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Using JAK inhibitors to prevent the effects of hypoxia and inflammation in transplantation

Using JAK inhibitors to prevent the effects of hypoxia and inflammation in transplantation

PhD/Honours project

Inflammation and hypoxia are the main causes of early islet loss, and occur throughout the isolation and transplant procedure. We recently made the finding that inhibitors of JAK1/JAK2, the kinases downstream of many cytokines, not only circumvented cytokine-induced cell death and pro-immunogenic effects (i.e. MHC class I upregulation), but they also protected islets from hypoxia-induced inflammatory responses and cell death. This effect was unexpected, though very potent, and observed in both human and mouse islets under experimental hypoxic conditions. JAK inhibitors could therefore present a therapeutic opportunity to protect islets from damage and loss during islet isolation and transplantation. We will investigate molecular responses to hypoxia, inflammatory stress and JAK inhibitors in islets in vitro, to determine the islet-intrinsic factors that are critical for islet damage and death, and then test if JAK inhibitor treatment can protect transplanted islets in a mouse model of type 1 diabetes. The lab is in the unique position to test new improved protocols for human islet isolation and transplantation, with a clinical islet isolation facility at SVI, and a transplant team at St Vincent’s Hospital Melbourne.

Supervised by:

  • A/Prof Helen Thomas
  • Dr Michaela Waibel
  • Disease Focus:

  • Islet transplantation
  • Research Unit:

  • Islet biology