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Dr. Xuetong Shen

Dr. Xuetong Shen

Regular Member

The University of Texas MD Anderson Cancer Center
Department of Molecular Carcinogenesis
The Virginia Harris Cockrell Cancer Research Center

My laboratory is located in Smithville, Texas, at UT Science Park

We seek to answer basic questions concerning the regulation and maintenance of eukaryotic genome, which is organized into chromatin. ATP-dependent chromatin remodeling carried out by large protein complexes (SWI/SNF family) is recognized as a major mode of chromatin modification. The research in my lab focuses on understanding how chromatin is remodeled to suit various nuclear functions, such as transcription and DNA repair, and how defects in chromatin remodeling might lead to cancer. We use the budding yeast as a model system, taking advantage of the powerful genetics, as well as the well-developed biochemical tools. Depending on the student's interests, a tutorial in my laboratory would provide experience with biochemistry, yeast genetics, molecular biology and cell biology. Students will be given a choice from a wide range of projects demanding both biochemical and genetic approaches. Current research focuses on a novel and evolutionarily conserved class of ATP-dependent chromatin remodeling complexes, called the INO80 class. The study of the INO80 complex has led us to two main areas of research in the lab.

1. Chromatin Responses to DNA damage
Environmental exposures to DNA-damaging agents, and genetic changes within the cell can lead to a variety of DNA damage, which causes genome instability and can eventually result in human diseases such as cancer. However, in vivo, eukaryotic DNA is packaged into chromatin; therefore, the damaged DNA exists in the context of chromatin, and the DNA repair machinery must deal with the chromatin environment. Eukaryotic cells utilize chromatin modifying complexes to regulate chromatin by ATP-dependent perturbations of histone-DNA interactions, or by covalent post-translational modification (PTM) of the histones. The long-term goal of our research is to understand how chromatin is modified to allow DNA repair to occur in an orderly fashion after DNA is damaged, and how changes in chromatin modification lead to human diseases, such as cancer. We and others have shown that the INO80 complex is a direct and key player in the repair of DNA double-strand breaks (DSBs), thus establishing a link between chromatin remodeling and DNA repair. Additional studies from our lab have shown that the INO80 complex is post-translationally modified upon DNA damage. Based on these studies, we propose that chromatin undergoes complex changes in response to DNA damage, which involve not only the histones, but also the chromatin modifying complexes. Studying how chromatin responses to DNA damage will contribute to our understanding of the mechanisms of genome instability and carcinogenesis.
 
2. Nuclear Actin and Related Proteins
Recent advances in chromatin research have identified conventional actin, as well as actin-related proteins (Arps) as subunits of many chromatin modifying complexes. Like histones, actin is one of the most important and conserved molecules of the cell. While the roles of actin in the cytoplasm are well established, the presence and function of actin in the cell nucleus remain poorly defined. The mystery of nuclear actin has remained a challenge to biologists for several decades, due to the lack of a defined system in which the function of nuclear actin can be cleanly dissected biochemically and genetically. Taking advantages of the evolutionarily conserved actin- and Arp-containing INO80 chromatin remodeling complex and the yeast genetic system with a single actin gene, we have generated results showing that actin and Arps are stable and functional subunits of the INO80 complex. Our biochemical and genetic studies have established a defined system for the study of nuclear actin and Arps. Understanding the function and mechanism of the conserved actin and Arps in the nucleus has important implications in our basic understanding about chromatin and the cell nucleus.

PubMed 
 
 

Laboratory Webpage

Program Affiliation:

Program in Molecular Carcinogenesis

Contact Information

Phone: 512.237.9450

Email: xshen@mdanderson.org

Office: MDA SPR210, Lab III (Unit 116)

Title: Associate Professor

Education:

Ph.D. - University of Rochester - 1997