Postdoctoral FellowThe University of Florida is seeking postdoctoral fellows interested in translational research and drug development. Our laboratory studies how two anticancer genes, BRG1 and BRM are silenced. BRG1 and BRM are catalytic subunits of the SWI/SNF complex, which promotes gene expression by remodeling the chromatin. Since many transcription factors and key cellular proteins required the SWI/SNF complex for their function, it is not surprising that this complex is inactivated during cancer development. Such proteins as Rb and p53 are functionally dependent on BRG1 and BRM and hence their function is impaired with BRG1 and/or BRM loss. We have found that BRM is not mutated by reversibly silenced and can be pharmacologically restored. As BRM and BRG1 re-expression inhibits cancer cell growth, reactivating these proteins is a novel form of targeted therapy. To this end, we have undertaken high throughput screening to identify novel compounds which can induce BRM. In addition, we have uncovered two 6bp insertational polymorphisms in the BRM promoter region which are tied to BRM silencing. As BRM loss promotes cancer development, we have found that these polymorphisms are predictive of cancer risk as well as patient outcome. Our research encompasses the pursuit of drug development, exploring biomarkers for cancer risk and understand the mechanisms of epigenetic silencing. Postdoctoral fellows will be involved in high throughput drug screening and in the validation of compound hits. Postdoctoral fellows must be well versed in molecular biology techniques such as western blotting, PCR, Q-PCR, cell culture, purification of nucleic acid and using and production of lentil virus. Postdoctoral fellow must be willing to work with mice as well. For a review of our research, see Oncogene April 2009. Salary range from $35-$45k depending on experience and ability. Please contact Dr. David Reisman M.D., Ph.D. at dnreisman@ufl.edu. Please forward CV and contact information for three references The large, well-equipped laboratory is located in the new Cancer Center at the University of Florida (Gainesville, Florida). Recent papers 1) Reisman D, Glaros S. and Thompson E.A. SWI/SNF and Cancer, 2009, Oncogene p1-16. 2009 Apr 9;28(14):1653-68. 2) Vanessa Gorden, Colin Rogers, David Reisman. Alterations in SWI/SNF in human cancers (2010) Oncology Reviews, 2010, Volume 4, Number 2, Pages 89-99 3) Sarah Gramling, David Reisman. Discovery of BRM Targeted Therapies: Novel Reactivation of an Anticancer Gene, Letters in Drug Design & Discovery. Vol 8, No. 1, January 2011 4) Liu G, Gramling S, Munoz D, Cheng D, Azad AK, Mirshams M, Chen Z, Xu W, Roberts H, Shepherd FA, Tsao MS, Reisman D. Two novel functional BRM insertion promoter polymorphisms, loss of BRM expression, and lung cancer risk. Oncogene. 2011 Jul 21;30(29):3295-304 5) Gramling S, Rogers C, Liu G, Reisman D. Pharmacologic reversal of epigenetic silencing of the anticancer protein, BRM, a novel targeted treatment strategy Oncogene. 2011 Jul 21;30(29):3289-94. Contact: David Reisman Medicine University of Florida 2033 Mowry Rd Gainesville, FL 32611 United States Phone: 3522736000
