Research Knowledgebase

Zafar Nawaz, Ph.D. Associate Professor of Biochemistry & Molecular Biology View full faculty profile

Description of Research

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 receptors. Coactivators positively influence steroid hormone receptor-mediated transcription. Dr. Nawaz’s research group was among the first to show that ER is ubiquitinated and that ligand binding activates rapid steroid hormone receptor proteolysis via the ubiquitin-proteasome pathway. For certain receptors such as ER and AR proteasome-dependent degradation is required for their proper functioning. Dr. Nawaz’s research group went on to show that an 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.

Currently, Dr. Nawaz’s research group is studying the role of E6-AP and UbcH7 in the regulation of steroid hormone receptors protein stability, steroid hormone receptor-dependent gene transactivation with emphasis on breast and prostate carcinogenesis. In order to identify the genes that are either activated or repressed by E6-AP in the breast carcinoma cells, Dr. Nawaz’s laboratory is utilizing the state-of-the-art technique known as chromatin immunoprecipitation followed by microarray or genome wide location analysis. The data from this analysis will give researchers a global perspective of the different functions of E6-AP, and help to better understand the specific role of E6-AP’s involvement in cellular pathways in the breast. To further investigate the role of E6-AP in breast carcinogenesis and progression, Dr. Nawaz’s laboratory has developed and is utilizing mammary gland specific E6-AP transgenic mice and stable in vitro cell line models. Using prostate transgenic mouse lines and in vitro stable cell lines, Dr. Nawaz’s group also has 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 responsible for the development of breast and prostate cancers. Dr. Nawaz’s group also has identified WW-domain binding protein 2 (WBP-2) as an E6-AP interacting protein, and has shown it acts as a coactivator of certain steroid hormone receptors. Presently, Dr. Nawaz’s research group is examining the mechanism by which WBP-2 regulates functions of steroid hormone receptors and its role in breast carcinogenesis. All of these studies will be helpful in designing novel smart drugs for treatment of breast and prostate cancers.

Selected Cancer-Related Publications

Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, Nawaz Z, Shimojima T, Wang H, Yang Y, Shen Z, Zhang Y, Zhang X, Nicosia SV, Zhang Y, Pledger JW, Chen J, Bai W. MDM2 Acts Downstream of p53 as an E3 Ligase to Promote FOXO Ubiquitination and Degradation. J Biol Chem 284:13987-4000, 2009. PubMed link

Ramamoorthy S, Nawaz Z. E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors. Nucl Recept Signal 6:e006, 2008. PubMed link

Sun J, Nawaz Z, Slingerland JM. Long-Range Activation of GREB1 by Estrogen Receptor via Three Distal Consensus Estrogen-Responsive Elements in Breast Cancer Cells. Mol Endocrinol 21:2651-2662,2007. PubMed link

Rapuri PB, Gallagher JC, Nawaz Z. Caffeine decreases vitamin D receptor protein expression and 1,25(OH)(2)D(3) stimulated alkaline phosphatase activity in human osteoblast cells. J Steroid Biochem Mol Biol 103:368-71, 2007. PubMed link

For full description of Multidisciplinary Research Program(s), Genitourinary Malignancies Program, Breast Cancer Program.