the academic pediatric diabetes program encompassing superlative care, education, training and research. This program has grown to be a statewide, year-round effort involving pediatric diabetologists, nurses and other health professionals from other institutions and private practice. Dr. Rosenbloom also initiated a strong and varied clinical research program and showed a commitment to scholarship that inspires faculty to this day. Over the past half-century, he has authored or co-authored almost 400 articles, about 120 of them since becoming professor emeritus in 1999! His accomplishments have been recognized by numerous awards, including the UF Distinguished Achievement Award.

From Dr. Rosenbloom onward, the diabetes story at UF reads like a genealogy tree. He was instrumental in the 1970s in recruiting Janet Silverstein, M.D., (professor in UF’s department of pediatrics and chief of pediatric endocrinology) as well as Noel Maclaren, M.D., who later became chair of the department of pathology. Dr. Maclaren, in turn, brought to UF’s diabetes program a number of investigators: Mark Atkinson, Ph.D., Michael Clare-Salzler, M.D., and Desmond Schatz, M.D., each of whom has become a leader in the field. These faculty members in turn have recruited the next generation of diabetes researchers at UF, from both the T1D and T2D realms. All are committed to improving the lives of those with the disease and preventing the disorder from occurring in those at risk for diabetes. Indeed, they have worked to convince a series of promising young researchers (for example, Clayton Mathews, Ph.D., and Todd Brusko, Ph.D., both now members of UF’s department of pathology, immunology and laboratory medicine) to call UF their new home. In addition, we have expanded our view of diabetes at UF beyond T1D through the recruitment of Kenneth Cusi, M.D., as chief of the division of endocrinology, diabetes and metabolism in the Department of Medicine. Dr. Cusi is widely recognized for his efforts regarding liver function and its relationship to T2D.

Through the years, studies of T1D have been a major area of emphasis for the investigators noted above, as well as others at UF. As a result of the contributions of these faculty members, UF has been recognized internationally as one of the leading centers investigating the natural history, prediction and prevention of this disease. The scope of this program has historically been expansive and path-breaking:

• using autoantibody markers to predict individuals at increased risk of T1D;
• identifying genes associated with genetic susceptibility;
• characterizing the cellular (i.e., T cell, macrophage) immune response in its natural history;
• defining the physiology of the immune response;
• identifying agents suitable for the prevention of T1D in humans; and
• uncovering key aspects of the pathogenesis of T1D in animal models for the disease.

In addition, laboratories at UF have served as “reference or referral” centers for many worldwide standardization programs for T1D. As a result of these long-standing efforts, the diabetes research group has developed and maintained an extremely valuable patient resource. This resource, ongoing clinical trials related to natural history and novel treatments, and ongoing basic science research into immune mechanisms using clinical samples and preclinical animal models, makes the UF Diabetes Institute a unique environment for education, research and translation to patient care.

Over the years, UF made several major institutional commitments that have had a dramatic influence on our diabetes research program. The first of these was an initial investment of $5.5 million in the 1990s to initiate the gene therapy program by recruiting new faculty and establishing a core facility for the viral vectors used in such therapy. This initial investment has yielded significant dividends, including four NIH-funded “program project” grants. These are large awards to study research themes that tie together a number of related and complementary scientific projects. As a result of this success, UF’s T1D research group obtained a $10 million grant from the Juvenile Diabetes Research Foundation to use gene therapy as a means of preventing or reversing T1D, as well as alleviating its complications.

To continue the momentum of this research, the university provided an additional $6.5 million investment to create a Good Manufacturing Practices facility for production of clinical grade vectors for human therapeutic trials, and significant philanthropic support was obtained from Earl Powell to establish the Powell Gene Therapy Center. More recently, an additional multimillion-dollar investment was made to expand the existing vector facility, which now has received NIH funding as a hub for preclinical trials under the leadership of the Powell Center’s director, Barry Byrne, M.D.

Institutional commitments have also been made to improve the lives of those with diabetes. Also beginning in the 1990s, the Diabetes Center of Excellence was formed by Drs. Silverstein and Schatz, a unit dedicated to the integration of patient care, education and research as applied to diabetes. The success of this unit attracted $600,000 per year in recurring annual funding from the state of Florida.

In the mid-2000s, Craig Tisher, M.D., then dean of the College of Medicine, provided $9.7 million in new research support to allow for the recruitment of new faculty members with interest in the immunopathogenesis and prevention of T1D. As was the case with the investment in gene therapy, faculty in the Diabetes Center of Excellence leveraged these funds to obtain many competitive grants and contracts from the NIH, JDRF and the American Diabetes Association. This investment has led to many research awards, notably two awards in 2013 from the JDRF to UF for studies of the pancreas in T1D ($14.3 million and $3.9 million, respectively) and renewal of an NIH Program Project (P01) for years 15 through 20 ($5.5 million). UF’s recent entry into a highly competitive, NIH-funded process to identify the best centers in the U.S. capable of attempting to prevent and/or reverse T1D was funded with the second best score in the nation. Beyond this, UF became one of the first four institutions (along with Harvard, Columbia and UCSF) to receive a major award from the Leona M. and Harry B. Helmsley Charitable Trust for studies seeking to cure T1D ($3.6 million). This is but a partial listing of the benefits of these initial investments by UF leadership into its diabetes programs. Collectively, this work has created new research paradigms and is poised to improve the lives of those with this disease.

More recently, Dr. Mike Good, dean of the College of Medicine, recognized continued investment in our diabetes research program with a multi-year commitment of $6 million for additional faculty recruitment, pilot studies and administrative support, including appointment of the UF Diabetes Institute’s administrative director, Les Jebson, M.H.A.

While UF has long been proud of its efforts toward prevention and immunopathogenesis and prevention of T1D, through leadership provided by Drs. Atkinson, Clare-Salzler and Schatz, important advances have also occurred in the therapeutic translation of research findings. Indeed, in the previous five years, “bench to bedside” translational activities have occurred with six UF T1D-related projects: umbilical cord blood therapy for T1D prevention as well as combination therapies for T1D reversal (Michael Haller, M.D.; Mark Atkinson, Ph.D., and Desmond Schatz, M.D.), two different approaches to therapies for diabetic retinopathy (William Hauswirth, Ph.D.; Ed Scott, Ph.D.), accelerated wound healing (Gloria Chin, M.D.), and the prevention of T1D through newborn nutritional therapy (Michael Clare-Salzler, M.D.).

Many members of the UF Diabetes Institute, including Drs. Mark Atkinson, Todd Brusko, Kenneth Cusi, Michael Clare-Salzler, Desmond Schatz, Michael Haller, Clayton Mathews and David Ostrov (from the College of Medicine), Benjamin Keselowsky and Cherie Stabler (from the College of Engineering) and Patrick Concannon (from the Genetics Institute) are recognized nationally and internationally for their individual contributions to diabetes research and innovation. However, UF’s expertise in the study of diabetes extends throughout the campus, including Michael Perri, Ph.D., and Arch Mainous, Ph.D., (from the College of Public Health and Health Professions), Eric Triplett, Ph.D., (Microbiology and Cell Science), Brent Summerlin (Chemistry), John Driver, Ph.D., (Animal Sciences), Anne Mathews, Ph.D., and Linda Bobroff, Ph.D. (IFAS).

The diabetes effort at UF has been a team effort, in which the whole has been greater than the sum of its parts. While there is insufficient space in this newsletter to detail the important work of each member of the team, it would be incomplete unless I explained that the excitement and growth in diabetes research and patient care over the past two decades at UF has been spearheaded by UF Diabetes Institute Director Mark Atkinson and Institute Co-Director, Desmond Schatz.

Dr. Atkinson is the American Diabetes Association eminent scholar for diabetes research at UF, and has just completed his year as only one of two term professors of the University of Florida Foundation. He is beginning his 30th year of investigation into the field of T1D and has authored over 375 publications, many with lasting impact in the field. Indeed, Thomson Scientific (an organization that tracks scientific citations of researchers) noted that Dr. Atkinson was the fifth-most-cited authority of over 65,000 investigators in the world in all categories of diabetes, both type 1 and type 2. In June 2014, Enterscape noted him as the No. 2 ranked individual, at a global level, for influence in the field of diabetes. For these efforts, and for his service to the field, Dr. Atkinson has been the recipient of many scientific and humanitarian awards, including four notable awards from JDRF and the highly prestigious Eli Lilly Award for Outstanding Scientific Achievement from the ADA. In 2009, he received the ADA’s “Cure Award.” Dr. Atkinson has been the recipient of numerous research grants and contracts. His program currently receives approximately $6 million in annual extramural funding. Beyond his research accomplishments, Dr. Atkinson is known by many for spending large amounts of time with people who either have or who care for those with T1D — addressing their questions and sharing his passion and desire to see a cure for the disease. He serves on the International Advisory Board for Life for a Child, and recently assumed the role of president for Insulin for Life USA; both organizations specifically dedicated to getting insulin to those globally where access to this life-saving drug is limited.

Dr. Schatz is a professor and associate chairman of pediatrics, medical director of the Diabetes Institute and director of the UF Clinical Research Center. He has been involved in T1D research since the mid-’80s, has published over 260 manuscripts (the majority related to the prediction, natural history, genetics, immunopathogenesis and prevention of the disease), and treats children and adolescents with T1D. He is the principal investigator on several JDRF and NIH awards. He is PI on JDRF-funded studies aimed at reversing T1D using autologous stem cells (cord blood) and is currently PI of the UF Clinical Center in the NIH-funded TrialNet. He serves as co-PI on a Program Project Grant focused on the immunopathogenesis of T1D, and also serves as co-PI for the NIH-funded international newborn genetic screening (TEDDY) program in North Central Florida. He has served in numerous leadership and scientific capacities for the American Diabetes Association and is the president-elect of the ADA.

Under the leadership of Drs. Atkinson and Schatz, the UF Diabetes Institute will be guided by a number of core values and priorities, including a mechanistic understanding of diabetes in the context of a translational focus, a commitment to recruit new investigators to the field of diabetes research and to train young researchers, collaboration with other scientists nationally and internationally studying diabetes, and partnership with industry.

The new institute’s momentum is underlined by recent funding. Four UF researchers recently received five separate grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH. Each of the grants was funded through the Human Islet Research Network, recently launched by the NIDDK, to study the function of pancreatic islet beta cells, which are the body’s insulin-producing cells. When beta cells die, insulin levels drop, triggering diabetes. In T1D, an autoimmune response causes the body to destroy these cells.

• Cherie Stabler, Ph.D., a recent hire in the department of biomedical engineering, received a $4.9 million collaborative grant to engineer a microchip that would serve to house islets that produce beta cells. Her team hopes to use the microchips to improve the current amount of islets available to transplant into patients with diabetes, screen pharmaceuticals for patients with diabetes and/or create beta cells from stem cells.
• Martha Campbell-Thompson, D.V.M., Ph.D.,a professor of pathology, immunology and laboratory medicine, received a $1.6 million grant in collaboration with UF’s Clayton Mathews, Ph.D., (see below) and Ivan Gerling, Ph.D., at the University of Tennessee. These investigators will use a microscope fitted with lasers to cut out the tissue containing only the islets. The researchers will then isolate RNA from the islets that still have insulin-producing beta cells and compare it with RNA taken from islets lacking beta cells. This research draws on pancreas tissue from organ donors who lived with diabetes, through the Network for Pancreatic Organ Donors with Diabetes, or nPOD, a biorepository formed at UF in 2006. Islet beta cells are difficult to study in living patients, so most studies rely upon research samples from nPOD.
• Campbell-Thompson’s grant dovetails with a grant to Clayton Mathews, Ph.D., also a professor of pathology, immunology and laboratory medicine. Mathews is investigating the genetics of beta cell destruction in T1D. His $3.1 million grant questions whether a specific copy of a gene increases a person’s risk of developing diabetes. His team will examine genes they suspect contribute to the disease. Mathews was also awarded a $2.6 million grant as a co-principal investigator with researchers from Battelle Pacific Northwest Laboratories and Harvard University to discover early breakdown in the regulation of gene expression, leading to stress and death of beta cells. Their grant will also identify early biomarkers of beta cell death and potential targets for therapy.
• While Mathews’ grant will try to determine why beta cells fail, Des Schatz, M.D., and his colleagues will be using a $1.4 million grant to explore novel methods to detect the death of beta cells in blood samples. This work is being done in collaboration with Drs. Yuval Dor (Hebrew University) and Jorge Ferrer (Imperial College, London).

Thus, serendipitously, the UF Diabetes institute has seen an extraordinary launch. What does the future hold? According to Dr. Atkinson, “One day, a means for preventing as well as curing diabetes will be found and with full sincerity, when that occurs, I firmly believe the efforts of UF staff and faculty toward that goal will be seen by many as being key to its discovery. Working together, my hope is that the UF Diabetes Institute will make that important event occur soon.”

Forward Together,

David S. Guzick, M.D., Ph.D. Senior Vice President for Health Affairs, UF President, UF Health