Zafar Nawaz, Ph.D.

Associate Professor, Biochemistry and Molecular Biology Department

Associate Research Director, Braman Family Breast Cancer Institute

Research Interests

Dr. Nawaz’s research focuses on mechanisms of steroid hormone receptor and coactivator action in normal and cancerous tissues, with important emphasis on estrogen receptor (ER) regulation in breast cancer and androgen receptor (AR) regulation in prostate cancer. Steroid hormones are important regulators of cell growth and influence cancer development, exerting biological effects on target tissues through intracellular receptor proteins. Coactivators positively influence steroid hormone receptor-mediated transcription. Dr Nawaz was among the first to show that the ER is ubquitinated and that ligand binding activates rapid steroid hormone receptors proteolysis via the ubiquitin-proteasome pathway. For certain receptors, this is required for their proper functioning.

He went on to show thatan E3 ubiquitin-protein ligase enzyme named E6-associated protein (E6-AP) and an E2 ubiquitin-conjugation enzyme, UbcH7, both act as coactivators of steroid hormone receptors. Dr. Nawaz is studying the role of E6-AP and UbcH7 in the regulation of steroid hormone receptors protein stability, steroid hormone receptor-dependent gene transactivation and breast and prostate carcinogenesis. Dr. Nawaz’s laboratory has developed mammary gland specific E6-AP transgenic mice and stable in vitro cell line models to further investigate the role of E6-AP in breast carcinogenesis and progression. Using prostate transgenic mouse lines and in vitro stable cell lines, they have also shown that E6-AP influences normal prostate gland development and prostate tumorigenesis by modulating the levels and functions of AR, apoptosis and cell signaling pathways. Using these models Dr. Nawaz’s laboratory is learning about the factors and pathways that are responsible for the development of breast and prostate cancers. This will be helpful in designing novel smart drugs for treatment of these hormone responsive cancers.

Representative Publications:

• S.  Dhananjayan and Z. Nawaz. Ubiquitin and the control of transcription. 2005. Assays in Biochem., 41, 69-80.

• J. Wu, Y. Liang, Z. Nawaz, and S. M. Hyder. 2005. Complex agonist-like properties of ICI 182,780 (Faslodex) in human breast cancer cells that predominantly express progesterone receptor-B: implications for treatment resistance. Int J Oncol. 27(6):1647-59 

• O. Y. Khan, G. Fu, A. Ismail, S.  Srinivasan, X. Cao, Y. Tu, S. Lu, and Z. Nawaz. 2006. Multifunction steroid receptor coactivator, E6-associated protein, E6-AP is involved in development of the prostate gland. Mol. Endocrinol. 20, 544-559.

• S.  C. Dhananjayan, S. Ramamoorthy, O. Y. Khan, A. Ismail, J. Sun, J. Slingerland,  B. W. O'Malley, and Z. Nawaz. 2006. WW-domain binding protein-2 (WBP-2), an E6-AP interacting protein acts as a coactivator of estrogen and progesterone receptors. Mol Endocrinol., 20 (10): 2343-2354.

• P.  B. Rapuri, J. C. Gallagher, and Z. Nawaz. Caffeine decreases vitamin D receptor protein expression and 1,25(OH)(2)D(3) stimulated alkaline phosphatase activity in human osteoblast cells. J Steriod Biochem Mol Biol. 2007 Jan. 11; [Epub ahead of print].

Honors and Awards:

Honorary Member The Endocrine Society

Honorary Member American Society of Microbiology

Honorary Member The American Cancer Society

Honorary Member American Association for the Advancement of Science