Debra A. Schwinn, M.D., has been selected to receive the American Society of Anesthesiologists 2007 Excellence in Research Award. This purpose of this award is to recognize an individual's work that represents a body of original, mature, and sustained contribution to the advancement of the science of anesthesiology. Dr. Schwinn not only embodies these attributes but also provides an example to us all of how a physician–scientist uniquely contributes to the overall mission of advancing patient care.

Dr. Schwinn, a native of Ohio, completed her undergraduate studies in chemistry at the College of Wooster, Wooster, Ohio, in 1979. In 1983, she was awarded her M.D. degree from Stanford University, Stanford, California. Her internship and residency were performed at the University of Pennsylvania (Philadelphia), followed by a clinical cardiac anesthesiology fellowship completed in 1987 at Duke University, Durham, North Carolina. This extraordinary medical training would have met most people's definition of a long road. However, for Dr. Schwinn there was still 5 yr to go. She recognized excellence in the laboratory of Robert J. Lefkowitz, M.D., a Professor of Medicine and Biochemistry at Duke whose work has pioneered elucidation of the molecular properties and regulatory mechanisms controlling the function of G protein–coupled receptors. G protein–coupled receptors provide the signal transduction mechanism for a plethora of ligands well known to anesthesiologists, including adenosine, γ-aminobutyric acid, vasopressin, histamine, dopamine, norepinephrine, epinephrine, acetylcholine, serotonin, and others. Dr. Schwinn, while continuing her work as a cardiac anesthesiologist, immersed herself in the Lefkowitz laboratory from 1987 to 1992, learning the molecular biologic techniques that would support the balance of her investigative career. During this time, Dr. Schwinn made fundamental discoveries in the field of α1-adrenergic receptors (α1ARs) that would allow her to bring translational molecular biology into the cardiac operating room, as well as extension to studies of benign prostatic hypertrophy,1neurologic disease,2and ophthalmology.3After 5 yr of research training, Dr. Schwinn established the Molecular Pharmacology Laboratory within the Department of Anesthesiology at Duke. She rapidly rose through the academic ranks to be promoted to Professor in 1998 within the Departments of Anesthesiology, Surgery, and Pharmacology/Cancer Biology.

Dr. Schwinn's scholarly achievements are extraordinary. She has published well over 100 peer-reviewed articles, many of which have been in Anesthesiology, Circulation Research , Circulation , Journal of Biologic Chemistry  (of which she is an editorial board member), Nature , Proceedings of the National Academy of Sciences , and so on. The National Institutes of Health has funded Dr. Schwinn's work since 1990, most of that time with multiple simultaneous awards. She served as a full-term member of two successive National Institutes of Health study sections from 1993 to 2000. Her performance was outstanding. Therefore, she was selected to serve as a member of the National Institute of General Medical Sciences Advisory Council from 2000 to 2004. In addition, she has served a full term as a grant reviewer and member of scientific advisory committee for the Foundation for Anesthesia Education and Research, sits on the International Anesthesia Research Society Board of Trustees and the Scientific Board of the Sarnoff Cardiovascular Research Foundation, and provides leadership roles in multiple philanthropic funding agencies. Her excellence has been recognized by her induction into the Institute of Medicine of the National Academies, Alpha Omega Alpha, and the Association of American Physicians. She has broad international recognition as both a research scientist and an individual who can translate research discoveries into clinical practice. Of note, Duke recently opened an Institute for Genome Sciences and Policy. Among many prominent cardiovascular scientists at Duke, most being in the departments of Medicine and Surgery, Deb was selected as the Program Director for Cardiovascular Genomics. These sorts of activities have had enormous impact in making the field of anesthesiology not only a player, but even more so a leader in cutting edge genomic science.

Dr. Schwinn has not overlooked the importance of science education. Duke has a peculiar system in the medical school in which third-year students spend a full year doing research. Deb has served as the director of this program and has helped to formalize the process for students who wish to spend a second year in the laboratory to earn a master's degree in addition to the M.D. In her own laboratory, she has provided hands-on training of a plethora of individuals, spanning the range of teaching high school students to serving as the primary mentor of basic science doctoral candidates. Most of her many trainees have remained in research careers, with numerous individuals having achieved independent investigator status. Duke recently opened a new medical school in Singapore, and Dr. Schwinn led the development of research training of medical students, mirroring the system in place in Durham. Dr. Schwinn has also authored peer-reviewed articles pertaining to research training, the most recent of which was a seminal article in Anesthesiology proposing a solution to the very real problem of the declining number of formally trained physician–scientists in our specialty.4 

Despite all of this, Dr. Schwinn's greatest achievements have been in her laboratory and in how she has translated those discoveries into anesthesiology and the broader field of clinical medicine. Her laboratory combines molecular pharmacology approaches with translational human functional genomics to study mechanisms underlying regulation of adrenergic receptors in health and disease. She focuses primarily on regulation of the G protein–coupled α1aARs, which she discovered as a research fellow in Dr. Lefkowitz's laboratory. Because these receptors are important in smooth muscle and the heart, diseases such as hypertension and myocardial hypertrophy are the main foci. However, it is of note that her discoveries have also had major impact in the field of urology because of the relevance of her signal transduction work to understanding the pathogenesis of benign prostatic hypertrophy.

Three α1AR subtypes exist (α1a, α1b, and α1d). Over the years, Dr. Schwinn was involved in cloning complementary DNAs encoding each of these subtypes from both animal and human sources,5–8and demonstrated that α1aARs are present and functional in human vasculature (particularly resistance vessels and coronary arteries) and modified by age.9To understand mechanisms underlying these changes, her laboratory examines regulation of the human α1aAR at transcriptional and protein levels10–12in the presence and absence of hypoxia.13Within this context, she is pursuing an emerging line of investigation that may play a key role in the uniqueness of the α1aAR in continued signaling in the presence of agonist in situations where other G protein–coupled adrenergic receptors, such as α1band α1d, concurrently desensitize and/or down-regulate signaling. Her laboratory has demonstrated that the α1aAR, but not the α1bAR, undergoes constitutive internalization in the absence of agonist, suggesting that internalized α1aARs may use alternative trafficking pathways.14Recent data suggest that this may be due to compartmentalization of the α1aAR to lipid-enriched regions of the plasma membrane termed lipid rafts , thereby restricting coupling of the receptor to distinct subsets of intracellular signaling molecules. Dr. Schwinn is using the power of chromatin immunoprecipitation and microarray analysis to extend these studies to elucidate dynamic transcriptional mechanisms that reprogram in cellular gene expression.15,16Because of these studies, her laboratory was asked to write the definitive α1aAR UCSD–Nature molecule page (Nature , 2006; doi: 10.1038/mp.a000007.01).

Despite her already extraordinary training, Dr. Schwinn recognized an emerging field that could have dramatic implications for anesthetized and/or critically ill patients. In 2000, she received extramural funding to conduct a sabbatical at the National Human Genome Research Institute (Bethesda, Maryland) to be trained to perform functional genomics research. She transferred this knowledge to her laboratory, with recent emphasis on study of the role of genetic variability on human cardiovascular disease. Specifically, the role of naturally occurring single nucleotide polymorphisms and insertions/deletions of α1-AR signaling is being investigated.17These studies use classic genetic approaches; large-scale genomic sequencing, single nucleotide polymorphism identification, and analysis for association with disease in highly phenotyped populations. It also includes investigating the biology of each single nucleotide polymorphism in terms of α1AR signal transduction pathways by using microarray and proteomics approaches.

This work has positioned Dr. Schwinn to postulate that reproducible perioperative stress represents a unique paradigm for understanding the effects of acute and chronic stress. Of particular relevance to anesthesiology, her group is studying how genetic variability can be used to predict (and intervene to prevent) adverse outcomes in the perioperative period. An explosion of articles resulted from this work, including the role of functional genomics in perioperative sepsis,18stroke and cognitive decline,19,20renal failure,21and myocardial responses to cardiopulmonary bypass.22,23This work ushered in a new era of the operating room as a laboratory for study of human responses to physiologic stress,24,25the implications of which will likely transform our approach to patient care for decades.

Dr. Schwinn is a leading scientist in cardiovascular medicine bringing into anesthesiology the science of genomics, but at the same time making the specialty of anesthesiology a leader in this field. She does all of this while being a physician, mentor, mother of two daughters, a friend of most if not all scientists in our specialty, a communicator to clinicians, and a role model to which virtually all of us aspire. Deb's vision for the role of science in anesthesiology is prescient. She is a giant in our specialty, and we are thrilled she has received the 2007 Excellence in Research Award.

However, her journey does not end here. To be sure, Dr. Schwinn had incredible collaborators who allowed her vision to become reality. I am certain that they all take pleasure in her receipt of this award because it reflects their work as well. At the same time, Dr. Schwinn has recently accepted a new challenge, that of being Professor and Chair of the Department of Anesthesiology at the University of Washington (Seattle). We hope her new colleagues also take pride in Dr. Schwinn's receipt of the American Society of Anesthesiologists 2007 Excellence in Research Award. In her, they will find a tireless soul dedicated to breakthrough medicine based on rigorous scientific inquiry and discovery. They will also find in her an individual who has walked the walk, making the personal sacrifices necessary to be equipped to make these discoveries, and one who realizes that anesthesiologists have not only a mandate to provide patient care, but also a responsibility to advance it.

Figure. Debra A. Schwinn, M.D., recipient of the American Society of Anesthesiologists 2007 Excellence in Research Award .

Figure. Debra A. Schwinn, M.D., recipient of the American Society of Anesthesiologists 2007 Excellence in Research Award .

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Roehrborn CG, Schwinn DA: Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 2004; 171:1029–35
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; 135:507–23
Schwinn DA, Afshari NA: α1-Adrenergic receptor antagonists and the iris: new mechanistic insights into floppy iris syndrome. Surv Ophthalmol 2006; 51:501–12
Schwinn DA, Balser JR: Anesthesiology physician scientists in academic medicine: A wake-up call. Anesthesiology 2006; 104:170–8
Cotecchia S, Schwinn DA, Randall RR, Lefkowitz RJ, Caron MG, Kobilka BK: Molecular cloning and expression of the cDNA for the hamster alpha 1-adrenergic receptor. Proc Natl Acad Sci U S A 1988; 85:7159–63
Schwinn DA, Lomasney JW, Lorenz W, Szklut PJ, Fremeau RT Jr, Yang-Feng TL, Caron MG, Lefkowitz RJ, Cotecchia S: Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype. J Biol Chem 1990; 265:8183–9
Lomasney JW, Cotecchia S, Lorenz W, Leung WY, Schwinn DA, Yang-Feng TL, Brownstein M, Lefkowitz RJ, Caron MG: Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor: The gene for which is located on human chromosome 5. J Biol Chem 1991; 266:6365–9
Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: Sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther 1995; 272:134–42
et al.
Rudner XL, Berkowitz DE, Booth JV, Funk BL, Cozart KL, D'Amico EB, El-Moalem H, Page SO, Richardson CD, Winters B, Marucci L, Schwinn DA: Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation 1999; 100:2336–43
Razik MA, Lee K, Price RR, Williams MR, Ongjoco RR, Dole MK, Rudner XL, Kwatra MM, Schwinn DA: Transcriptional regulation of the human alpha1a-adrenergic receptor gene: Characterization of the 5′-regulatory and promoter region. J Biol Chem 1997; 272:28237–46
Price RR, Morris DP, Biswas G, Smith MP, Schwinn DA: Acute agonist-mediated desensitization of the human alpha 1a-adrenergic receptor is primarily independent of carboxyl terminus regulation: Implications for regulation of alpha 1aAR splice variants. J Biol Chem 2002; 277:9570–9
Hawrylyshyn KA, Michelotti GA, Coge F, Guenin SP, Schwinn DA: Update on human alpha1-adrenoceptor subtype signaling and genomic organization. Trends Pharmacol Sci 2004; 25:449–55
Michelotti GA, Bauman MJ, Smith MP, Schwinn DA: Cloning and characterization of the rat alpha 1a-adrenergic receptor gene promoter: Demonstration of cell specificity and regulation by hypoxia. J Biol Chem 2003; 278:8693–705
Morris DP, Price RR, Smith MP, Lei B, Schwinn DA: Cellular trafficking of human alpha1a-adrenergic receptors is continuous and primarily agonist-independent. Mol Pharmacol 2004; 66:843–54
Michelotti GA, Brinkley DM, Morris DP, Smith MP, Louie RJ, Schwinn DA: Epigenetic regulation of human (alpha)1d-adrenergic receptor gene expression: A role for DNA methylation in Sp1-dependent regulation [published online ahead of print March 23, 2007]. FASEB J 2007; 21:1979–93
Morris DP, Michelotti GA, Schwinn DA: Evidence that phosphorylation of the RNA polymerase II carboxyl-terminal repeats is similar in yeast and humans. J Biol Chem 2005; 280:31368–77
Lei B, Morris DP, Smith MP, Svetkey LP, Newman MF, Rotter JI, Buchanan TA, Beckstrom-Sternberg SM, Green ED, Schwinn DA: Novel human alpha1a-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function. Naunyn Schmiedebergs Arch Pharmacol 2005; 371:229–39
Moretti EW, Morris RW, Podgoreanu M, Schwinn DA, Newman MF, Bennett E, Moulin VG, Mba UU, Laskowitz DT: APOE polymorphism is associated with risk of severe sepsis in surgical patients. Crit Care Med 2005; 33:2521–6
Grocott HP, White WD, Morris RW, Podgoreanu MV, Mathew JP, Nielsen DM, Schwinn DA, Newman MF: Genetic polymorphisms and the risk of stroke after cardiac surgery. Stroke 2005; 36:1854–8
Mathew JP, Podgoreanu MV, Grocott HP, White WD, Morris RW, Stafford-Smith M, Mackensen GB, Rinder CS, Blumenthal JA, Schwinn DA, Newman MF: Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery. J Am Coll Cardiol 2007; 49:1934–42
Stafford-Smith M, Podgoreanu M, Swaminathan M, Phillips-Bute B, Mathew JP, Hauser EH, Winn MP, Milano C, Nielsen DM, Smith M, Morris R, Newman MF, Schwinn DA: Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis 2005; 45:519–30
Podgoreanu MV, Schwinn DA: Genomics and the circulation. Br J Anaesth 2004; 93:140–8
Podgoreanu MV, Michelotti GA, Sato Y, Smith MP, Lin S, Morris RW, Grocott HP, Mathew JP, Schwinn DA: Differential cardiac gene expression during cardiopulmonary bypass: Ischemia-independent upregulation of proinflammatory genes. J Thorac Cardiovasc Surg 2005; 130:330–9
Schwinn DA, Podgoreanu M: The new age of medical genomics. Br J Anaesth 2005; 95:119–21
Podgoreanu MV, Schwinn DA: New paradigms in cardiovascular medicine: Emerging technologies and practices: perioperative genomics. J Am Coll Cardiol 2005; 46:1965–77