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Genomic Instability and Cancer Genetics Research Program

Program Leaders: Zhiyuan Shen, MD, PhDChang S. Chan, PhD, and Cristina Montagna, PhD

Overall Goals:

To determine how cells maintain the integrity of their genomes, to define the landscapes of cancer genomes, and to facilitate the identification of biomarkers and therapeutic targets. The research and collaboration activities are organized around the central concepts that cancer results from the accumulation of genomic alterations, and that well-defined descriptions of DNA repair mechanisms, cancer genomes, and gene expression landscapes can reveal the vulnerability of cancer to interventions.

Specific Aims:

  • To elucidate mechanisms of genome maintenance through the study of cell and molecular biology, genetics, biochemistry, structural biology, and by using small animal and other model organisms. The goals are to elucidate the core mechanisms that provoke genomic instability, including imprecise repair of DNA damage, DNA replication infidelity, and chromosome segregation errors, and how they lead to cancer and treatment susceptibility. 
  • To understand the regulatory networks that coordinate tumorigenesis-modulating pathways with genome maintenance using cell and molecular biology approaches. The goals are to understand how gene expression regulation and signal transduction networks respond to intrinsic cellular homeostasis and environment changes and interface with DNA repair and genome maintenance machineries to modulate tumorigenesis. 
  • To define the altered genome landscape and unique gene expression signatures in cancer using computational and experimental genomic approaches. The goals are to identify: 1) clinically relevant tumor sub-types based on molecular profiling; 2) the process of tumor clonal evolution, heterogeneity and the associated driver mutations; 3) cancer-relevant non-coding variants and coding variants of unknown significance; and 4) the underlying mechanism of genomic instability based on the profiling of global genome changes in cancer. 

Collaborating Research Programs:

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