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Urology Research Laboratory
Harrison Department of Surgical Research
Dr. Samuel K. Chacko
 
Research Personnel
 
William J. Fredericks, Ph.D.

Current Projects

Research Assistant Professor
Division of Urology, Department of Surgery
University of Pennsylvania School of Medicine
VA Medical Center Philadelphia
Laboratory of Dr. Bruce Malkowicz
University Ave. and Woodland Ave.
Research Building 21, Room A418
Philadelphia, PA 19104
Lab Phone: 215-823-4546
Fax: 215-823-5171
Email: William.Fredericks@uphs.upenn.edu
Email: wjfredericks@verizon.net

 
Education
  • Cornell University, Ithaca, NY, B.S. Biological Sciences, Physiology, 1981.
  • Roswell Park Memorial Institute, Ph.D. 1991. SUNY Buffalo, NY. Department of Pharmacology and Experimental Therapeutics, Thesis: P-Glycoprotein Expression in Cell Lines, Human Solid Tumors, and Normal Tissues.
  • Wistar Institute, Philadelphia, PA, , Postdoctoral Research Fellow, Dr. F. Rauscher III Targeted malignant phenotype suppression with an engineered transcriptional repressor.
 
Research Interests

The role of TERE1/UBIAD1 and associated proteins in the progression of bladder and prostate cancer. The current focus is TERE1-mediated modulation of cholesterol homeostasis and its effects on tumor signal transduction, proliferation, apoptosis, and as a determinant of intacrine growth mechanisms. The approach applies molecular tools to establish cellular models for correlation with findings in human specimens and mice. The goal is to discover and exploit the mechanisms tumors use to escape normal regulation.

General Interests: Molecular Mechanisms of Oncology: transcription factors, tumor suppression, progression, drug resistance and metastasis. Mechanisms of gene regulation, transcriptional repression, epigenetic regulation, DNA repair. Protein interactions and modifications in sub-cellular targeting, signaling and regulation of gene expression. Protein structure and domain modularity and engineering. Array analysis of disease gene pathways.

 
Lab Rotation Projects
Motivated students are welcome to visit us anytime to discuss available projects within the laboratory of Dr. Malkowicz.
 
Bibliography - Selected Publications
  1. Tank DW, Fredericks WJ, Barak LS, Webb WW. Electric field-induced redistribution and postfield relaxation of low density lipoprotein receptors on cultured human fibroblasts. J Cell Biol 101(1):148-157, July 1985.
  2. Baker RM, Fredericks WJ, Chen YF. Detection of P-glycoprotein in human tumors. Cancer Invest 8(2):255-256, 1990.
  3. Fredericks WJ, Galili N, Mukhopadhyay S, Rovera G, Benicelli J, Barr F, Rauscher FJ III. The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcoma is a more potent transcriptional activator than PAX3. Mol Cell Biol 15(3):1522-1535, Mar. 1995.
  4. Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang X-P, Neilson EG, Rauscher III FJ. KAP-1: A novel co-repressor for the highly-conserved KRAB repression domain. Genes & Development 10(16):2067-2078, Aug. 15, 1996.
  5. Fredericks WJ, Ayyanathan K, Freidman JR, Herlyn M, Rauscher III FJ. An engineered PAX3-KRAB transcriptional repressor inhibits the malignant phenotype of alveolar rhabdomyosarcoma cells harboring the PAX3-FKHR oncogene. Mol Cell Biol 20(14):5019-5031, July 2000.
  6. Ayyanathan K, Fredericks WJ, Berking C, Herlyn M, Gunther E, Balikrishnan, Rauscher III FJ. Hormone dependent tumor regression in vivo by an inducible transcriptional repressor directed at the PAX3-FKHR oncogene. Cancer Research 60(20):5803-5814, Oct. 15, 2000.
  7. Fredericks WJ, Kasirajan A, Rauscher III FJ. Regulating the neoplastic phenotype using engineered transcriptional repressors. Cancer Letters 162(Suppl): S23-S32, Jan. 2001.
  8. Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher III FJ, Chen J. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO Journal 24(16): 3279-3290, Sep 21, 2005.
  9. Ayyanathan K, Peng P, Hou Z, Fredericks WJ, Goyal RK, Langer EM, Longmore, GD, and Rauscher, FJ III The AJUBA LIM Domain Protein is a Co-Repressor for SNAG Domain Mediated Repression and Participates in Nucleo-Cytoplasmic Shuttling. Cancer Research 67(19): 9097-106. Oct 1, 2007.
  10. Ivanov A, Peng H, Yurchenko V, Yap, KL, Negorev, DG, Schultz, DC, Psulkowski, E, Fredericks, WJ, White, DE, Maul, GG. Sadofsky, MJ. Zhou, MM. and Rauscher, FJ III1,PHD Domain-Mediated E3 Ligase Activity Directs Intramolecular Sumoylation of an Adjacent Bromodomain Required for Gene Silencing, Molecular Cell 28(5):823-37. Dec 14, 2007.
  11. Abstracts (recent)
    Fredericks WJ, Wang H, Zheng Y, Boyer J, Schullery D, Aqui N, Lal, P, Tomaszewski J, McGarvey T, Malkowicz SB. Elevated TERE1 protein induces cytokine expression in J82 bladder cancer and human immune cells. AUA Orlando, FL 2008.
  12. Fredericks WJ, Wang H, Sepulveda J, McGarvey T, Malkowicz SB. TERE1/UBAID1 and TBL2 proteins Regulate cholesterol levels in bladder cancer cells. Accepted AUA Chicago, 2009.
 
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