Molecular Mechanisms and Translational Investigation of Advanced Prostate Cancer
Cleveland Clinic, Cleveland, OH
A postdoctoral fellowship position supported by the National Institutes of Health and the Prostate Cancer Foundation are available in the laboratory of Dr. Nima Sharifi at the Cleveland Clinic.
Our laboratory is focused on metabolic and molecular mechanisms of androgen synthesis and androgen receptor (AR) gain-of-function that lead to resistance to hormonal therapy. Specific areas include:
1) Metabolic and genetic changes required for hormone therapy resistance in prostate cancer and tumor progression
2) Clinical validation in patients and clinical trials utilizing innovative approaches
3) Animal models of advanced prostate cancer for translational and therapeutic studies
4) Identifying targets for the development of new pharmacologic therapies
We discovered the first example of a gain-of-function in a steroid-synthesizing enzyme that enables prostate cancer resistance to hormonal therapy (Chang, et al. Cell. 2013 154(5):1074-1084) and that we have shown in a predictive biomarker of poor outcomes after hormonal therapy (Hearn, et al. Lancet Oncol. 2016 17(10):1435-44; Hearn, et al. JAMA Oncol. 2018 Apr 1;4(4):558-562). We are current evaluating this biomarker in a clinical trial and are pursuing similar mechanisms and developing new treatment modalities based on these discoveries.
We recently also discovered that abiraterone works by conversion to a more active steroidal metabolite (Li, et al. Nature. 2015 523(7560):347-51), that metabolism is pharmacologically modifiable to optimize therapy (Li, et al. Nature. 2016 533(7604):547-51), that this is a class effect of steroidal androgen synthesis inhibitors (Alyamani, et al. Cell Chemical Biology. 2017 24, 1-8, July 20) and genetic determination of metabolite generation (Alyamani, et al. J Clin Invest. 2018 Aug 1;128(8):3333-3340).
The position will provide a unique and multidisciplinary exposure to tumor metabolism, molecular oncology, drug development and clinical trials. Further details are available at the following link: https://www.lerner.ccf.org/cancerbio/sharifi/#lab
Candidates should hold a doctoral degree with a background in molecular biology, chemistry, metabolism or cancer biology. Candidates must have proficiency in verbal and written English.
Candidates with an interest in the position should send their CV and contact information for 3 references to:
Nima Sharifi, M.D.
Kendrick Family Chair for Prostate Cancer Research