Molecular Mechanisms and Translational Investigations of Advanced Prostate Cancer

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 Lerner Research Institute in the Department of Cancer Biology.

Our laboratory is focused on 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 androgen synthesis

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 recently discovered that abiraterone works by conversion to a more active steroidal metabolite (Li, et al. Nature. 2015 523(7560):347-51). We are currently working toward defining the relationship between metabolite generation and treatment response in patients and identifying new chemical entities that are determinants of treatment response.

We also 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). We are pursuing similar mechanisms and developing new treatment modalities based on these discoveries. Our work was featured in an “Editor’s Choice” in Science Translational Medicine and a “Research Watch” in Cancer Discovery.

Previously, we discovered that prostate cancer becomes resistant to hormonal therapy by the synthesis of dihydrotestosterone through a pathway that circumvents testosterone, instead requiring 5α-androstanedione, a previously underappreciated intermediate metabolite. This metabolic pathway occurs in patient tumors (Chang, et al. Proc Natl Acad Sci USA. 2011 Aug 16;108(33):13728-33).

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, 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
sharifn@ccf.org