Hui Zhang, Ph.D.
Senior Scientific Member, Professor, Director of Cancer Cell Proteomics, Division of Basic Sciences
hzhang@nvcancer.org
Dr. Hui Zhang received his Ph.D. from the Johns Hopkins University School of Medicine in 1990. He was a postdoctoral associate at Harvard Medical School and the Howard Hughes Medical Institute at Cold Spring Harbor Laboratory from 1991-1995. In 1996, he established his own laboratory in the Department of Genetics, Yale University School of Medicine, rising to the rank of associate professor. He joined Nevada Cancer Institute in July 2007 as the director of Cancer Cell Proteomics.
Dr. Zhang is a renowned expert in cell cycle regulation, the control of DNA replication, genome stability and gene expression. He has made several seminal observations that have had significant impact in the field of oncology. He was the first to identify p16Ink4A and p21Cip1, two important CDK inhibitors that play central roles in suppression of cancer cell cycle and SKP2-containing SCF ubiquitin E3 ligase that targets another important CDK inhibitor p27Kip1 for cell cycle-dependent proteolysis. He also found that CDT1, an essential replication licensing protein, can induce endo-reduplication of DNA, i.e., re-replication without cell division, resulting in chromosome polyploidy and aneuploidy. In addition, he has shown that many WD40 repeat protein family members modulate the cell cycle, DNA replication, and gene expression by controlling the activities of ubiquitin E3 ligases and the proteosome. One of them, CDT2, a component of a novel ubiquitin E3 ligase that also contains CUL4 and DDB1, regulates CDT1 degradation to prevent chromosomal aneuploidy.
Recently Dr. Zhang found that CUL4-DDB1 regulates histone H3 methylation at lysine 4 (K4) by interacting with WDR40 repeat proteins WDR5 and RBBP5, essential components of histone H3 methyltransferases MLL (Mixed Lineage Leukemia) to activate gene expression. It was discovered that CUL4-DDB1 also interacts with WD40 repeat protein EED, which is a critical component of Polycomb histone H3 methyltransferase EZH2 complex that controls histone H3 methylations at lysines 9 and 27 (K9 and K27) for gene silencing, X-chromosomal inactivation, and genomic imprinting. These epigenetic regulations control gene expression patterns in somatic and stem cells, as well as regulation of DNA damage response and replication initiation. These processes are altered in many human cancers and Dr. Zhang’s research has identified many important and novel targets for cancer therapy.
Currently, Dr. Zhang is applying advanced technologies in proteomics and molecular genetics to identify the differences between normal and cancer cells and to establish pre-clinical disease models for mechanistic insights and for developing therapeutic strategies. Dr. Zhang’s laboratory is also actively developing approaches to translate these new findings to clinically useful applications for cancer diagnosis and treatment.
Recent publications
Zhang, H. (2010). Skip the nucleus, AKT drives Skp2 and FOXO1 to the same place? Cell Cycle, March 1, 9(5).
Wu, X.-H., Zhang, H., and Wu, Y.-D. (2009). Is Asp-His-Ser/Thr-Trp Tetrad Hydrogen-bond Network Important to WD40-repeat Proteins: A Statistical and Theoretical Study. PROTEINS: Structure, Function, and Bioinformatics (Johns Hopkins University Publication) 78, 1186-1194.
Liu, Y.-Q, Wen, X.-M., Lui, E L.H.., Friedman, S. L., Cui, W., Ho, N. P. S., Li, L., Ye, T., Fan, S.-T., and Zhang, H. (2009). Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258. Laboratory Investigation 89, 1152-1160.
Xiang, J., Yang, H.-B., Che, C., Zou, H.-X., Yang, H.-S., Chen, J.-H., Zhang, B., Wei, Y.-Q., Quan, J.-M., Zhang, H., Yang, Z., and Lin, S. (2009). Identifying Tumor Cell Growth Inhibitors by Combinatorial Chemistry and Zebrafish Assays. PLOS One 4, e4361.
