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Repurposing JAK1/JAK2 inhibitors to treat type 1 diabetes

Repurposing JAK1/JAK2 inhibitors to treat type 1 diabetes

PhD project

Our goal is to prevent the immune-mediated destruction of insulin-producing pancreatic beta cells that leads to type 1 diabetes. The JAK-STAT signalling pathway is critical for immune-mediated pancreatic beta cell destruction. We have exciting data showing that inhibitors of JAK1/JAK2 prevent diabetes and also reverse newly diagnosed diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. These results provide a compelling rationale to apply JAK1/JAK2 inhibitors, some of which are approved for human use, to the prevention and treatment of type 1 diabetes in humans. The goal of this project is to investigate the use of JAK inhibitors for the treatment of type 1 diabetes.

We propose to take considerable steps towards achieving our goal to use JAK inhibitors to prevent type 1 diabetes in humans. One of these is to determine which of the many JAK inhibitor drugs in development is the best to use in type 1 diabetes. Another step is to identify the best way to test that JAK inhibitors are affecting type 1 diabetes pathogenesis in patients. We will then conduct a clinical research study using intermediate markers to determine whether JAK inhibitors are likely to be effective in patients with type 1 diabetes. Finally we will use a discovery approach to identify molecules that are affected by inhibition of JAK/STAT signalling. This will give us a better understanding of the mechanisms by which JAK inhibitors work. Understanding the target of the JAK inhibitors in diabetes prevention may lead to identification or development of drugs with more specific action, thus refining future trials for cytokine inhibition in type 1 diabetes.

Supervised by:

  • A/Prof Helen Thomas
  • Prof Tom Kay
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Islet biology