Education:
BSc 1970 Chemistry/Physiology - University of Potchefstroom, South Africa
BSc(Hon.) 1972 Biochemistry - University of Potchefstroom, South Africa
MSc 1973 Med. Biochemistry - University of Stellenbosch, South Africa
PhD 1977 Med. Biochemistry - University of Stellenbosch, South Africa
Postdoctoral Research Fellowship:
1978 Hadassah University Hospital, Israel
Started at USC: 1989 Research Topics: Cancer Genetics, Signal Transduction, Endocrinology/Metabolism, Molecular Epidemiology, Gene Regulation/Transcription
Research Description
Gerhard (Gerry) A. Coetzee, Ph.D.
Associate Professor of Urology, Preventive Medicine and Molecular Microbiology & Immunology
Research Topics: Cancer Genetics, Endocrinology, Steroid Receptors, and Transcription
The androgen receptor (AR) signaling axis is involved in all phases of prostate cancer (PCa), including the development of resistance to androgen ablation therapies. In contrast to breast cancer, where both estrogen receptor-positive and -negative tumors are found, prostate tumors are almost always AR positive, even during so-called androgen-independent phases of the disease. Resistance to androgen ablation therapies is not due to a loss of androgen sensitivity but rather results from increased AR activity and sensitivity. Our laboratory is concentrating on how the AR is mechanistically involved in the transition to ablation-resistance by analyzing the network of controls that determine the life-history of the AR, including where and how it contacts DNA and how it modulates gene expression. We have discovered a novel maturation pathway for the receptor and have identified many AR-occupied regions across the entire human genome. Both projects are yielding data that are changing existing paradigms of AR-mediated gene expression. Therefore, whereas ablation-resistant PCa represents the fatal form of the disease and whereas there is a dearth in the understanding of molecular mechanisms leading to the transition to this state, our work is yielding molecular information to clarify mechanisms involved in this transition. Because few treatment options exist for PCa once it has reached ablation resistance, our work will also significantly impact efforts to provide a rationale for therapeutic designs to treat patients with fatal ablation-resistant disease. More recently we have discovered novel AR-mediated enhancers at a distance from the genes they control.
10 Selected Publications:
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Baniwal SK,Khalid O,Sir D,Buchanan G,Coetzee GA,Frenkel B - Repression of Runx2 by Androgen Receptor (AR) in Osteoblasts and Prostate Cancer Cells: AR Binds Runx2 and Abrogates its Binding to DNA. - Mol Endocrinol [2009] Apr 23;(): PubMed
Berman BP,Frenkel B,Coetzee GA - Location, location, (ChIP-)location! Mapping chromatin landscapes one immunoprecipitation at a time. - J Cell Biochem [2009] Mar 23;(): PubMed
Jariwala U,Cogan JP,Jia L,Frenkel B,Coetzee GA - Inhibition of AR-mediated transcription by binding of Oct1 to a motif enriched in AR-occupied regions. - Prostate [2009] Mar 1;69(4):392-400 PubMed
Jia L,Berman BP,Jariwala U,Yan X,Cogan JP,Walters A,Chen T,Buchanan G,Frenkel B,Coetzee GA - Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity. - PLoS ONE [2008] ;3(11):e3645 PubMed
Khalid O,Baniwal SK,Purcell DJ,Leclerc N,Gabet Y,Stallcup MR,Coetzee GA,Frenkel B - Modulation of Runx2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer. - Endocrinology [2008] Dec;149(12):5984-95 PubMed
Buchanan G,Ricciardelli C,Harris JM,Prescott J,Yu ZC,Jia L,Butler LM,Marshall VR,Scher HI,Gerald WL,Coetzee GA,Tilley WD - Control of androgen receptor signaling in prostate cancer by the cochaperone small glutamine rich tetratricopeptide repeat containing protein alpha. - Cancer Res [2007] Oct 15;67(20):10087-96 PubMed
Prescott J,Jariwala U,Jia L,Cogan JP,Barski A,Pregizer S,Shen HC,Arasheben A,Neilson JJ,Frenkel B,Coetzee GA - Androgen receptor-mediated repression of novel target genes. - Prostate [2007] Sep 15;67(13):1371-83 PubMed
Jariwala U,Prescott J,Jia L,Barski A,Pregizer S,Cogan JP,Arasheben A,Tilley WD,Scher HI,Gerald WL,Buchanan G,Coetzee GA,Frenkel B - Identification of novel androgen receptor target genes in prostate cancer. - Mol Cancer [2007] Jun 6;6():39 PubMed
Jia L,Shen HC,Wantroba M,Khalid O,Liang G,Wang Q,Gentzschein E,Pinski JK,Stanczyk FZ,Jones PA,Coetzee GA - Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells. - Mol Cell Biol [2006] Oct;26(19):7331-41 PubMed
Saito Y,Liang G,Egger G,Friedman JM,Chuang JC,Coetzee GA,Jones PA - Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. - Cancer Cell [2006] Jun;9(6):435-43 PubMed
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