Department of Anesthesiology/Critical Care Medicine
The Johns Hopkins University School of Medicine
600 North Wolfe Street, Meyer 298
Baltimore, MD 21287
Nauder Faraday, MD, completed his residency in Anesthesiology in 1992, a fellowship in Critical Care Medicine in 1993, and a fellowship in Cardiac Anesthesiology in 1994—all at JHU. He is currently the Director of Perioperative Genomic Research and of the Perioperative Hemostasis and Thrombosis Laboratory at JHU. He is funded by the NIH for investigation of the pharmacogenomics of antiplatelet agents for prevention of cardiovascular disease, for a genome-wide association study of platelet phenotypes, and for the study of the genotypic determinants of aspirin response in high-risk families; he also receives industrial sponsorship to investigate the safety and efficacy of rFVIIa in cardiac surgery.
In addition to these sponsored activities, Dr. Faraday conducts ongoing translational and clinical research programs in platelet biology and perioperative genomics. Translational projects use in vitro and vivo models to identify the mechanisms through which inflammation promotes platelet-mediated thrombosis. Dr. Faraday has assembled a multidisciplinary team that conducts a prospective cohort study to investigate the genetic basis for infectious and thrombotic outcomes after surgery. A summary of the goals of the preoperative genomic research program follows:
Infectious (wound, bloodstream, pulmonary) and vascular occlusive (myocardial infarction, venous thromboembolism) complications occur in as many as 20% of surgical patients and represent a significant source of preventable morbidity and mortality. Identification of patients at highest risk for these complications and alteration of medical therapy to mitigate their risk is an attractive approach toward improving patient safety and outcomes. Unfortunately, currently available risk-prediction tools that are based on medical history and surgical criteria have insufficient predictive power to guide medical decision making.
Dr. Faraday and his colleagues hypothesize that patient genetic factors account for a substantial proportion of the inter-individual variance in the development of postoperative complications and that the combination of genetic and clinical factors will improve the accuracy of risk models that are based on clinical criteria alone. The have designed a study to (a) identify genetic determinants of infectious and vascular occlusive complications in patients who undergo surgical procedures associated with a high incidence of infectious and vascular thrombotic complications, and (b) combine genetic and clinical information to develop risk-prediction tools that allow physicians to tailor therapy according to individual patient risk. To accomplish these goals, they are conducting a prospective observational study in 2500 “clean” surgical procedures, i.e., cardiac, vascular, spinal, and intracranial surgery. Cases of infectious and thrombotic complications will be identified from review of the medical records and interviews of patients and their physicians. Nasal colonization with Staphylococcus aureus is evaluated as an intermediate infectious outcome measure because of its high prevalence (~20%–30%) and strong relation to the subsequent development of wound, bloodstream, and pulmonary infection after these surgical procedures. Using the Illumina high-throughput platform, variants in ~150 candidate immunity- and hemostasis-related genes are identified from genomic DNA. Multivariable regression is used to determine the relationship between gene variants and each outcome measure. Clinical and genetic data are integrated to develop risk models for each outcome measure, and their predictive power as determined from receiver-operator characteristic analysis. The ultimate goal of Dr. Faraday’s research is to construct predictive tools that will allow targeted use of novel antimicrobial and antithrombotic strategies, which maximize benefit and minimize risk to individual patients.
- American Society of Anesthesiologists
- International Anesthesia Research Society
- Society of Cardiovascular Anesthesiologists
- Society of Critical Care Medicine
- American Medical Association
- Faraday N, Becker DM, Yanek YR, Herrera-Galeano JE, Segal JB, Moy TF, Bray PF, Becker LC. Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population. Am J Cardiol 98:774–9, 2006.
- Faraday N, Yanek LR, Mathias R, Herrera-Galeano JE, Vaidya D, Moy TF, Fallin MD, Wilson AF, Bray PF, Becker LC, Becker DM. Heritability of platelet responsiveness to aspirin in activation pathways directly and indirectly related to cyclooxygenase-1. Circulation 115:2490–6, 2007.
- Bray PF, Mathias RA, Faraday N, Yanek LR, Fallin MD, Herrera-Galeano JE, Wilson AF, Becker LC, Becker DM. Heritability of platelet function in families with premature coronary artery disease. J Thromb Haemost 5:1617–23, 2007.
- Bordeaux B, Yanek LR, Moy TF, White LW, Becker LC, Faraday N, Becker DM. Casual chocolate consumption and inhibition of platelet function. Prev Cardiol 10: 175–80, 2007.
- Faraday N, Becker DM, Becker LC. Pharmacogenomics of platelet responsiveness to aspirin. Pharmacogenomics 8:1413–25, 2007.
- Morrell CN, Sun H, Ikeda M, Beique JC, Swaim AM, Mason E, Martin TV, Thompson LE, Gozen O, Ampagoomian D, Sprengel R, Rothstein J, Faraday N, Huganir R, Lowenstein CJ. Glutamate mediates platelet activation through the AMPA receptor. J Exp Med 205:575–84, 2008
Laboratory Members/Key Associates
Angela McFillin, BS
Polly Robarts, BA
Elizabeth White, RN
Michelle Parish, RN
Susan Townsend, RN
Kate Schunke, PhD
Craig Morrell, DVM, PhD
Hui Zhang, PhD
Ray Koehler, PhD
Sylvain Dore, PhD
Lewis Becker, MD
Diane Becker, ScD
Alan Shuldiner, MD
Eliseo Guallar, MD, DrPH
- Alpha Omega Alpha Honor Society
- Association of University Anesthetists
- Association of Cardiac Anesthesiologists