Sylvester Comprehensive Cancer Center

Zafar Nawaz, Ph.D.

Zafar Nawaz, Ph.D.

Senior Associate Dean, Office of Graduate & Postdoctoral Studies; Professor of Biochemistry & Molecular Biology; Associate Research Director, Braman Family Breast Cancer Institute at Sylvester

Description of Research

Dr. Nawaz’s laboratory comprises of two arms of research: Cancer and Neuroscience Research. On the Cancer Research front, 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. On the Neuroscience Research front, Dr. Nawaz’s group is studying the transcriptional co-activation function of E6-AP in various Neuro-developmental and Neuro-Aging diseases. Dr. Nawaz’s laboratory has established that this less studied function of E6-AP is indeed an integral part of the pathobiology of a neurogenetic disease called Angelman Syndrome. This state of the art research has led his team to pursue exciting venues for the development of novel, non-invasive and affordable molecular tests to screen and diagnose such devastating neurological diseases.

Highlights

  • 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.
  • Discovered that E6-AP’s transcriptional coactivation function is an integral part of the pathobiology of Angelman Syndrome.
  • Developed novel molecular tests for the screening and diagnosis of Angelman Syndrome.

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. Read more »

Programs

Collaborating in the Multidisciplinary Research Program(s):

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