Jorge L. Sepulveda, MD
Associate Professor of Clinical Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Contact information
Interim Chief & Director of Clinical Pathology
Pathology and Laboratory Service, 113
Philadelphia VAMC
University and Woodland Avenues
Philadelphia, PA 19104
Pathology and Laboratory Service, 113
Philadelphia VAMC
University and Woodland Avenues
Philadelphia, PA 19104
Office: 215-823-4421
Fax: 215-823-4271
Fax: 215-823-4271
Email:
jorge.sepulveda@va.gov
jorge.sepulveda@va.gov
Publications
Education:
MD
University of Lisbon, 1984.
Ph.D.
Baylor College of Medicine, 1995.
Permanent linkMD
University of Lisbon, 1984.
Ph.D.
Baylor College of Medicine, 1995.
Description of CVI Expertise
CVI Program Unit(s):Cardiovascular Development / Congenital Heart Disease
Lipid / Atherosclerosis / CAD / ACS / Prevention
Myocyte Biology / Heart Failure
CVI Research Description:
The main projects in Dr. Sepulveda's laboratory are centered on the investigation of molecular mechanisms of cellular development and differentiation. More specifically, we are interested in transcriptional regulation of cardiac myocyte phenotypes during cardiogenesis and during the development of heart failure. Our work has focused on three transcriptional regulators that are highly expressed during cardiogenesis and subsequently in the adult myocardium: serum response factor (SRF), the homeobox gene Nkx2-5 and the zinc finger protein GATA-4.
We have discovered that interactions between these factors drive high levels of transcription of cardiac-specific genes such as alpha-cardiac-actin. We are currently interested on integrin signaling and its effects on cardiac myocyte transcriptional regulation. In particular, we have focused our efforts on hypertrophic signaling involving fibronectin induction of integrin receptors and integrin-linked kinase (ILK), both in neonatal and adult cardiac myocytes. We created a mouse model of apoptotic cardiomyopathy by conditional deletion of the ILK gene in the heart, highlighting the importance of this protein in cardiac myocyte survival.
Recently, we discovered a connection between hypertrophic stimuli and regulation of lipid synthesis by SREBP transcription factors. Our laboratory uses a comprehensive molecular biology, genomics and proteomics approach to elucidate these questions in cardiac myocyte development and dysfunction. In the clinical laboratory field, we use mass-spectrometry techniques to identify markers of cardiovascular disease, with our current focus on fatty acid analysis.
Selected Publications
Sepulveda, JL, Tanhehco, YC, Frey, M, Guo, L, Cropcho, LJ, Gibson, KM, Blair, HC.: Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids: Correlation with Cardiovascular Disease. Archives of Pathology and Laboratory Medicine In Press, 2009.Tanhehco YC, Peck Palmer OM, Derrico LS, Sepulveda JL, Blair HC.: Biases in antibody-based single-phase assays for free thyroxine due to protein-bound analyte. Clin Chim Acta 406(1-2): 176-8, 2009.
O’Keefe, SJ, Ou, J, Aufreiter, S, O’Connor, D, Sharma, S, Sepulveda, JL Fukuwatari, T, Shibata, K, Mawhinney, T: The Nutritional Role of the Microbiota in Populations with a High and Low Risk of Colon Cancer. Journal of Nutrition (Accepted for publication, May 2009) 2009.
Lee, W. C., Sepulveda, J. L., Rubin, J. P., Marra, K. G.: Cardiomyogenic differentiation potential of human adipose precursor cells. Int J Cardiol 133(3): 399-401, 2009.
Yao, Y., Tao, H., Park, D. I., Sepulveda, J. L., Sepulveda, A. R.: Demonstration and characterization of mutations induced by Helicobacter pylori organisms in gastric epithelial cells. Helicobacter 11(4): 272-86, 2006.
Chen, H., Huang, X. N., Yan, W., Chen, K., Guo, L., Tummalapali, L., Dedhar, S., St-Arnaud, R., Wu, C., Sepulveda, J. L.: Role of the integrin-linked kinase/PINCH1/alpha-parvin complex in cardiac myocyte hypertrophy. Lab Invest 85(11): 1342-56, 2005.
Chikwava, K., Lower, D. R., Frangiskakis, S. H., Sepulveda, J. L., Virji, M. A., Rao, K. N.: Acute ethanol intoxication in a 7-month-old infant. Pediatr Dev Pathol 7(4): 400-2, 2004.
Chen, H., Huang, X. N., Stewart, A. F., Sepulveda, J. L.: Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy. Physiol Genomics 18(3): 273-83, 2004.
Sepulveda, J. L., Vlahopoulos, S., Iyer, D., Belaguli, N., Schwartz, R. J.: Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity. J Biol Chem 277(28): 25775-82, 2002.
Sepulveda, A. R., Tao, H., Carloni, E., Sepulveda, J., Graham, D. Y., Peterson, L. E.: Screening of gene expression profiles in gastric epithelial cells induced by Helicobacter pylori using microarray analysis. Aliment Pharmacol Ther 16 Suppl 2: 145-57, 2002.