Partial Antagonists of IRE1 RNASE – ‘pairs’ – to treat type 1 diabetes

Contact PI: Feroz Papa, MD, PhD, University of California, San Francisco (U01 DK123609)

Dustin Maly, PhD, Washington University, Investigator
Start Date: September 20, 2019
End Date: July 21, 2023


Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by hyperglycemia due to progressive immune-mediated destruction of pancreatic beta cells. Recent work from our laboratories has shown that hyperactivation of the unfolded protein response (UPR) to ER stress in the immune-targeted beta cells may be a critical early event in the development of T1D. We have developed novel pharmacological reagents called `PAIR’s that allow us to manipulate components of the UPR. Importantly, first generation versions of small molecules—called KIRAs— delivered to NOD mice can efficaciously prevent and even reverse diabetes in this T1D model. Thus, in this collaborative grant we will capitalize on the complementary expertise of the investigators to optimize these PAIR lead molecules for potency and selectivity, conduct proof of concept studies using human islets, and perform key enabling steps needed to advance these candidates further into the clinic for treating human patients with T1D.

Meet the Grant Team 



Feroz Papa, MD, PhD

University of California, San Francisco


Dustin Maly, PhD

University of Washington









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