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Molecular Pharmacology Laboratory
Our laboratory combines molecular pharmacology approaches with translational human functional genomics. The main emphasis of this laboratory is understanding mechanisms underlying alpha1-adrenergic receptor regulation in health and disease, as well as the role of genetics in predicting perioperative outcomes after heart surgery. In the laboratory, since alpha1-adrenergic receptors are important in smooth muscle and the heart, diseases such as hypertension and myocardial hypertrophy are our main foci. Studies range from examining fundamental transcriptional mechanisms and cell signaling, to mutagenesis to determine the role of specific amino acids in regulatory processes, through clinical interventional trials. Pharmacologic endpoints are used to assay for effects on receptor function, augmented by biochemical and genomic approaches. A recent emphasis in the laboratory is the role of genetic variability on human cardiovascular disease; specifically the role of naturally occurring single nucleotide polymorphisms (SNPs) and insertions/deletions of alpha1-adrenergic receptors, as well as genetic variants in many other genes, in predicting adverse perioperative outomes is being investigated. This involves using classical genetic approaches, large scale genomic sequencing, SNP identification, analysis for association with disease in highly phenotyped populations, comparison of our findings with whole genome scans, and proteomic/microarray approaches to enhance SNP selection from a more unbiased perspective. Interventions designed to improve (minimize) adverse outcomes, based on our recent findings, are planned for the future. Students/fellows/faculty can pick from a variety of projects related to their specific area(s) of interest within medicine.
Representative Publications
- Schwinn DA, Podgoreanu MV. The New Age of Medical Genomics. Br J Anaes August 2005; 95: 119-121
- Morris DP, Michelotti GA, Schwinn DA. Evidence that phosphorylation of RNA polymerase II C-terminal
repeats during transcription is similar in yeast and humans. J Biol Chem 2005; 280 : 31368-77
- Schambra UB, Mackensen GB, Stafford-Smith M, Haines DE, Schwinn DA. Neuron specific alpha-adrenergic
receptor expression in human cerebellum: implications for emerging cerebellar roles in neurologic disease. Neuroscience 2005; 135 : 507-523
- Grocott HP, White WD, Morris RW, Podgoreanu MV, Mathew JP, Schwinn DA, Newman MF, for the PEGASUS Investigators. Genetic polymorphisms and the risk of stroke after cardiac surgery. Stroke 2005 Sep;369:1854-8
- Podgoreanu MV, Michelotti GA, Sato Y, Smith MP, Lin S, Grocott HP, Booth JV, Schwinn DA. Differential cardiac gene expression during cardiopulmonary bypass: ischemia-independent upregulation of pro-inflammatory genes. J Thorac Cardiov Sur 2005; 130 : 330-339
- Lei B, Morris DP, Smith MP, Svetkey L, Newman M, Rotter JI, Buchanan T, Beckstrom-Sternberg SM, Green, ED, Schwinn DA. Novel human alpha1a-adrenergic receptor single nucleotide polymorphisms alter receptor biological function. Naunyn Schmiedeberg’s Arch Pharmacol 2005; 371: 229-23
- Podgoreanu MV & Schwinn DA. New Paradigms in Cardiovascular Medicine. Emerging Technologies and Practices: Perioperative Genomics. J Am Coll Cardiol 2005; 46: 1965-1977
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Debra A. Schwinn, MD
James B. Duke Professor of Anesthesiology
Professor of Pharmacology/Cancer Biology
Professor of Medicine (Cardiology) & Surgery
Program Director for Cardiovascular Genomics, Duke IGSP
Office: (919) 681-47841
E-mail: schwi001@mc.duke.edu
Laboratory staff members:
Gregory A. Michelotti, PhD, Research Assistant Professor
Daniel P. Morris, PhD, Research Assistant Professor
Yue-Xuan Wu, PhD, Senior Research Associate
Beilei Lei, MD, PhD, Research Associate
Michael P. Smith, Research Analyst II
Joshua K. Jordan, Research Technician II
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