Luis A. Martinez
Associate Professor
Tumor Cell Biology Program
Ph.D., Biological Sciences, 1998, University of Texas at Austin
Postdoc, 1998-2001, UT MD Anderson, USA
Postdoc, 2001-2004, Institut Andre Lwoff, France
Contact Information
2500 N State St, Room G220
Jackson, MS 39216
Phone: 601-984-1521
Email: lmartinez@umc.edu
Research Interests
- Mutant p53 oncogenic functions
- E2F proteins
- Transcriptional response to DNA damage
Research Synopsis
Resistance to DNA damaging chemotherapeutic agents represents a major hurdle for the successful treatment of cancer. My lab is focused on understanding the role of two transcription factors, mutant p53 and E2F3, in the cellular response to DNA damage. p53 is the most frequently mutated tumor suppressor gene in human cancer. The vast majority of p53 mutations are a single base pair change that generally produces a mutant protein incapable of transactivating wildtype p53 target genes. However, substantial evidence indicates that mutant p53 has gain-of-function activity that is dependent on its de novo ability to regulate gene expression. We have previously demonstrated that suppression of mutant p53 expression can lead to cell death. We are presently investigating mutant p53's transcriptional regulatory activity and assessing the significance of this function in the promotion of chemotherapy resistance. The second major project revolves around the pro-apoptotic role of the E2F transcription factor family in the response to DNA damage. We have demonstrated that E2F3a can be induced by genotoxic stress and that in its absence, DNA damage induced apoptosis is severely compromised. We are presently investigating how E2F3 contributes to the response to DNA damage by identifying its transcriptional targets, and we are also assessing if changes in E2F3 activity contribute to chemotherapy resistance in cancer cells.
Recent Accomplishments and Honors
2001 Chateaubriand Fellowship
2002 Association pour la Recherche sur le Cancer Fellowship
2003 Fondation Medicale Recherche Fellowship
Selected Publications
- Gilder AS et al. Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage. Mol Biol Cell. 2011 Apr;22(7):1070-9.
- Martinez LA, et. al. E2F3 is a Mediator of DNA Damage Induced Apoptosis. Mol Cell Biol. 2010 Jan;30(2):524-36
- Chen Z, et. al. Stabilization of p53 in human cytomegalovirus-initiated cells is associated with sequestration of HDM2 and decreased p53 ubiquitination. J Biol Chem. 2007 Oct 5;282(40):29284-95
- Tchenio, T., et. al. Heat shock-independent induction of multidrug resistance by heat shock factor 1. Mol Cell Biol. 26(2):580-91. Jan 2006
- Martinez, LA, et. al. Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci USA. 99(23):14849-54. Nov 12, 2002.
