Michael Ohh

Dr. Michael Ohh received his PhD from the University of British Columbia under the supervision of Dr. Fumio Takei and advisor Dr. Connie Eaves at the Terry Fox Laboratory, BC Cancer Agency. He then completed a Medical Research Council and National Cancer Institute of Canada postdoctoral fellowship in the laboratory of Dr. William G. Kaelin Jr. at the Dana-Farber Cancer Institute and Harvard Medical School where he made foundational discoveries of the metazoan oxygen-sensing pathway that contributed to Dr. Kaelin’s shared 2019 Nobel Prize in physiology or medicine.

Since establishing his laboratory at the University of Toronto, Dr. Ohh has continued his ground-breaking research including the unified theory underlying the pathogenesis of von Hippel-Lindau disease and other pseudohypoxic syndromes and the ‘dark state’ of canonical RAS GTPase cycle, supporting the revelation of indirect inactivation of RAS, the most commonly mutated oncoprotein driving human cancers that has remained until then undruggable.

Dr. Ohh is a recipient of Bernard and Francine Dorval Prize from the Canadian Cancer Society, Premier’s Research Excellence Award, and Canada Research Chair in Molecular Oncology.  

Research Synopsis

Role of tumour suppressors and oncoproteins in cancer biology

Cancer is a disease characterized by uncontrolled cell growth that can spread to other parts of the body and the second leading cause of death globally. Our research mission is to elucidate the molecular mechanisms governing the function of two major cancer-associated proteins called von Hippel-Lindau (VHL) tumour suppressor protein and Rat Sarcoma (RAS) oncoprotein with the supposition that lessons learned would provide fundamental understanding of normal and cancer cell biology and lay the foundation for the development of rational anti-cancer therapies.

Our multidisciplinary research approach focuses on molecular biology and protein biochemistry, providing an excellent training ground for graduate students and postdoctoral fellows who wish to pursue a career in academia. Our research principles emphasize the rigorous pursuit of truth and the mandate of being right over first. Past members have garnered competitive scholarships, recruited to prestigious institutions such as Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Dana-Farber Cancer Institute, Genentech, Stanford, Yale, M.I.T., and Harvard, and have established their own research programs at world-class centres around the world.

Selected Publications

Erythrocytosis-inducing PHD2 mutations implicate biological role for N-terminal prolyl-hydroxylation in HIF1α oxygen-dependent degradation domain. Taber CC, He W, Gasmi-Seabrook GMC, Hubert M, Ferens FG, Ikura M, Lee JE, Ohh M. Elife. 2025 Oct 20; 14:RP107121.

Time-resolved NMR detection of prolyl-hydroxylation in intrinsically disordered region of HIF-1α. He W, Gasmi-Seabrook GMC, Ikura M, Lee JE, Ohh M. Proc Natl Acad Sci USA. 2024 Sep 10;121(37):e2408104121. 

Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation. Kano Y, Gebregiworgis T, Marshall CB, Radulovich N, Poon BPK, St-Germain J, Cook JD, Valencia-Sama I, Grant BMM, Herrera SG, Miao J, Raught B, Irwin MS, Lee JE, Yeh JJ, Zhang ZY, Tsao MS, Ikura M, Ohh M. Nature Communications. 2019 Jan 15;10(1):224.

HIF2α-pVHL complex reveals broad genotype-phenotype correlations in HIF2α-driven disease. Tarade D, Robinson CM, Lee JE, Ohh M. Nature Communications. 2018 Aug 22;9(1):3359.

Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis. Bunda S, Burrell K, Heir P, Zeng L, Alamsahebpour A, Kano Y, Raught B, Zhang ZY, Zadeh G, Ohh M. Nature Communications. 2015 Nov 30;6:8859.

Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation. Bunda S, Heir P, Srikumar T, Cook JD, Burrell K, Kano Y, Lee JE, Zadeh G, Raught B, Ohh M. Proc Natl Acad Sci USA. 2014 Sep 9;111(36):E3785-94.

Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Niemeyer CM, Kang M, Shin DH, Furlan I, Erlacher M, Bunin NJ, Bunda S, Finklestein JZ, Mehta P, Schmid I, Kropshofer G, Corbacioglu S, Lang PJ, Klein C, Schlegel PG, Heinzmann A, Stary J, van den Heuvel-Eibrink MM, Hasle H, Locatelli F, Sakai D, Archambeault S, Chen L, Russell RC, Sybingco SS, Ohh M, Braun BS, Flotho C, Loh ML. Nature Genetics. 2010 Sep;42(9):794-800.

Regulation of endocytosis via the oxygen-sensing pathway. Wang Y, Roche O, Yan M, Finak G, Evans AJ, Metcalf JL, Hast BE, Hanna SC, Wondergem B, Furge KA, Irwin MS, Kim WY, Teh BT, Grinstein S, Park M, Marsden PA, Ohh M. Nature Medicine. 2009 Mar;15(3):319-24.

HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Kirscher MW, Asara JM, Lane WS, Kaelin WG Jr. Science. 2001 Apr 20;292(5516):464-8.

Ubiquitination of HIF requires direct binding to the beta-domain of the von Hippel-Lindau protein. Ohh M, Park CW, Ivan M, Hoffman MA, Kim T-Y, Huang LE, Pavletich N, Chau V, Kaelin WG Jr. Nature Cell Biology. 2000 Jul;2(7):423-7.

The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov A, Louis DN, Gavin BJ, Kley N, Kaelin WG Jr, Iliopoulos O. Molecular Cell. 1998 June;1(7):959-68.