SOM Faculty Profile : Stephen B Liggett

Stephen B Liggett

Stephen B Liggett M.D.

Academic Title: Professor

Primary Appointment: Medicine

Secondary Appointments: Physiology

sligg001@umaryland.edu

Location: HSF2, Room S116

Phone: (410) 706-6256

Fax: (410) 706-6262

Lab: (410) 706-6255

Personal History

Dr. Liggett obtained a B.S. in Physics from the Georgia Institute of Technology and an M.D. from the University of Miami School of Medicine. He served an Internship, Residency (Internal Medicine) and Fellowship (Pulmonary, Critical Care Medicine) at Washington University School of Medicine/Barnes Hospital in St. Louis. These were followed by a four year, laboratory-based post-doctoral fellowship at the Howard Hughes Medical Institute at Duke University in the laboratory of Robert Lefkowitz. He subsequently became an Assistant Professor of Medicine and Pharmacology at Duke University, and then Professor of Medicine, Pharmacology and Molecular Genetics at the University of Cincinnati College of Medicine, where he was also Director of Pulmonary and Critical Care Medicine. After 13 years as Division Director, he became the Taylor Endowed Professor of Medicine and Director of the Cardiopulmonary Research Center at UC, where he concentrated on his basic and translational research programs. In 2005 he moved to the University of Maryland School of Medicine, where he is Professor of Medicine and Physiology and Director of the Cardiopulmonary Genomics Program.

Research Interests

The laboratory has 4 major interrelated sections: 1) the study of the molecular basis of G-protein coupled receptor structure and function 2) delineation and characterization of human genetic variants within this receptor signaling network 3) association studies of genetic variants with heart and lung disease and their response to treatment (pharmacogenomics) to develop a platform for genetically-based personalized medicine and 4) creation of genetically modified mice to define the mechanisms of heart and lung disease and "humanized mice" to explore the effects of genetic variation of human genes. These studies have lead to new paradigms in our understanding of how this superfamily of receptors (the largest in the human genome) carry out signaling, how they participate in the pathophysiology of congestive heart failure and asthma, and how a patient's genetic makeup can be used to tailor drug treatment.

Publications

Selected Publications

Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB. Sequencing and analyses of all known human rhinovirus genomes reveals structure and evolution. Science 324:55-59, 2009.

Petrashevskaya N, Gaume BR, Mihlbachler KA, Dorn GW II, Liggett SB. Bitransgenesis with b2-adrenergic receptors or adenylyl cyclase fails to improve b1-adrenergic receptor cardiomyopathy. Clinical and Translational Science 1:221-227, 2008.

Kardia SLR, Kelly RJ, Keddache MA, Aronow BJ, Grabowski GA, Hahn HS, Case KL, Wagoner LE, Dorn GW II, Liggett SB. Multiple interactions between the a2C- and b1-adrenergic receptors influence heart failure survival. BMC Medical Genetics 9:93, 2008

Swift SM, Gaume BR, Small KM, Aronow BJ, Liggett SB. Differential coupling of Arg- and Gly389 polymorphic forms of the b1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs. Physiol Genomics 35:123-131, 2008.

Wang WCH, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB. A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of b2-adrenergic receptors. Pharmacogenet Genomics 18(8):729-732, 2008.

Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, Diwan A, Martini JS, Sparks L, Parekh RR, Spertus JA, Koch WJ, Kardia SLR, Dorn GW II. A G-protein coupled receptor kinase-5 polymorphism that inhibits b-adrenergic receptor signaling is protective in heart failure. Nature Medicine 14:510-517, 2008.

Liggett SB, Kelly RJ, Parekh RR, Matkovich SJ, Benner BJ, Hahn HS, Syed FM, Galvez AS, Case KL, McGuire N, Odley AM, Sparks L, Kardia SLR, Dorn GW II. A functional polymorphism of the Gaq (GNAQ) gene is associated with accelerated mortality in African American heart failure. Hum Mol Genet 16:2740-2750, 2007.

Liggett SB, Kelly RJ, Parekh RR, Matkovich SJ, Benner BJ, Hahn HS, Syed FM, Galvez AS, Case KL, McGuire N, Odley AM, Sparks L, Kardia SLR, Dorn GW II. A functional polymorphism of the Gaq (GNAQ) gene is associated with accelerated mortality in African American heart failure. Human Molecular Genetics 16:2740-2750, 2007.

Einstein R, Jordan H, Zhou W, Brenner M, Moses EG, Liggett SB. Alternative splicing of the G-protein coupled receptor superfamily in human airway smooth muscle diversifies the complement of receptors. Proc Nat Acad Sci 105(13):5230-5235, 2008.

Small KM, Mialet-Perez J, Liggett SB. Genetic variation within the b1-adrenergic receptor gene results in haplotype-specific expression phenotypes. J Cardiovasc Pharmacol 51:106-110, 2008.

Panebra A, Schwarb MR, Glinka CB, Liggett SB. Heterogeneity of transcription factor expression and regulation in human airway epithelial and smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 293:L453-L462, 2007.

McGraw DW, Elwing JM, Fogel KM, Wang WCH, Glinka CB, Mihlbachler KA, Rothenberg ME, Liggett SB. Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation. J Clin Invest 117:1391-1398, 2007.

Swift SM, Schwarb MR, Mihlbachler KA, Liggett SB. Pleiotropic b-agonist-promoted receptor conformations and signals independent of intrinsic activity. Am J Respir Cell Mol Biol 36:236-243, 2007.

McGraw DW, Fogel KM, Kong S, Kranias EG, Aronow BJ, Liggett SB. Transcriptional response to persistent b2-adrenergic receptor signaling reveals regulation of phospholamban which alters airway contractility. Physiol Genomics 27:171-177, 2006.

Liggett SB, Mialet-Perez J, Thaneemit-Chen S, Weber SA, Greene SM, Hodne D, Nelson B, Morrison J, Domanski MJ, Wagoner LE, Abraham WT, Anderson JL, Carlquist JF, Krause-Steinrauf HJ, Lazzeroni LC, Port JD, Lavori PW, Bristow MR. A polymorphism within a conserved b1-adrenergic receptor motif alters cardiac function and b-blocker response in human heart failure. Proc Nat Acad Sci 103(30):11288-11293, 2006.

McGraw DW, Mihlbachler KA, Schwarb MR, Rahman FF, Small KM, Almoosa KF, Liggett SB. Airway smooth muscle prostaglandin-EP1 receptors directly modulate b2-adrenergic receptors within a unique heterodimeric complex. J Clin Invest 116(5):1400-1409, 2006.

Small KM, Schwarb MR, Glinka C, Theiss CT, Brown KM, Seman CA, Liggett SB. a2A- and a2C adrenergic receptors form homo- and heterodimers: the heterodimeric state impairs agonist-promoted GRK phosphorylation and b-arrestin recruitment. Biochemistry 45:4760-4767, 2006.

Small KM, Brown KM, Seman CA, Theiss CT, Liggett SB. Complex haplotypes derived from non-coding polymorphisms of the intronless a2A-adrenergic gene diversify receptor expression. Proc Nat Acad Sci 103:5472-5477, 2006.

Tantisira KG, Small KM, Litonjua AA, Weiss ST, Liggett SB. Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase 9 in asthma: interaction between b-agonist and corticosteroid pathways. Hum Mol Genet 14:1671-1677, 2005.

Small KM, Mialet-Perez J, Seman CA, Theiss CT, Brown KM, Liggett SB. Polymorphisms of the cardiac presynaptic a2Cadrenergic receptors: diverse intragenic variability with haplotype-specific functional effects. Proc Nat Acad Sci 101:13020-13025, 2004.

Mialet-Perez J, Green SA, Miller WE, Liggett SB. A primate-dominant third glycosylation site of the b2-adrenergic receptor routes receptors to degradation during agonist regulation. J Biol Chem 279:38603-38607, 2004.

Perez JM, Rathz DA, Petrashevskaya NN, Hahn HS, Wagoner LE, Schwartz A, Dorn GW II, Liggett SB. b1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nature Medicine 9:1300-1305, 2003.

McGraw DW, Almoosa KF, Paul RJ, Kobilka BK, Liggett SB. Antithetic regulation by b-adrenergic receptors of Gq-receptor signaling via phospholipase-C underlies the airway b-agonist paradox. J Clin Invest 112:619-626, 2003.

Rathz DA, Gregory KN, Fang Y, Brown KM, Liggett SB. Hierarchy of polymorphic variation and desensitization permutations relative to b1- and b2-adrenergic receptor signaling. J Biol Chem 278:10784-10789, 2003.

Reviews of Interest

Liggett SB. Long-distance affair with adrenal GRK2 hangs up heart failure. Nature Medicine 13:246-248, 2007.

Liggett SB. Genetic variability of the b2-adrenergic receptor and asthma exacerbations. Thorax 61:925-927, 2006.

Liggett SB. Cardiac 7-TM receptor portfolios: diversify, diversify, diversify. J Clin Invest 116:875-877, 2006.

Liggett SB, Hall IP. b2-adrenergic receptor polymorphisms and asthmatic phenotypes. In: Genetics of Asthma and COPD. Edited by Postma DS and Weiss ST. Informa Healthcare, New York/London, 299-316, 2006.

Liggett SB. Genetically modified mouse models for pharmacogenomic research. Nature Reviews Genetics 5:657-663, 2004.

Liggett SB. The two-timing thyroid. Nature Medicine 10(6):582-583, 2004.

Small KM, McGraw DW, Liggett SB. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu Rev Pharmacol Toxicol 43:381-411, 2003.

Liggett SB. b-adrenergic receptors in the failing heart: the good, the bad, and the unknown. J Clin Invest 107:947-948, 2001.

Links of Interest

Visit My Lab

Faculty members: Click here to update your contact information and create a profile.