UF Diabetes Institute researchers to study genetic variations and autoimmune response in type 1 diabetes with 5-year NIH grant

Story at a glance:

  • In February, UF Diabetes Institute researchers received a $1.25 million grant from the NIH to study how specific genetic variation impacts the autoimmune disease  type 1 diabetes.
  • Researchers hope to identify therapeutic targets on white blood cells capable of blocking inflammatory signals to stop the destruction of insulin-producing beta cells.
  • The goal is to stop the autoimmune process that is attacking and destroying pancreatic beta cells and prevent the disease process in those at risk or preserve beta cell function when possible.

University of Florida Diabetes Institute researchers received a 5-year R01 grant to understand how genetic variations impact the autoimmune response in individuals with type 1 diabetes.

White blood cells circulate the body and protect the host from pathogens such as bacteria and viruses. In patients who develop type 1 diabetes, a small fraction of white blood cells activate in an uncontrolled manner and destroy insulin-producing beta cells.

Beta cell destruction ultimately causes patients to develop type 1 diabetes, as they are unable to produce enough insulin to control their blood sugar levels.

“There is currently no cure for type 1 diabetes,”  said Todd Brusko, Ph.D., the principle investigator for the study. “Patients must manually control their blood sugar levels with shots and, too often, that process results in long-term side effects and complications from poor blood glucose control.”

The grant goal is to better understand the immune system’s regulation process. By understanding the cells and pathways that stop immune responses, researchers hope to reverse the disease process in patients who develop type 1 diabetes.

This award will address a critical and unmet need in the field, which is to understand how specific gene variants impact immune function,” said Shannon Wallet, Ph.D., an associate professor in the UF College of Dentistry’s department of oral biology.

The key to the research is a population of CD4 T-cells, called regulatory T-cells. Researchers hope to bolster these cells and unlock their potential in treating autoimmune diseases.

“We know that genes control risk for developing autoimmune diseases like type 1 diabetes,” Brusko said. “What is not well understood is how these small genetic differences between individuals change the immune response and lead to disease.”

With this funding from the  National Institute of Diabetes and Digestive and Kidney Diseases, Brusko and his team will focus on understanding the immune system’s “checkpoints” that activate regulatory T-cells.

“Eventually, this path of investigation will allow researchers to create antibodies or therapeutic agents to block the signals driving inflammation and beta cell destruction,” said Brusko, an assistant professor in the University of Florida College of Medicine’s Department of Pathology, Immunology and Laboratory Medicine and a member of the UF Diabetes Institute. “Essentially, it gives us a biological target important in the disease process.”

By isolating highly potent regulatory T-cells and harnessing their ability to block immune responses, researchers hope to reverse the uncontrolled destruction of beta cells in type 1 diabetes patients.

Correcting this defect could not only prevent the disease in those at risk, but it could also protect new beta cells in patients with type 1 diabetes who have received replacement therapies involving stem cells or transplanted beta cells.

“This work may directly result in new therapeutic agents and new cellular therapies for the treatment of Type 1 diabetes,” Brusko said.

By Nate Phillips, UF Diabetes Institute