Youwei Zhang, Ph.D.
W343A Wood Building
Genome stability, in a simple way, means that the genetic information buried in DNA has to be kept stable. Changes or damages to DNA, if not fixed, often lead to the loss of genome stability. A long-term effect of the loss of genome stability is the occurrence of degenerative diseases, including premature ageing and human cancers. My lab is trying to understand a fundamental biological issue: how the genome stability is maintained in human cells? In detail, we focus on dissecting the molecular signaling networks that maintain the genome stability in human cells.
Virtually every function of the cell is carried out by a number of proteins that form a network within the cell. Genome stability maintenance is no exception. Knowing members of this signaling network is critical for our understanding of how the genome stability is maintained in human cells. We use biochemical, genetic, pharmacological and structural tools to identify proteins involved in this process and characterize their molecular function. In the long, we wish to understand how the genome stability is maintained.
The genome stability maintenance network functions as a double-edge sword. At one hand, it protects the cell's DNA from damage. On the other hand, it has remained a central target in cancer therapy. The idea underpinning this strategy is that inhibiting the genome stability maintenance network makes cancer cells extremely sensitive to agents that damage their DNA, enhancing the cell killing effect. Our laboratory is also interested in translate the knowledge that we gained above from bench to bed. The long-term goal is to cure or control cancers to increase the quality of life.
Therapeutic Advances and Research Breakthroughs
Studies done in my lab have the potential to be translated into potential treatment for human diseases, including cancers. For instance, our latest discovery opened the door for a new way to treat cancers without the concurrent use of chemotherapeutic drugs. Therefore, this novel concept should significantly reduce the toxic side effect by chemotherapy (see detail at:http://www.cancer.gov/newscenter/cancerresearchnews/2012/GeneThatStopsCancerCellProliferation). We wish to design a better therapy for cancer patients with more effect and less toxicity.
Jingna Wang, Xiangzi Han, and Youwei Zhang*. Auto-regulatory mechanisms of phosphorylation of checkpoint kinase 1 (Chk1). Cancer Research, 72, 3786-3794, 2012.
Jingna Wang, Xiangzi Han, Xiujing Feng, Zhenghe Wang, and Youwei Zhang*. Coupling cellular localization and function of Chk1 in checkpoints and cell viability. Journal of Biological Chemistry, 287, 25501-25509, 2012.
Amitabha Chakrabarti, Kalpana Gupta, Abigail Glick, Youwei Zhang, Munna Agarwal, Mukesh K Agarwal and David N Wald. ATP depletion triggers AML differentiation through an ATR-Chk1 dependent and p53 independent pathway. Journal of Biological Chemistry, 287, 23635-23643, 2012.
John Brognard, You-Wei Zhang, Lorena Puto, and Tony Hunter. Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor suppressing kinase. Cancer Research, 71, 3152-3161, 2011.
Jingna Wang, Staci Engle, Callie Merry, and You-Wei Zhang*. A new in vitro system for activating the cell cycle checkpoints. Cell Cycle, 10, 500-506, 2011.
Callie Merry, Jingna Wang, Kang Fu, I-Ju Yeh, and You-Wei Zhang
. Targeting Chk1 in cancer therapy. Cell Cycle, 9, 1-5, 2010.
Zhongsheng You, Linda Z. Shi, Quan Zhu, Peng Wu, Youwei Zhang,
Andrew Basilio, Nina Tonnu, Inder Verma, Michael W. Berns, and Tony Hunter. CtIP
Links DNA Double-strand Break Sensing to Resection. Molecular Cell, 36, 954-969,
You-Wei Zhang, John Brognard, Chris Coughlin, Zhongshen You, Marisa
Dolled-Filhard, Aaron Aslanian, Gerard Manning, Robert T. Abraham, and Tony Hunter.
The F-box protein Fbx6 regulate Chk1 stability and cellular sensitivity to replication
stress. Molecular Cell, 35, 442-453, 2009.
You-Wei Zhang, Tony Hunter, and Robert T. Abraham. Turning the
Replication Checkpoint On and Off. Cell Cycle, 5, 125-128, 2006.
You-Wei Zhang, Dianne M. Otterness, Gary G. Chiang, Yuncai Liu,
Weilin Xie, Frank Mercurio, and Robert T. Abraham. Genotoxic Stress Targets Human
Chk1 for Degradation by the Ubiquitin-Proteasome Pathway. Molecular Cell,
19, 607-618, 2005.
You-Wei Zhang, Makoto Kaneda, and Ikuo Morita. A gap junction-independent
tumor suppressing effect of connexin 43. Journal of Biological Chemistry
278, 44852-44856, 2003.
You-Wei Zhang, Keiko Nakayama, Kei-Ichi Nakayama, and Ikuo Morita.
A Novel Route for Connexin 43 to Inhibit Cell Proliferation: Negative Regulation
of Skp2. Cancer Research 63, 1623-1630, 2003.
You-Wei Zhang, Ikuo Morita, Masa-aki Ikeda, Kai-Wen Ma, and Sei-itsu
Murota. Connexin 43 suppresses proliferation of osteosarcoma U2OS cells through
posttranscriptional regulation of p27. Oncogene 20; 4138-4149, 2001.
You-Wei Zhang, Ikuo Morita, Masamichi Nishida, and Sei-itsu Murota.
Involvement of tyrosine kinase in the hypoxia/reoxygenation-induced gap junctional
intercellular communication abnormality in cultured human umbilical vein endothelial
cells. Journal of Cellular Physiology 180; 305-313, 1999.
Ikuo Morita, You-Wei Zhang, and Sei-itsu Murota. Eicosapentaenoic
acid (EPA) protects endothelial functions injured by hypoxia/reoxygenation. Ann.
N. Y. Acad Sci. 947: 394-397, 2001.