Molecular Mechanisms and Translational Investigations of Advanced Prostate Cancer

A postdoctoral fellowship position supported by Prostate Cancer Foundation and the National Cancer Institute 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 androgen deprivation therapy and the translational relevance thereof. Areas of interest in this laboratory 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, an FDA-approved drug, works by conversion to a more active steroidal metabolite (Li, et al. Nature. 2015 In press). We are currently working toward defining the relationship between metabolite generation and treatment response in patients with prostate cancer 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.

We previously 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 commonly in all models and patient tumors tested (Chang, et al. Proc Natl Acad Sci USA. 2011 Aug 16;108(33):13728-33). Our unprecedented approach to the identification of metabolic pathways in tumors from patients redefines the fundamental mechanism that drives the progression of resistant tumors. This work was featured as a Research Highlight in Nature Reviews Urology (Nat Rev Urol. 2011 Sep 8;8(9):470) and given a “must read” review by the Faculty of 1000 (http://f1000.com/13200029).

The position will provide a unique and multidisciplinary exposure to tumor metabolism, molecular oncology, drug development and clinical trials. This research program is supported by the Howard Hughes Medical Institute, the American Cancer Society, the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Research Program and the National Institutes of Health. 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