Luis A. Martinez, PhD, Associate Professor

Luis A. Martinez, PhD 
Associate Professor
Department of Pathology
Basic Sciences Tower
Stony Brook Medicine
Stony Brook, NY 11794-8691

Tel: 631-444-3000
Fax: 631-444-3424
Email: Luis.Martinez@stonybrookmedicine.edu

Research Interests: Dr. Martinez’s research is focused on understanding how alterations in the p53 gene contribute to the development of cancer. The wildtype form of p53 is a critical tumor suppressor gene that is frequently inactivated in human cancers. The majority of genetic lesions suffered by this tumor suppressor gene are missense mutations that disable its ability to block tumor development. However, these missense mutations can also give rise to mutant forms of p53 (mutant p53) that function as oncogenes that promote cancer progression through what is collectively referred to as gain-of-function (GOF) activities. One of the primary areas of investigation in Dr. Martinez’s laboratory has been to determine the underlying mechanism(s) that permit mutant p53 to exhibit GOF activity. His laboratory discovered that mutant p53 is recruited to approximately 50% of its transcriptional targets through an interaction with the ETS2 transcription factor. Additionally, the work from Dr. Martinez’s laboratory implicated the mutant p53/ETS2 complex as a common mechanism by which different mutant p53 proteins are able to regulate the same spectrum of transcriptional targets. This fundamental mechanism has since been validated by other laboratories and appears to be the predominant mechanism by which mutant p53 controls the expression of any genes that mediate its oncogenic activity. We have also established that mutant p53 can stabilize the ETS2 protein (and not other ETS family members), by disrupting its ubiquitin-mediated degradation. The stabilization of ETS2 by mutant p53 thus serves to amplify mutant p53’s ability to regulate gene expression by increasing the abundance of mutant p53/ETS2 complexes. Future studies are aimed at further dissecting how this transcriptional target regulates gene expression and how the interaction of mutant p53 with other proteins contributes to tumor progression.

Education:

Positions and Employment:

Selected Publications:

Yun J, Espinoza I, Pannuti A, Romero D, Martinez L, Caskey M, Stanculescu A, Bocchetta M, Rizzo P, Band V, Band H, Kim HM, Park SK, Kang KW, Avantaggiati ML, Gomez CR, Golde T, Osborne B, Miele L. p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1. J Cell Physiol. 2015 Dec;230(12):3115-27

Kollareddy M, Dimitrova E, Vallabhaneni KC, Chan A, Le T, Chauhan KM, Carrero ZI, Ramakrishnan G, Watabe K, Haupt Y, Haupt S, Pochampally R, Boss GR, Romero DG, Radu CG, Martinez LA*. Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities. Nat Commun. 2015 Jun 12; *corresponding author

Xing F, Sharma S, Liu Y, Mo YY, Wu K, Zhang YY, Pochampally R, Martinez LA, Lo HW, Watabe K. miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-α. Oncogene. 2015 Sep 10;34(37):4890-900.

Xiong S, Tu H, Kollareddy M, Pant V, Li Q, Zhang Y, Jackson JG, Suh YA, Elizondo-Fraire AC, Yang P, Chau G, Tashakori M, Wasylishen AR, Ju Z, Solomon H,Rotter V, Liu B, El-Naggar AK, Donehower LA, Martinez LA, Lozano G. Pla2g16 phospholipase mediates gain-of-function activities of mutant p53. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11145-50.

Subramanian M, Francis P, Bilke S, Li XL, Hara T, Lu X, Jones MF, Walker RL, Zhu Y, Pineda M, Lee C, Varanasi L, Yang Y, Martinez LA, Luo J, Ambs S, Sharma S, Wakefield LM, Meltzer PS, Lal A. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis. Oncogene. 2015 Feb 26;34(9):1094-104.

Do PM, Varanasi L, Fan S, Li C, Kubacka I, Newman V, Chauhan K, Daniels SR,Boccetta M, Garrett MR, Li R, Martinez LA*. Mutant p53 cooperates with ETS2 to promote etoposide resistance. Genes Dev. 2012 Apr 15;26(8):830-45; *corresponding author 

Varanasi L, Do PM, Goluszko E, Martinez LA*. Rad18 is a transcriptional target of E2F3. Cell Cycle. 2012 Mar 15;11(6):1131-41. *corresponding author

Gilder AS, Do PM, Carrero ZI, Cosman AM, Broome HJ, Velma V, Martinez LA, Hebert MD. 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. *Co-corresponding author

Martinez LA*, Goluszko E, Chen HZ, Leone G, Post S, Lozano G, Chen Z, Chauchereau A. E2F3 is a mediator of DNA damage-induced apoptosis. Mol Cell Biol. 2010 Jan;30(2):524-36. *corresponding author