Feroz R. Papa, M.D., Ph.D., is a Professor of Medicine and a physician-scientist at the University of California-San Francisco (UCSF). Dr. Papa completed his medical and graduate school training (in biochemistry and molecular biology on the role of deubiquitinating enzymes in intracellular protein…
more turnover) at the University of Chicago, then did post-graduate clinical training in internal medicine and endocrinology at the University of California, San Francisco (UCSF). Following this, he did a postdoctoral fellowship in biochemistry at UCSF studying the activation mechanism of the endoplasmic reticulum stress sensor IRE1, the master regulator of the unfolded protein response (UPR). During this period he made the seminal discovery that the endoribonuclease domain of yeast IRE1 can be allosterically controlled using kinase inhibitors and kinase catalytic activity completely bypassed in this multi-domain kinase. Following this, Dr. Papa joined the faculty of UCSF, with his lab based at the Mission Bay campus in the multi-disciplinary California Institute for Quantitative Biosciences (QB3). His laboratory has made key fundamental discoveries showing that: (1) mammalian IRE1 controls entry into cell death by endonucleolytically degrading mRNAs localizing to the ER membrane and precursors to microRNAs, in what he has labeled a ‘Terminal UPR’, (2) linked ER stress signaling to sterile inflammation and diabetes, (3) developed small molecule screens, obtained hits, and are advancing lead small molecule kinase inhibitory compounds that can extract either adaptive or destructive outputs from the adjoining RNAse domain of human IRE1, and (4) specifically developed a class of IRE1 inhibitors called KIRAs (for kinase-inhibitory-RNase attenuators) that exploit a therapeutic window to treat myriad ER stress-related diseases that result in premature cell loss (such as diabetes and retinal degeneration). His ultimate goal is to understand the molecular componentry of how cells enter into the terminal UPR, leading to cell degenerative diseases such as diabetes mellitus and neurodegenerative conditions, and to modify these disease states by developing novel therapeutics to ultimately treat human patients. Dr. Papa is the recipient of several national awards and grants, from both federal sources—including the National Institutes of Health Director’s New Innovator Award—and private foundations, including the Juvenile Diabetes Research Foundation, the Burroughs Wellcome Foundation, and the Harrington Discovery Institute.
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