Dr. Elsa R. Flores
The University of Texas MD Anderson Cancer Center
Department of Biochemistry and Molecular Biology
- Tumor suppressor genes
- DNA damage
- Stem cells
- Transcriptional regulation
- Mouse genetics
In the post-genomic era, many gene families have been identified. These genes can have overlapping and independent functions. The existence of redundant functions in gene families has made diseases like cancer challenging to treat and cure. The focus of my laboratory is to understand the intricacy of the p53 family of genes in cancer using mouse genetics and biochemical approaches. The goal of our work is to gain a global understanding of the complex functions of this gene family in cancer and to facilitate the design of targeted therapies for cancer patients with alterations in this family of genes. This type of research can be applied to other families of genes with redundant and unique functions in an effort to make significant progress in curing diseases like cancer.
Given the structural and functional similarity of p63 and p73 to p53, the early assumption was that these new family members were also tumor suppressor genes. The functions of p63 and p73 are not that simple due to the existence of isoforms with opposing functions including transactivation competent (TA) isoforms and those lacking the transactivation domain (ΔN). To determine the functions of these isoforms, my laboratory has generated conditional knock out mouse models that allow the deletion of the TA or ΔN isoforms of p63 or p73. Using these mouse models, we have unveiled previously unrecognized functions of p63 and p73 in the maintenance of adult skin stem cells and DNA repair. Current experiments using these novel mouse models are aimed at understanding the transcriptional network regulated by the isoforms of p63 and p73 in stem cell maintenance, DNA damage responses, tumor suppression, and metastasis.
A tutorial in my laboratory would include using these new mouse models to understand the p53 family of genes in multiple biological processes. The student will gain experience in mouse genetics and anatomy, stem cell and tissue culture, and transcriptional assays.