Department of Medical Microbiology and Immunology, School of Medicine
Prostate cancer, Bladder Cancer, transcription factors, Androgen Receptor
Hormonally regulated malignancies are treated with endocrine therapies which specifically target a hormone receptor to arrest tumorigenesis. In prostate cancer, the androgen receptor (AR) is pivotal regulator key cellular function by controlling transcription of genes that ensure cell viability. AR signaling requires optimal AR signaling where sub or supraphysiological levels are detrimental to cell viability. While the mechanism of androgen depletion are well studies, the mechanisms that hinder tumorigenesis due to supraphysiological androgen levels are not well understood. We have found that the tumor suppressor p14ARF is involved in this process. One focus of the lab is aimed a leveraging this finding to identify pharmachological targets. The second focus of the lab is on bladder cancer. While not traditionally considered a hormonally regulated malignancy, bladder cancer is affected by hormones, specifically by androgens. Studies in our laboratory found that most bladder cells harbor AR splice variants that are constitutively active, and that depletion of these variants results in cell death. Our goal is to identify how AR promotes cell viability and identify proteins that can be targeted to limit tumorigenesis.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Integrative Genetics and Genomics
Specialties / Focus
- Chromosome Biology
- Genomics, Proteomics and Metabolomics
- Human Genetics and Genomics
- Molecular Medicine
- American Association for Cancer Research
- Society for Basic Urologic Research
- 1977 BS Biology Johns Hopkins University
- 1987 PhD Genetics George Washington University
Han Bit Baek, Alan Lombard, Stephen Libertini, Aleida Fernandez-Rubio, Ruth Vinall, Regina Gandour-Edwards, Rachel Nakagawa, Kathleen Vidello, Kristine Nishida, Hiromi Wettersten, Yosef Landesman, Robert H. Weiss, Paramita M. Ghosh, Maria Mudryj. XPO1 inhibition by Selinexor induces potent cytotoxicity against high grade bladder malignancies. (2018) Oncotarget, 9 (77), 34567-34581.
Leandro S. D’Abronzo, Michael E. Crapuchettes, Ryan E. Beggs, Ruth L. Vinall, Clifford G. Tepper, Salma Siddiqui, Maria Mudryj, Frank E. Melgoza, Blythe P. Durbin-Johnson, Ralph W. deVere White and Paramita M. Ghosh. The Androgen Receptor is a negative regulator of eIF4E Phosphorylation at S209: Implications for the use of mTOR inhibitors in advanced prostate cancer. ( 2017) Oncogene, 46, 6359-6373.
Alan P. Lombard and Maria Mudryj. The Emerging role of the androgen receptor in bladder cancer. Endocrine-related cancer. 2015 Jul 30. pii: ERC-15-0209. [Epub ahead of print]
2015 Alan P. Lombard, Rebecca Lim, Rachel Nakagawa, Kathleen Vidallo, Stephen J. Libertini, Alexander J. Platero, Maria Mudryj. Dicer Ablation Promotes a Mesenchymal and Invasive Phenotype in Bladder Cancer Cells. (2015) Oncology Reports Jul 9. doi: 10.3892/or.2015.4117.
Alan P. Lombard, Benjamin Mooso, Stephen J. Libertini, Rebecca Lim, Rachel Nakagawa, Kathleen Vidello, Nicole Constanzo. Paramita M. Ghosh, Maria Mudryj. MiR-148a dependent apoptosis of bladder cancer cells is mediated by the epigenetic modifier DNMT1. Molecular Carcinogenesis 11 APR 2015 | DOI: 10.1002/mc.22319
Rosalinda M. Savoy, Liqun Chen, Salma Siddiqui, Frank U. Melgoza, Blythe Durbin-Johnson, Christiana Drake, Maitreyee K. Jathal, Swagata Bose, Thomas M. Steele, Benjamin A. Mooso, Leandro S. D’Abronzo, William H. Fry, Kermit L. Carraway, III, Maria Mudryj, and Paramita M. Ghosh. Transcription of Nrdp1 by the androgen receptor is regulated by nuclear Filamin A in prostate cancer. Endocrine-related Cancer 2015 Mar 10. pii: ERC-15-0021. [Epub ahead of print]