Pedro O. Flores Villanueva, M.D., M.S., M.M.S.
Intern in Medicine, Edgardo Rebagliati Hospital, Lima, Peru
After completing his post-doctoral training at Harvard, Dr. Flores-Villanueva was appointed Instructor of Pathology at Harvard Medical School. He served then as Assistant Professor and later as Associate Professor in Immunology at the University of Texas Health Science Center at Tyler in 2005 and early 2007, respectively. He joined Houston Methodist Research Institute in 2007 in the Center for Molecular Translational Human Infectious Disease Research.
Dr. Flores-Villanueva has received numerous honors and awards in his career to date including the Latin America Academy of Science (Caracas, Venezuela) Post-Graduate Award, a UNESCO Scholarship (International Cell Research Organization), a Research National Council Scholarship (Sao Paulo, Brazil), and a Bridge Award for Outstanding Minority Faculties from Harvard Medical School.
Our research is “translational” in nature. Our goal is to identify genetic determinants controlling the expression of susceptibility to microbial pathogens in populations of different ethnicity, living in diverse environments, and practicing diverse lifestyles. The identification of gene variants responsible for the expression of such complex traits will lead us to the characterization of “defects” in pathways, and then will allow the formulation of new population-based clinical interventions, including better vaccines.
My laboratory has already identified a polymorphism associated with increased susceptibility to developing active pulmonary Tuberculosis: the -2518 MCP-1 functional promoter polymorphism (J Exp Med, 2005). As this is a complex trait and this polymorphism is present in about 30% of the affected individuals of Mexican and Korean ancestry, it is likely that other gene variants will be also involved, alone or in interaction with MCP-1, in the expression of disease. Thus, with support from the NIH we are conducting large case-control studies in Peru and Mexico, countries with high and low to moderate TB-case burden, respectively. With additional support from TMHRI, we have developed an SNP microarray assay, using a flexible Illumina platform, to test multiple potentially functional polymorphisms in disease susceptibility and in studies of vaccine efficacy in populations of diverse ethnicity. This array comprises SNPs located in promoter and coding regions of genes of the immune and inflammatory systems.
For the identification of “defects” in cellular and molecular pathways, we are using state-of-the-art integrative experimental and analytical approaches. We are gathering valuable information from ex vivo and in vitro experiments that we conduct using cells, tissue, plasma, and RNA samples obtained from already genotyped cases and controls. The identification of genes and pathways affected will finally support the development of more rational animal models of human disease that we will use to establish proof-of-concept when testing new clinical interventions.
Tuberculosis, population genetics, immunogenetics, translational medicine
Principal Investigator: Pedro O. Flores-Villanueva, M.D., M.S., M.M.S.
Title: MCP-1and MMP-1 contributions in susceptibility to developing active tuberculosis.
Feng WX, Flores-Villanueva PO, Mokrousov I, Wu XR, Xiao J, Jiao WW, Sun L, Miao Q, Shen C, Shen D, Liu F, Jia ZW, Shen A. CCL2-2518 (A/G) polymorphisms and tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2012 Feb;16(2):150-6.
Ganachari M, Ruiz-Morales JA, Gomez de la Torre Pretell JC, Dinh J, Granados J, Flores-Villanueva PO. Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals. PLoS One. 2010 Jan 25;5(1):e8881.
Flores-Villanueva PO, Ruiz-Morales JA, Song CH, Flores LM, Jo EK, Montaño M, Barnes PF, Selman M, Granados J. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J Exp Med. 2005 Dec 19;202(12):1649-58.