Zhongsheng You, Ph.D.
Assistant Professor
Cell Biology and Physiology
Assistant Professor
Internal Medicine
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Biochemistry Program
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Office Phone: 314-362-9893
Lab Phone: 314-362-4668
Other Phone: 314-422-5223 (cell)
FAX: 314-362-7463
Box: 8228
Lab Address: McDonnell Sciences Building, Room 514
Email: zyou@wustl.edu
Website: http://under construction
Keywords: cancer; cell cycle; chromatin; DNA damage; laser micro-irradiation; Xenopus egg extracts
Short Research Description: Molecular mechanisms of genome surveillance and tumorigenesis |
Research Abstract:
Research in our group focuses on understanding genome surveillance and repair systems and how defects in these systems lead to cancer. A major effort in the lab is to investigate how cells maintain the integrity and stability of the genome when the most dangerous type of DNA damage, DNA double-strand breaks, occur in chromatin. We employ multiple experimental systems, including Xenopus egg extracts and human cells, to dissect the mechanisms and regulation of DNA surveillance and repair networks. In addition, we utilize a “laser scissors” technology in combination with advanced imaging tools to visualize the DNA damage response in individual cells. Currently, we are pursuing the following fundamental questions:
1. How do cells read the DNA damage signal? We investigate the molecular mechanisms by which proteins such as the Mre11-Rad50-NBS1 complex sense DNA double-strand breaks in chromatin. We also are seeking the nature of the chromatin domains flanking the DNA break ends and their role in promoting DNA damage sensing.
2. How do cells translate the DNA damage signal into downstream checkpoint response? Cells that experience DNA damage respond by activating a checkpoint which stops the cell cycle until the damage can be repaired. Activation of the atypical protein kinases ATM and ATR is key to the conversion of the DNA damage signal into downstream checkpoint signaling events. We are extending our study on how the recognition and processing of DNA double-strand breaks lead to activation of these kinases and downstream cell signaling.
3. How do cells orchestrate various DNA damage signaling pathways in order to promote maintenance of genome integrity? DNA double-strand breaks activate a plethora of cellular responses, such as checkpoint-mediated cell cycle arrest, DNA repair and transcriptional reprogramming. We investigate the functional interplays between these biological responses and the importance of coordination of these processes in preserving genome stability.
We are also interested in identifying and characterizing new components of the DNA surveillance and repair networks using genomics and proteomics tools. By understanding the basic mechanisms of genome maintenance, we hope to contribute to understanding of the process of tumorigenesis and the development of new cancer therapeutics. |
Selected Publications:
You Z, Bailis J, Johnson S, Dilworth S and Hunter T. Rapid Activation of ATM on DNA Flanking Double-Strand Breaks, Nature Cell Biology 2007 9:1311-1318.
You Z*, Chahwan C*, Bailis J, Hunter T and Russell P. ATM Activation and Its Recruitment to Damaged DNA Require Binding to the C-Terminus of Nbs1. Molecular and Cellular Biology 2005 25:5363-5379.
You Z, Harvey K, Kong L and Newport J. Xic1 Degradation in Xenopus Egg Extracts Is Coupled to Initiation of DNA Replication. Genes and Development 2002 16:1182-1194.
You Z, Kong L and Newport J. The Role of Single-stranded DNA and Pol alpha in Establishing the ATR, Hus1 DNA Replication Checkpoint. Journal of Biological Chemistry 2002 277: 27088-27093.
Hekmat-Nejad M*, You Z*, Yee M, Newport J and Cimprich K. Xenopus ATR is a Replication-dependent Chromatin-binding Protein Required for the DNA Replication Checkpoint. Current Biology 2000 10:1565-1573. |