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Sonia Flores, PhD

Professor of Medicine


 



 

 

  Sonia Flores, PhD

  Professor of Medicine

  University of Colorado Denver

  Pulmonary Sciences & Critical Care Medicine

 

 

 Sonia.flores@ucdenver.edu

 

 

Education & Training

1979  BS, Biology, University of Puerto Rico, Mayagüez Campus, P.R.


1988  PhD, Biochemistry, University of South Alabama School of Medicine, Mobile, AL

1988 - 1989 Post-doctoral fellow, Microbiology/ Immunology, University of south Alabama School of
  Medicine, Mobile, AL

1989 - 1990  Fellowship, Biochemistry, University of South Alabama School of Medicine, Mobile, AL


Research Interests
 
1. We use 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.  We found that monkeys infected with SHIV-nef develop obliterative lesions in the pulmonary arteries.  These lesions are not seen in SIV-infected monkeys, suggesting that specific HIV nef alleles are essential for the vascular remodeling.  We infect monkeys with SHIV-nef chimeric viruses and track the biomarkers as the disease develops.  For these studies, we collaborate with the New England Primate Research Center.

2. Another project examines whether nef alleles isolated from HIV-infected patients with pulmonary hypertension have signature sequences associated with disease phenotype.  We are testing recombinant nef alleles in vitro for their ability to induce apoptosis of endothelial cells followed by selection of an apoptosis-resistant proliferative phenotype.   In addition, we are examining whether these alleles have an impact on viral fitness.

3. Another project examines the role of oxidant/antioxidant balance in the vascular complications in diabetes, particularly focusing on pathology of large blood vessels.  The non-obese diabetic mouse (NOD) develops diabetes spontaneously and is therefore a good model for Type I diabetes.  We have found that the blood vessels of this mouse are dysfunctional even in the pre-diabetic animal and that the immune dysfunction contributes to vascular complications.

Honors & Awards
1975                            General Excellence Scholarship, Italo-American Society, University of
                                    Puerto Rico
1975-79                       Dean's List of Academic Excellence
1977                            General Excellence Award; Highest G.P.A, University of Puerto Rico
1979                            Honorary Society of Phi Kappa Phi
1979                            Summa Cum Laude from the College of Arts and Sciences, University of Puerto Rico
 1986                           Procter and Gamble Graduate Fellowship administered by the American
                                    Society of Biological Chemists
1993                            New Investigator Award from the editors of Free Radical Biology &
                                    Medicine based on award winning abstract
1995                            Excellence in Education Award, Office of Diversity SEEK program,
                                    UCHSC
2005                            Department of Medicine Ph.D. Excellence in Research and
                                    Teaching Award
2006                            Excellence in Mentoring Award from Minority Student Organization
                                    Oyate
2008                            University of Colorado President’s Diversity Award
2010                            Recognized for service to peer review at NIH with the opportunity to submit certain grant applications at any time

Professional Experience

1991-96                       Assistant Professor, Department of Biochemistry, Biophysics and
                                    Genetics, UCHSC, Denver, Colorado
1993-94                       Director of Support Services, Center for Multicultural Enrichment, UCHSC,
                                    Denver, Colorado. 
1994-96                       Faculty Liaison for Center for Multicultural Enrichment
1996-97                       Assistant Professor, Department of Physiology, LSU Medical Center,
                                    Shreveport, LA
1997-2000                   Assistant Professor, Dept. Medicine, Webb-Waring Antioxidant Research
                                    Institute, UCHSC
2000-2004                   Associate Professor, Dept. Medicine and Biochemistry, UCHSC
2006-present               Associate Professor, Dept. of Medicine Pulmonary Division and
                                    Microbiology, UCHSC
2007-present               Professor, Dept. of Medicine and Microbiology, UCD Anschutz Medical Campus
2005-present               Program Director for the Graduate Experiences for Multicultural Students
                                                           (GEMS) program.  This NHLBI-funded R25 training program provides intense research experiences during the summer months for minority students interested in biomedical research.  
2008-present               Program Director, Initiative for Maximizing Student Diversity.  This NIGMS funded R25 is a pipeline training program designed to increase the diversity of students who matriculate at the University of Colorado Health


Publications

S.C. Flores, T.K. Moore, and J.W. Gaubatz. Dispersed repetitive sequences of mouse genome are differentially represented in extrachromosomal circular DNAs in vitro. Plasmid 17:257-260, 1987.


S.C. Flores, P.Sunnerhagen, T.K. Moore, and J.W. Gaubatz. Characterization of repetitive sequence families in mouse heart small polydisperse circular DNAs: Age related studies. Nucleic Acids Research 16: 3889-3906, 1988.


J.W. Gaubatz and S.C. Flores. Purification of eukaryotic extrachromosomal circular DNAs using exonuclease III. Analytical Biochemistry 184:305-310, 1990.


J.W. Gaubatz and S.C. Flores. Tissue-specific and age-related variations in repetitive sequences of mouse extrachromosomal circular DNAs. Mutation Research 237:29-36,1990.


B. Gao, S.C. Flores and J.M. McCord, A Site-Directed Mutant of Cu,Zn-Superoxide Dismutase Modeled After Native Extracellular Superoxide Dismutase, Biological Trace Element Research, 47:95-100, 1995.

 
S.C. Flores, J.C. Marecki, K.P. Harper, S.K. Bose, S.K. Nelson, and J.M. McCord, Tat protein of human immunodeficiency virus type 1 represses expression of manganese superoxide dismutase in HeLa Cells, Proc. Natl. Acad. Sci. USA, 90:7632-7636 (1993).


J.M. McCord, B. Gao, J. Leff, and Sonia C. Flores. Neutrophil-generated free radicals:possible mechanisms of injury in adult respiratory distress syndrome. Env. Health Perspectives 102:Suppl 11:57-60, 1994.
D.M. Guidot, J.E. Repine, A.D. Kitlowski, S.C. Flores, S.K. Nelson, R.M. Wright and J.M. McCord, Mitochondrial respiration scavenges extramitochondrial superoxide anion via a non-enzymatic mechanism:an additional role for electron transport. J. Clin Inv. 96:1131-1136, 1995.


B. Gao, S.C. Flores, and J.M. McCord, A novel Escherichia coli vector for oxygen-inducible high level expression of foreign genes. Gene, 176:269-272, 1996.


O. Prakash, S. Teng, M. Ali, X. Zhu, R. Coleman, R. Chambers, T.Y. Aw, S.C. Flores, and B.H. Joshi. HIV-1 Tat potentiates AZT-induced cellular toxicity in transgenic mice, Archives Biochemistry & Biophysics, 343: 173-180, 1997.
S.C. Flores and J.M. McCord, Redox regulation by the HIV-1 Tat transcriptional factor, In: Oxidative Stress and the Molecular Biology of Antioxidant Defenses, Cold Spring Harbor Laboratory Press, 117-138, 1997.
S. Komatsu, S.C. Flores, M.E. Gerritsen, D.C. Anderson, D.N. Granger. Differential up-regulation of circulating soluble and membrane-bound forms of murine intercellular adhesion molecule-1. American Journal of Pathology 151:205-14, 1997.


H. Ichikawa, S.C. Flores, P.R. Kvietys, R.E. Wolf, T. Yoshikawa, D.N. Granger, and T.K. Aw. Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Circulation Research, 81:922-931, 1997.


M. Seve, A. Favier, M. Osman, J.M. McCord, and S.C. Flores. The Tat protein from HIV-1 increases sensitivity to TPEN-induced apoptosis and changes Sp1 binding to DNA in HeLa cells. Archives of Biochemistry and Biophysics, 361:165-172, 1999.


G. M. Vaitaitis, R.J. Sanderson, E. J. Kimble, N.D. Elkins and S.C. Flores. Modification of enzyme-conjugated streptavidin-biotin Western blot technique to avoid detection of endogenous biotin-containing proteins. Biotechniques 26 (5):854?8, 1999


Y. Horie, R. Wolf, S.C. Flores, J.M.McCord, C.J. Epstein and D.N. Granger. Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion. Circ. Res. 83:691-696, 1998.


Faust-Chan R, Hybertson B, Flores SC, Wright RM, Repine JE Initiation and tolerance to acute lung injury: yin-yang mechanisms involving interleukin-1. Chest 116 (1 Suppl):102S?103S, 1999
Oshima, T, Flores, S.C., Vaitaitis, G., Coe, L, Joh, T., Park, J. H., Zhu, Y., Alexander, B. Alexander, J. S. Human immunodeficiency virus-1 Tat protein increases endothelial solute permeability through tyrosine kinase and MAP kinase-dependent pathways. AIDS 14: 1-8, 2000.


Tuder, RM, Wood, K, Taraseviciene, L, Flores, SC, Voelkel NF. Cigarette smoke extract decreases the expression of vascular endothelial growth factor by cultured cells and triggers apoptosis of pulmonary endothelial cells. Chest 117(5 Suppl 1):241S?2S, 2000.
Terada, L.S., Gu, Y., and Flores, S.C. AIDS Vasculopathy, The American Journal of Medical Sciences, 200: 379-387, 2000


Richard, M-J, Guiraud, P., Didier, C., Seve, M, Flores, S.C. and Favier, A. Human immunodeficiency virus-1 Tat protein impairs selenoglutathione peroxidase expression and activity by a mechanism independent of cellular selenium uptake: consequences on cellular resistance to UV-A radiation. Arch. Biochem. Biophys. 386:213-220, 2001
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.


Kasahara, Y., Tuder, RM., Cool, CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med, 163(3 Pt 1):737?44, 2001.


Piganelli, J.D*., Flores, S.C.*, Cruz, C., Koepp, J., Batinic-Haberle, I., Kachadourian, R., Young, R., Bradley, B., and Haskins, K. A metalloporphyrin-based Superoxide Dismutase mimic Inhibits Autoimmune Diabetes, In Press, Diabetes. (*Both authors contributed equally).


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. Under revision, J. Biol. Chemistry, 2001