By Morgan Sherburne
More than 30 years ago, Mark Atkinson, PhD ’88, was given three research questions that he would spend his career trying to solve. What is the cause of Type 1 diabetes? Who may develop the disease — and why? Can we find a cure?
And in the years since, Atkinson, now director of the University of Florida Diabetes Institute, and Desmond Schatz, MD, the institute’s medical director for Type 1 diabetes, have resolutely maintained a strong team of researchers to chip away at those questions and to translate their findings to the care of patients.
While other institutions often find it challenging to sustain a research endeavor that has the kind of influence and staying power UF’s diabetes program has had over the decades, UF now looks to its third generation of physicians and scientists to make their own mark on the global effort to prevent and cure diabetes.
“The diabetes team at UF is quite unique in academia,” explained Atkinson, who was recruited in part through inspiration provided by its founder, Dr. Arlan Rosenbloom. “Some of my colleagues and I have worked together at UF for more than three decades. People come here and catch the vision to impact diabetes, and that vision forms the glue that holds us together. As a result, they don’t leave … and for us, that is a good thing.”
Schatz agrees, saying the program’s legacy is its talent for attracting new team members who continue to provide insight into the mechanisms of diabetes and ways to impact care for those with it. He points to Michael Haller, MD, a 2000 graduate of the UF College of Medicine who began working under Schatz’s tutelage as a UF undergraduate. Haller, who has led first-of-its-kind clinical trials studying the use of cord blood, as well as combination drug therapies to prevent or reverse Type 1 diabetes, was recently named chief of pediatric endocrinology at the UF College of Medicine.
“Mike (Haller) started working with us when he was 18, and now he’s leading the division,” Schatz said. “He is the next generation, and now there are folks who are following after him.”
The lineage of UF’s diabetes program dates back to 1968 with Rosenbloom, who brought Janet Silverstein, MD, now a professor in the department of pediatrics, and Noel Maclaren, MD, on board. Atkinson and Schatz, associate chair of pediatrics in the UF College of Medicine who recently began his term as president of the American Diabetes Association, began researching Type 1 diabetes in the early ’80s. With Michael Clare-Salzler, MD, current chair of the UF College of Medicine’s department of pathology, immunology and laboratory medicine, they represent UF’s second wave of diabetes scientists and clinicians.
Their protégés, including Haller and colleagues like Clayton Mathews, PhD, the Sebastian Family professor for diabetes research, and Clive Wasserfall, MS ’98, make up the third wave, and already they have helped attract the latest vanguard of researchers who appear to be following traditions by pushing the boundaries of diabetes research and care. Highlighted here are just a few of what should be UF’s latest generation of promising researchers in diabetes.
Todd Brusko, PhD
Todd Brusko, PhD ’06, can easily say he’s studied diabetes at UF for more than 15 years — even though the researcher is only 37.
Brusko, who leads a laboratory in the department of pathology, immunology and laboratory medicine, started working as an undergraduate in a Type 1 diabetes genetics lab at UF. After completing a doctoral degree in the UF College of Medicine’s Interdisciplinary Program in Biomedical Sciences, Brusko studied as a post-doctoral researcher at the University of California – San Francisco before returning to UF in 2010.
“I had just an incredible graduate experience under the mentorship of Mark Atkinson,” Brusko said. “I developed a fascination with the immune system and the way it’s controlled.”
Through his research, Brusko is trying to understand how a defect in immune regulation leads to Type 1 diabetes. During Type 1 diabetes, a person’s immune cells, specifically T cells, begin attacking beta cells in the pancreas. Beta cells produce insulin, which is needed for the control of blood sugar levels.
Brusko thinks some of the genes related to Type 1 diabetes cause T cells to attack beta cells.
“We’re trying to correct a primary autoimmune defect in patients,” Brusko said. “Our research hopes to not only cure the disease but prevent it from occurring.”
Jing Chen, MD, PhD
Jing Chen, MD, PhD, started her study of Type 1 diabetes in her home country of China, when she first was faced with an overwhelming number
of patients with diabetes.
“After I graduated from medical school, I did my residency in a university hospital,” Chen said. “I saw so many diabetic patients but knew there was no cure. That’s when I started my career in diabetes.”
After completing postdoctoral work in the United States, Chen began working with Mathews, also a professor in the UF department of pathology, immunology and laboratory medicine, but then at the University of Pittsburgh.
Chen and Mathews have shown how dysfunction in mitochondria, organelles within cells that produce energy, may contribute to the development of Type 1 diabetes.
“We think this type of dysfunction contributes to the development of Type 1 diabetes,” Chen said. “Our group was the first to study this type of dysfunction in human Type 1 diabetes, and we’ve found some very exciting results.”
The group hopes to discover ways therapies can target T cell mitochondrial function that will prevent the immune system from attacking beta cells.
Laura Jacobsen, MD
When Laura Jacobsen, MD ’12, returned to UF after a residency at the University of North Carolina in Chapel Hill, she wasted no time becoming involved in a project or three. Or four. Or five.
A new pediatric endocrinology fellow at UF, Jacobsen is working with Schatz and Haller.
Jacobsen’s first project uses data from nPOD, a repository of donated pancreas tissue established by UF’s Atkinson and hosted by the Juvenile Diabetes Research Foundation. The nPOD network provides pancreatic tissue for researchers all over the world to study.
Typically, researchers use the repository to study what happens in the organ of someone who has diabetes. But Jacobsen is working with Schatz to study how the person who donated the pancreas lived — and died.
“It’s very stressful to have a chronic illness,” Jacobsen said. “Diabetes, if well-managed, is not a life-threatening illness, but it is incredibly hard to live with.”
When pancreas tissue is donated to nPOD, medical records and history are included, providing information about what caused that person’s death. A donor may have died from complications with diabetes such as diabetic ketoacidosis —
a condition in which a person doesn’t have enough insulin to convert glucose into energy and begins breaking down fat, releasing ketones. It can send a person with diabetes into a coma, or cause death. Researchers also learn about factors that could have contributed to a person’s heart attack, kidney disease or stroke.
The donor’s medical history doesn’t just note physical complications from disease. For example, a history of drug or alcohol abuse could indicate to researchers that some patients require help in managing their stressful disease. A donor’s death by suicide could show physicians a need for emotional support and mental health.
“What this could tell us is whether we need better screening tools and better support for patients,” Jacobsen said.
Jacobsen is also assisting Haller with clinical trials that examine if some medications can slow the rate of beta cell decline. With Janet Silverstein, MD, Jacobsen is studying a way to use a portable eye scanner to test for retinopathy in children with Type 1 diabetes.
Kenneth Cusi, MD
UF has long been recognized internationally as a leading center for Type 1 diabetes research — but Type 2 diabetes and diabetes in adults is reaching a fever pitch across the United States. Leaders at UF Health took note and expanded the institution’s focus on the disease.
Enter Kenneth Cusi, MD, chief of the division of endocrinology, diabetes and metabolism in the UF College of Medicine’s department of medicine. Cusi was recruited to UF in 2011 to help grow the adult medical diabetes program. And he has.
The year before Cusi arrived, the endocrine team consulted on just 360 patients hospitalized for complications of diabetes. In 2015-2016, that number has grown to more than 6,000. At the Malcom Randall Veterans Administration Medical Center, where Cusi was chief of endocrinology from 2013-2015, the number of visits from patients with diabetes tripled to 7,000 visits per year. At UF Health Endocrinology – Medical Specialties – Medical Plaza’s outpatient clinic, physicians had 12,000 patient visits in just the last year.
“My primary aim was to develop a comprehensive state-of-the-art endocrine and diabetes program and to make three parts of such a program flourish: to develop patient care, to develop the next generation of doctors and to create a cutting-edge research program in Type 2 diabetes and obesity,” Cusi said.
The division of endocrinology has grown from a faculty of four to 15. The endocrinology fellowship has likewise grown from two positions to five, and according to the numbers, the country really needs this kind of education.
“There are about 2,500 active clinical endocrinologists in the United States to take care of about 30 million people with diabetes, and millions of patients with endocrine disorders,” Cusi said.
Cusi developed a program called the Diabetes Care Task Force, a multidisciplinary team whose goal is to make UF Health a premier institution for diabetes care. The program oversees care for adult patients with Type 2 and Type 1 diabetes — about 30 percent of adult patients seen at UF Health have Type 1 diabetes.
“A lot of the patient’s anxiety gets taken out of the way because they see a team working for them,” Cusi said.
Along with developing UF Health’s capacity to care for patients and training future endocrinologists, Cusi continues to delve into the factors that contribute to the complications associated with diabetes. He’s an expert in nonalcoholic fatty liver disease, or NAFLD, a condition that affects about two-thirds of patients with Type 2 diabetes. These patients are also at the highest risk of the more severe form of liver inflammation known as nonalcoholic steatohepatitis, or NASH, which often leads to end-stage liver disease.
“A lot of the patient’s anxiety gets taken out of the way because they see a team working for them.” – Kenneth Cusi, MD
“In the past 10 years, we have discovered that obesity and Type 2 diabetes cause excessive fat accumulation in the liver,” Cusi said. “If this goes undiagnosed for a long time, it can lead to progressive liver damage and end-stage liver disease. NASH is now the second-leading cause of liver transplantation in the United States.”
Undiagnosed, the disease can also lead to a type of cancer called hepatocellular carcinoma, as well as cardiovascular disease.
“We are developing new technologies to diagnose NAFLD at an earlier stage,” Cusi said. “Our group is also the first to provide proof-of-concept to show that this kind of liver disease can be treated with medication.”
Working together for a diabetes-free world
At UF, the work of diabetes scientists and clinicians is interwoven, which Atkinson says is a must.
“Our objective in establishing the UF Diabetes Institute is to create an interdisciplinary team to study genetics, nutrition, lifestyle and socioeconomics and how they relate to this disease — that’s the future of finding a cure not just for Type 1 diabetes, but all diabetes,” Atkinson said. “And as this next generation of scientists enters, our goal is to expand our scope to include Type 2 diabetes, obesity and nutrition.
“The state of diabetes research, care and training has never been better at the UF College of Medicine,” he continued. “What has kept us together for all these years is our mission. Everything we do, whether in the lab or in the clinic, is designed to help improve the life of someone with diabetes.”
The University of Florida’s history of diabetes excellence dates back to 1968, when Dr. Arlan Rosenbloom joined UF as its first pediatric endocrinologist. Through the following decades, national leaders in Type 1 diabetes research and care like Janet Silverstein, MD; Mark Atkinson, PhD ’88; and Desmond Schatz, MD; built a world-renowned program and assembled an interdisciplinary team focused on tackling one of the most intractable diseases of our time.
In 2014, the university officially pulled all of that research together with the launch of the UF Diabetes Institute, with Atkinson as director and Schatz as medical director for Type 1 diabetes. The institute brings together nearly 100 faculty members from the colleges of Medicine, Engineering, Public Health and Health Professions, Nursing and Liberal Arts and Sciences as well as the Institute of Food and Agricultural Sciences and UF Health Jacksonville in the fight to cure both Type 1 and Type 2 diabetes.
From clinicians to researchers to social workers to teachers, nearly every department that can contribute to diabetes research is involved. The interdisciplinary approach has turned UF into a hub for diabetes work and has attracted a cadre of talented researchers and grants.