Molecular Mechanisms and Translational Investigations of Advanced Prostate Cancer

A postdoctoral position supported by the Howard Hughes Medical Institute and the National Cancer Institute is available in the laboratory of Dr. Nima Sharifi at the Cleveland Clinic.

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 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 have also 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

The candidate should hold a doctoral degree with a background in molecular biology, metabolism or cancer biology.