 |
| |  Zafar Nawaz, Ph.D. Professor, Department of Biochemistry & Molecular Biology and Senior Associate Dean for Graduate and Postdoctoral Studies (305) 243-1456 (office) Biomedical Research Bldg. #723 ZNawaz@med.miami Link to Collexis Profile
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.
Major Discoveries:
- Discovered protein degradation is linked to steroid hormone receptor gene transcription. Unraveling this mechanism suggests that proteasome inhibitors can be developed into therapeutic agents for breast and prostate cancers.
- Discovered novel proteins that regulate the functions of steroid hormone receptors. This discovery will be helpful in designing novel smart drugs for treatment of breast and prostate cancers.
- Developed novel animal model systems for breast and prostate cancers. These models will be useful to study the molecular biology of the breast and prostate tumorigenesis.
|
- 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 S.V., Zhang Y., Pledger J.W., Chen J. and Bai W. 2009. MDM2 Acts Downstream of p53 as an E3 Ligase to Promote FOXO Ubiquitination and Degradation. J Biol Chem. 284(21):13987-4000.
- Ramamoorthy, S., and Nawaz, Z. 2008. E6-associated protein is a dual function coactivator of steroid hormone receptors. The Nuclear Receptor Signaling. 6:e006.
- Chu I., Arnaout A., Loiseau S., Sun J., Seth A., McMahon C., Chun K., Hennessy B., Mills G.B., Nawaz Z. and Slingerland J. 2007 Src promotes estrogen-dependent estrogen receptor alpha proteolysis in human breast cancer. J Clin Invest.; 117(8):220
- Dhananjayan S.C., Ramamoorthy S., Khan O.Y., Ismail A., Sun J., Slingerland J., O'Malley B.W., and Nawaz Z.. (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):2343-54.
- Khan O.Y., Fu G., Ismail A., Srinivasan S., Cao X., Tu Y., Lu S. and Nawaz Z. (2006) Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. Mol Endocrinology, 20(3):544-59.
|
Back to Previous Page
|
|
|
