||Hypoxia is a characteristic of most solid cancers, which is associated with resistance towards radiation and chemotherapy. As tumors grow, they can sense the oxygen tension and reprogram critical pathways that are important for cancer cell survival and therapy resistance. One of examples is through upregulation of hypoxia inducible factorα (HIFα) and activation of HIF signaling downstream pathways. My lab is mainly interested in studying the oxygen-sensing pathway and how they contribute to the development of tumors as well as therapeutic resistance. One of the central players in this pathway is prolyl hydroxylase (EglN1, 2 and 3), a family of iron- and 2-oxoglutarate-depedent dioxygenases. EglNs can hydroxylate HIFα on critical proline residues, which will trigger von Hippel-Lindau (VHL)-associated E3 ligase complex binding and lead to HIFα degradation. One of research directions in the lab is trying to identify novel EglN prolyl hydroxylase substrates and examine their role in cancer. The other direction is to focus on examining the VHL and its bona-fide substrates in kidney cancer. Overall, my lab currently studies hypoxia, prolyl hydroxylase and VHL signaling in cancer, especially breast and renal cell carcinomas.
Keywords: Hypoxia, oxygen sensing, breast cancer, kidney cancer, VHL, EglN.-Dr. Qing Zhang