Drug Discovery for Advanced Prostate Cancer

A postdoctoral fellowship position for drug discovery is available in the laboratory of Dr. Nima Sharifi at the Cleveland Clinic in the Department of Cancer Biology.

Our laboratory and translational research program is focused on metabolic and molecular mechanisms of androgen synthesis and androgen receptor (AR) gain-of-function that lead to resistance to hormonal therapy.

A postdoctoral fellowship is available for drug discovery against a newly credentialed molecular target against prostate cancer. The candidate will take a leading role in the development of a compound screening assay for the identification and validation of a lead inhibitor compound against the molecular target, defining the mechanism of compound interaction with the target and optimizing the properties and potency of the lead compound.

The ideal candidate has a Ph.D. degree in biochemistry, chemistry or molecular biology and has the appropriate expertise that can be applied to drug development. Outstanding verbal and communication skills are required.

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), that we have shown drives poor outcomes after hormonal therapy (Hearn, et al. Lancet Oncol. 2016 17(10):1435-44; Hearn, et al. JAMA Oncol. 2017 Oct 12), yet serves as a tumor vulnerability to alternative steroid ablation inhibitors (Almassi, et al. JAMA Oncol. 2017 Oct 12).
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), and that this is a class effect of steroidal androgen synthesis inhibitors (Alyamani, et al. Cell Chemical Biology. 2017 24, 1-8, July 20).

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 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
casalek@ccf.org