Richard E. Weitzman Outstanding Early Career Investigator Award
Nima Sharifi, MD
Nima Sharifi, MD, is the Kendrick Family Endowed Chair for Prostate Cancer Research at the Cleveland Clinic Foundation. He has quickly become a leader in castration-resistant prostate cancer (CRPC) research, using innovative strategies to boldly rewrite the pathways of androgen synthesis and to unravel the endocrinology of this deadly hormone-dependent cancer. His laboratory demonstrated that 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) is a key enzyme for the conversion of adrenal-derived precursors to androgens in prostate cancer cells and that the pathway from dehydroepiandrosterone to dihydrotestosterone primarily proceeds via androstenedione and 5α-androstanedione rather than testosterone. He then explained why some CRPC cells have high 3βHSD activity, due to a common germline allele that blocks ubiquitination and markedly prolongs the protein half-life without altering activity. He also showed that human CRPC metastases select for this allele, which portends poor prognosis. Most recently, his laboratory demonstrated that abiraterone, a CYP17A1 inhibitor, undergoes metabolism to active metabolites and that the 3-keto-Δ4-homolog is a potent inhibitor not only of CYP17A1 but also 3βHSD, 5α-reductase, and the androgen receptor.
His distinguishing features include his bold approach to challenge dogma, his talent for designing the difficult but critically important experiments to directly address questions, his fearlessness when incorporating foreign techniques and venturing outside his comfort zone to solve these problems, and his insistence on taking his work from the bedside to the bench and back to the bedside.
His work has been recognized with the 2014 American Association for Cancer Research Award for Outstanding Achievement in Cancer Research, an American Cancer Society Research Scholar Award, election to the American Society of Clinical Investigation, and three R01 grants. He is also a dedicated and skilled teacher, mentor, and clinical oncologist. He is a uniquely qualified physician-scientist and an ideal candidate for the Richard E. Weitzman Outstanding Early Career Investigator Award.
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