Joshua Lewis completed his undergraduate training at the State University of New York College of Environmental Science and Forestry in conjunction with Syracuse University receiving a bachelor's degree in biotechnology. He then completed his Ph.D. in Molecular Genetics and Genomics at the Center of Human Genomics and Personalized Medicine at Wake Forest University School of Medicine. Dr. Lewis completed his postdoctoral fellowship at the University of Maryland School of Medicine in the Division of Endocrinology, Diabetes, and Nutrition and in the Program in Personalized and Genomic Medicine. He was recruited to the Department of Medicine at the University of Maryland in 2012.
Cardiovascular disease is currently the leading causes of death in the United States. The goal of Dr. Lewis' research is to identify and functionally characterize genes contributing to cardiovascular disease in order to ultimately translate genetic discoveries into individualized patient care through pharmacogenomics and/or other clinical approaches.
Aspirin and clopidogrel therapy significantly improves cardiovascular outcomes in patients with various coronary syndromes by inhibiting platelet function. However, variable inter-individual responses to anti-platelet therapies exist resulting in increased risk of recurrent cardiovascular events in some patients. Dr. Lewis' objective is to identify genetic variants through candidate gene studies, genome-wide association analyses, and other "omics" approaches that contribute to differences in platelet response and to functionally elucidate the molecular mechanisms responsible for this variability. Studies by Dr. Lewis have shown that genetic variants in the Platelet Endothelial Aggregation Receptor 1 (PEAR1) gene are associated with platelet reactivity and cardiovascular outcomes in patients on aspirin therapy. He is currently exploring further the functional consequences of these polymorphisms in cellular models as well as in human populations. In addition, potential pharmacogenetic effects of paraoxonase 1 (PON1), carboxyesterase 1 (CES1), and ATP-binding cassette sub-family C member 4 (ABCC4) on clopidogrel efficacy are currently being investigated.
Lewis JP, O'Connell JR, Ryan K, Horenstein RB, Damcott CM, Gibson Q, Pollin TI, Mitchell BD, Beitelshees A, Pakzy R, Parsa A, Tantry US, Bliden KP, Post W, Faraday N, Gong Y, Pepine C, Herzog W, Johnson J, Gurbel PA, Shuldiner AR. Association of Polymorphisms in PEAR1 with Platelet Aggregation and Cardiovascular Outcomes in Patients on Aspirin Therapy. [Submitted to Circ Cardiovasc Genet]
Lewis JP, Horenstein RB, Ryan K, O'Connell JR, Gibson Q, Mitchell BD, Tanner K, Chai S, Bliden KP, Tantry US, Peer CJ, Figg WD, Spencer SD, Pacanowski MA, Gurbel PA, Shuldiner AR. The Functional G143E Variant of Carboxylesterase 1 is Associated with Increased Clopidogrel Active Metabolite Levels and Greater Clopidogrel Response. Pharmacogenet Genomics 2012 Oct [Epub ahead of print]
Reny JL, Combescure C, Daali Y, Fontana P, Aradi D, Delaney J, Dery JP, Gurbel PA, Lewis JP, Sibbing D, Taubert D, Trenk D, Ancrenaz V, Desmeules J, Perrier A, Poncet A, Sanchez JC, Zuffrey A.. Influence of the Paraoxonase-1 Q192R Genetic Variant on Clopidogrel Responsiveness and Recurrent Cardiovascular Events: A Systematic Review and Meta-Analysis. J Thromb Haemost. 2012 Jul; 10(7): 1242-1251
Lewis JP and Shuldiner AR. PON1 Q912R Variant and Clopidogrel Efficacy: Fact or Fiction? Circ Cardiovasc Genet. 2012 Apr; 5(2): 153-155
Allred ND, McDonough CW, Bostrom MA, Hicks PJ, Roh BH, Wing MR, Hester JM, An SS, Talbert ME, Lewis JP, Rudock ME, Cooke JN, Rudock, ME, Lu L, Ng MCY, Sale MM, Divers J, Langefeld CD, Ziegler J, Shriner D, Rotimi C, Ferrara A, Freedman BI, Bowden DW. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans. PLoS One. 2012 Jan; 7(1):e29202
Lewis JP, Fisch AS, O'Connell JR, Ryan K, Horenstein RB, Gibson Q, Mitchell BD, Pakzy R, Shen H, Tanner K, Tantry US, Bliden KP , Gurbel PA, Shuldiner AR. Paraoxnase 1 (PON1) Gene Variants are Not Associated with Clopidogrel Response. Clin Pharmacol Ther. 2011 Oct; 90(4):568-74
Johnson JA, Cavallari LM, Beitelshees AL, Lewis JP, Shuldiner AR, Roden DM. Pharmacogenomics: Application to the Management of Cardiovascular Disease. Clin Pharmacol Ther. 2011 Oct; 90(4):519-31
McDonough CW, Palmer ND, Bostrom MA, Hicks PJ, Roh BH, Wing MR, Cooke JN, Hester JM, An SS, Talbert ME, Lewis JP, Rudock ME, Lu L, Ng MCY, Sale MM, Divers J, Langefeld CD, Freedman BI, Bowden DW. A Genome-Wide Association Study for Diabetic Nephropathy Genes in African Americans. Kidney Int. 2011 Mar; 79(5):563-72
Lewis JP, Shuldiner AR. Genetics of the Metabolic Complications of Obesity (2010) In: Genetics of Adipose Tissue and Obesity. Bouchard C, (ed), Progress in Molecular Biology and Translational Science, Academic Press., pp 349-372
Lewis JP, Palmer ND, Ellington JB, Langefeld CD, Freedman BI, Bowden DB. Analysis of Candidate Genes on Chromosome 20q12-13.1 Reveals Evidence for BMI Mediated Association of PREX1 with Type 2 Diabetes in European Americans. Genomics. 2010 Oct; 96(4):211-9
Lewis JP, Palmer ND, Hicks PJ, Sale MM, Langefeld CD, Freedman BI, Bowden DW. Association Analysis in African Americans of European-Derived Type 2 Diabetes Single Nucleotide Polymorphisms from Whole-Genome Association Studies. Diabetes. 2008 Aug; 57(8): 2220-5
Bento JL, Palmer ND, Zhong M, Roh B, Lewis JP, Wing MR, Pandya H Freedman BI, Rich SS, Langefeld CD, Bowden DW, Mychaleckyj JC. Heterogeneity in Gene Loci Associated with Type 2 Diabetes on Human Chromosome 20q13.1. Genomics. 2008 Oct; 92(4): 226-34
Lehtinen AB, Burdon KP, Lewis JP, Langefeld CD, Ziegler JT, Rich SS, Register TC, Carr JJ, Freedman BI, Bowden DW. Association of Alpha2-Heremans-Schmid Glycoprotein with Subclinical Atherosclerosis. J Clin Endocrinol Metab. 2006 Jan; 92(1): 345-52