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 UT Southwestern Medical Center.

Our laboratory is focused on molecular mechanisms of 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 have recently 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). We have also shown that blocking the enzyme 3β-hydroxysteroid dehydrogenase stops the androgen-response from adrenal precursors, validating this as a potential pharmacologic target for the treatment of advanced prostate cancer (Evaul, et al. Endocrinology. 2010. 151(8):3514-20). Furthermore, our most recent studies have demonstrated that alternative activities of drugs currently utilized in patients with advanced prostate cancer may be harnessed to reverse initial or acquired therapy resistance (Li, et al. Clin Cancer Res. 2012 July 1;18(13):3571-9).

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: http://www4.utsouthwestern.edu/sharifilab/index.html

UT Southwestern Medical Center is the home of five Nobel Laureates, 19 members of the National Academy of Sciences and 18 Members of the Institute of Medicine.

The candidate should hold a doctoral degree with a background in molecular biology, metabolism or cancer biology. Candidates with an interest in the position should send their cv and contact information for 3 references to:

Nima Sharifi, M.D.
Division of Hematology/Oncology
UT Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas, TX 75390-8852

c/o Hem/Onc Research HemOncResearch@utsouthwestern.edu

UT Southwestern Medical Center is an Equal Opportunity, Affirmative Action Employer