Dr. Lei Li
The University of Texas MD Anderson Cancer Center
Departments of Experimental Radiation Oncology and Genetics
Research projects in this laboratory are focused on molecular mechanisms of DNA damage repair and cell cycle checkpoint mechanisms, properly dubbed "care takers" and "gate keepers" for the maintenance of genome integrity. Defects in these mechanisms cause genomic instability -- a hallmark of cancer. Defective DNA repair or cell cycle checkpoint pathways allow DNA lesions to be converted to hereditary mutations during each round of cell division and allow these mutations to accumulate in proliferating cells. Ultimately, some cells, possessing effectual combinations of mutations, acquire tumorigenic competence and exhibit temporal-spatial dysregulation of cell growth characteristic of cancer cells.
We are interested in how DNA damage is sensed and transduced into checkpoint signals. We are investigating a number of genes that are critical in the generation of checkpoint signal and maintenance of genomic stability. By constructing genetic models both in animals and in somatic cells, we are able to elucidate their mechanism of function and their impact in tumorigenesis with particular interests in how checkpoint signals can be originated from DNA lesions and disrupted replication process. More recently, we have begin to explore how chromatin remodeling mechanisms interact with DNA repair and damage checkpoint pathways, since the highly compacted chromatin structure needs to be reconfigured to allowed access to DNA lesions. A second area of research deals with the repair of DNA interstrand cross-links, as many chemotherapy reagents are bifunctional DNA cross-linkers that covalently join the two strands of the double helix. We have identified a recombination-independent and error-prone pathway for the repair of DNA interstrand cross-links. Future studies will be focused on: 1. Characterization of the recombination-independent pathway of cross-link repair; 2. Identification of the essential components that carry out the error-free homologous recombination repair of interstrand DNA cross-links.
A tutorial in this laboratory will provide training in one or several of the following, molecular cloning, cell cycle analysis, cell biology techniques, homologous targeting in mammalian cells, recombinant protein production, and somatic gene silencing (siRNA). Candidates are also introduced into the field of DNA damage response mechanisms.