Health Science Facility III, Rm. 4171
Education and Training
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.
Antiplatelet therapy significantly improves cardiovascular outcomes in patients with various coronary syndromes by inhibiting platelet function. However, variable inter-individual responses to such 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, next-generation sequencing, and other "omics" approaches that contribute to differences in platelet response and cardiovascular disease risk in order 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. Dr. Lewis is a member of multiple professional societies and genomics-based consortia including the Pharmacogenomics Research Network (PGRN), Clinical Pharmacogenomics Implementation Consortium (CPIC), and Trans-Omics for Precision Medicine (TOPMed) Program in order to identify novel genetic variation that lead to disease susceptibility and altered drug response.
Complex Disease Genetics, Pharmacogenomics, Personalized Medicine, Cardiovascular Disease
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 and Genomics. 2013 Jan; 23(1):1-8
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. Genetic Variation in PEAR1 is Associated with Platelet Aggregation and Cardiovascular Outcomes. Circ Cardiovasc Genet. 2013 Apr; 6(2):184-192
Lewis JP, Stephens SH, Horenstein RB, O’Connell JR, Ryan K, Peer CJ, Figg WD, Spencer SD, Pacanowski MA, Mitchell BD, and Shuldiner AR. The CYP2C19*17 Variant is not Independently Associated with Clopidogrel Response. J. Thromb. Haemost. 2013 Sep; 11(9): 1640-1646
Lewis JP, Yerges-Armstrong LM, Ellero-Simatos S, Georgiades A, Kaddurah-Daouk R, and Hankemeier T. Integration of Pharmacometabolomic and Pharmacogenomic Approaches Reveal Novel Insights into Antiplatelet Therapy. Clin Pharmacol Ther. 2013 Nov; 94(5):570-573
Fisch AS, Yerges-Armstrong LM, Donnelly, P, Ryan KA, Parihar A, Mitchell BD, O’Connell JR, Herzog W, Wren JD, Lewis JP. Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 (PEAR1) Gene is Associated with Endothelial Dysfunction. PLoS One. 2015 Sep 25;10(9):e0138795.
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
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
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
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
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, 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
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
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
Yerges-Armstrong LM, Ellero-Simatos S, Georgiades A, Zhu H, Lewis JP, Horenstein RB, Beitleshees AL, Dane A, Reijmers T, Hankemeier T, Fiehn O, Shuldiner AR, Kaddurah-Daouk R. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics. Clin Pharmacol Ther. 2013 Oct; 94(4): 525-532
Ellero-Simatos S, Lewis JP, Georgiades A, Yerges-Armstrong L, Beitelshees AL, Horenstein RB, Dane A, Harms A, Ramaker R, Perry CG, Zhu H, Shuldiner AR, Hankemeier T, Kaddurah-Daouk R. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability. CPT Pharmacometrics Syst. Pharmacol. 2014 Jul 16;3:e125. doi: 10.1038/psp.2014.22.
Beitelshees AL, Voora D, and Lewis JP. Personalized Anti-Platelet and Anti-Coagulation Therapy – Applications and Significance of Pharmacogenomics. Pharmgenomics Pers Med. Feb 2015; (8): 43-61
McDonough CW, McClure LA, Mitchell BD, Gong Y, Horenstein RB, Lewis JP, Field TS, Talbert RL, Benavente OR, Johnson JA, Shuldiner AR. CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study. J Am Heart Assoc. 2015 May 27;4(6)
Bozzi LM, Mitchell BD, Lewis JP, Ryan KA, Herzog W, O’Connell JR, Horenstein RB, Shuldiner AR, Yerges-Armstrong LM. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Platelet Response to Clopidogrel and Aspirin. Curr Vasc Pharmacol. 2016;14(1):116-24
Yang Y, Lewis JP, Hulot JS, and Scott SA, The Pharmacogenetic Control of Antiplatelet Response: Candidate Genes and CYP2C19. Expert Opin Drug Metab Toxicol. 2015 Oct;11(10):1599-617
Ellero-Simatos S*, Beitelshees AL*, Lewis JP*, Yerges-Armstrong LM, Georgiades A, Dane A, Harms AC, Strassburg K, Guled F, Hendriks M, Horenstein RB, Shuldiner AR, Hankemeier T, Kaddurah-Daouk R, and the Pharmacometabolomics Research Network. Oxylipid Profile of Low-Dose Aspirin Exposure – A Pharmacometabolomic Study. J Am Heart Assoc. 2015 Oct 26;4(10):e002203.*Authors contributed equally
Jiang XL, Samant S, Lewis JP, Horenstein RB, Shuldiner AR, Yerges-Armstrong LM, Peletier LA, Lesko LJ, and Schmidt S. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults. Eur J Pharm Sci.2015 Oct 30; (82):64-78.
Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu CT, Hong J, Jensen RA, Rice K, Morris AP, Mägi R, Tönjes A, Prokopenko I, Kleber ME, Delgado G, Silbernagel G14, Jackson AU, Appel EV, Grarup N, Lewis JP, Montasser ME, Landenvall C, Staiger H, Luan J, Frayling TM, Weedon MN, Xie W, Morcillo S, Martínez-Larrad MT, Biggs ML, Ida Chen YD, Corbaton-Anchuelo A, Færch K, Zumaquero JM, Goodarzi MO, Kizer J, Koistinen HA30, Leong A, Lind L, Lindgren C, Machicao F, Manning AK, Martín-Núñez GM, Rojo-Martínez G, Rotter JI, Siscovick DS, Zmuda JM, Zhang Z, Serrano-Rios M, Smith U, Soriguer F, Hansen T, Jørgensen TJ, Linnenberg A, Pedersen O, Walker M, Langenberg C, Scott RA, Wareham NJ20, Fritsche A, Häring HU, Stefan N, Groop L, O'Connell JR, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, März W, Kovacs P, Stumvoll M, Psaty BM, Kuusisto J, Laakso M52, Meigs JB, Dupuis J, Ingelsson E, Florez JC. Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci. Diabetes. 2016 Oct;65(10):3200-11. doi: 10.2337/db16-0199. Epub 2016 Jul 14.
Perry CG, Perry JA, Anforth LE, Pavlovich MA, Backman JD, Lewis JP, Ryan KA, O’Connell JR, Yerges-Armstrong LM, and Shuldiner AR. From Genotype to Phenotype: Nonsense Variants in SLC13A1 are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases. Genes, Genomes, and Genetics 2016 Sep 8;6(9):2909-18. doi: 10.1534/g3.116.032979.
Samant S, Jiang XL, Peletier LA, Shuldiner AR, Horenstein RB, Lewis JP, Lesko LJ, and Schmidt S. Identifying Clinically Relevant Sources of Variability: the Clopidogrel Challenge. Clin Pharmacol Ther 2016 Aug 24. doi: 10.1002/cpt.459
Wang H, Hong CE, Lewis JP, Zhu Y, Wang X, Chu X, Backman JD, Hu Z, Yang P, Still CD, Gerhard GS, Fu M. Effect of Two Lipoprotein (a)-Associated Genetic Variants on Plasminogen Levels and Fibrinolysis. Genes, Genomes, and Genetics 2016 Sep 7. pii: g3.116.034702. doi: 10.1534/g3.116.034702