Sonia Flores
Associate Professor Ph.D., University of South Alabama, Mobile
Current Research
Dr. Flores laboratory investigates the role of the cellular redox status on host defenses. The first project analyzes the effects of the HIV-1 transcriptional regulator Tat on the redox status of host cells and the consequences of such effects. The HIV-1 transcriptional regulator Tat is secreted from infected cells and taken up by uninfected cells. One of its downstream effects is to alter the cellular redox status by, among others, down-regulation of the human antioxidant enzyme Mn-superoxide dismutase (Mn-SOD). She is investigating whether redox status alterations in a transgenic mouse with lung-specific Tat expression has altered susceptibility to pulmonary pathogens including Mycobacterium tuberculosis or avium.
The second project in Dr. Flores' laboratory seeks to examine the mechanisms of one of the cardiopulmonary complications in AIDS: the presence of inflammatory infiltrates in the absence of any common pathogen. She is testing whether soluble Tat changes innate immune responses to pathogens in vitro and in vivo.
The third project in Dr. Flores’ laboratory uses a model of chimeric SIV-HIV-nef (SHIV-nef) infection of Rhesus macaques to study pulmonary hypertension and vascular remodeling in the context of HIV infection. This laboratory has found that monkeys infected with SHIV-nef develop obliterative lesions in the pulmonary arteries that result in increased mean arterial pulmonary pressure and increased right ventricular hypertrophy. These lesions are not seen in SIV-infected monkeys, suggesting that specific HIV nef alleles are essential for the vascular remodeling. Monkeys are infected with SHIV-nef chimeric viruses and biomarkers associated with disease development are tracked. In vitro, cultured human endothelial cells are exposed to nef alleles as well as domain mutants to determine whether Nef affects cellular phenotypic and molecular characteristics.
The fourth project in Dr. Flores’ laboratory examines the evolution of HIV nef sequences in peripheral blood mononuclear cells, plasma, and bronchoalveolar lavage fluid in longitudinal samples from HIV-infected patients with pulmonary hypertension. Signature sequences associated with disease are then tested for their transformation and angioproliferative potential in cultured human endothelial cells.
Recent Publications
Click Here For An Updated List Of Dr. Flores' Publications
Gu, Y., Wu,F.R., Xu, C.Y., Flores, S.C. and Terada, L.S. HIV Tat activates c-Jun Terminal kinase Through an Oxidant-Dependent Mechanism. Virology Jul 20;286(1):62 71, 2001.
Cota-Gomez, A. Flores, N.C., Cruz, C., Casullo, A., Aw,T.Y., Ichikawa, H, Schaack, J., Scheinman, R., and Flores, S.C. The human immunodeficiency virus-1 Tat protein activates human umbilical vein endothelial cell E-selectin expression via an NF-kB-dependent mechanism. J. Biol. Chemistry, 277:14390-14399, 2002
J.C. Marecki, A. Cota-Gomez, G. M. Vaitaitis, J.R. Honda, S. Porntadavity, D.K. St. Clair, and S.C. Flores. HIV-1 Tat regulates the SOD2 basal promoter by altering Sp1/Sp3 binding activity. Free Radicals in Biology and Medicine, 37 (6): 869-880, 2004.
Porntadavity S, Nath A, Prachayasittikul V, Cota-Gomez A, Flores SC, St Clair DK. Different roles of Sp family members in HIV-1 Tat-mediated manganese superoxide dismutase suppression in hepatocellular carcinoma cells. DNA Cell Biol. 24:299-310, 2005.
Connor KM, Subbaram S, Regan KJ, Nelson KK, Mazurkiewicz JE, Bartholomew PJ, Aplin AE, Tai YT, Aguirre-Ghiso J, Flores SC, Melendez JA. Mitochondrial H2O2 regulates the angiogenic phenotype Via PTEN oxidation.
J Biol Chem. 280:16916-24, 2005.
Marecki, J. Cool, C., Voelkel, N., Luciw, P. and Flores, S.C. Evidence for vascular remodeling in the lungs of macaques infected with simian immunodeficiency virus/HIV NEF recombinant virus. Chest. 128(6 Suppl):621S-622S, 2005.
Marecki, J.C., Cool, C., Parr, J.E., Beckey, V.E., Luciw, P.A., Tarantal, A.F., Carville, A., Shannon, R.P., Cota-Gomez, A., Tuder, R.M., Voelkel, N.F., and Flores, S.C. HIV-1 Nef is associated with angioproliferative pulmonary arterial disease in SHIV-nef-infected macaques, Amer.J.Resp.Critical Care Med. 174:437-445, 2006
Tuder, R.M., Marecki, J.C. Richter, A, Fijalkowska, I., Flores, S.C., Pathology of Pulmonary Hypertension, Clinics in Chest Medicine, 28(1):23-42, 2007.
Petrache, I.,Stephens, R.S., Diab,K., Knox, K.S., Twigg, H.L., Flores, S.C., and Tuder, R.M., HIV- associated pulmonary emphysema. A review of the literature and inquiry into its mechanism, Thorax, in press.
