Genomics approach to drug discovery and personalized medicine
is the Vice Dean for Research at USF’s Morsani College of Medicine. His lab
studies the genetics, genomics, and molecular and cellular biology of G-protein
coupled receptors (GPCRs). He discovered
the first nonsynonymous polymorphism of a GPCR, subsequently defining its
function in cells and genetically modified mice. GPCRs are the targets of ~50%
of currently prescribed drugs.
Delineation for the extensive variability within the superfamily opened
the modern era of pharmacogenomics, where drug targets are now considered. The
laboratory studies GPCRs in relation to heart and lung disease, but casts a
broad net to understand inter-individual variability. For example, the group
preformed complete genome sequencing of all known human rhinoviruses. This lead
to superimposition of crystal structures, optimal-energy RNA conformation
predictions, and phylogeny to ascertain the basis of rhinovirus induced GPCR
dysfunction and asthma pathogenesis.
Pera T, Liggett SB, Benovic JL, Penn RB.
Pepducins as a potential treatment strategy for asthma and COPD.
Curr Opin Pharmacol. 2018 Jun;40:120-125. doi:
10.1016/j.coph.2018.04.008. Epub 2018 May 2. Review.
Genetic Vulnerability of GPCRs: A Call to Action.
Trends Biochem Sci. 2018 Apr;43(4):227-229. doi:
Xu H, Dorn GW
2nd, Shetty A, Parihar A, Dave T, Robinson SW, Gottlieb SS, Donahue MP,
Tomaselli GF, Kraus WE, Mitchell BD, Liggett SB.
A Genome-Wide Association Study of Idiopathic Dilated
Cardiomyopathy in African Americans.
J Pers Med. 2018 Feb 26;8(1). pii: E11. doi:
Kim D, Cho S,
Woo JA, Liggett SB.
A CREB-mediated increase in miRNA let-7f during prolonged
β-agonist exposure: a novel mechanism of β2-adrenergic receptor
down-regulation in airway smooth muscle.
FASEB J. 2018 Jul;32(7):3680-3688. doi:
10.1096/fj.201701278R. Epub 2018 Feb 13.
An SS, Liggett
Taste and smell GPCRs in the lung: Evidence for a previously
unrecognized widespread chemosensory system.
Cell Signal. 2018 Jan;41:82-88. doi: 10.1016/j.cellsig.2017.02.002.
Epub 2017 Feb 4. Review.
Kim D, Woo JA,
Geffken E, An SS, Liggett SB.
Coupling of Airway Smooth Muscle Bitter Taste Receptors to
Intracellular Signaling and Relaxation Is via Gαi1,2,3.
Am J Respir Cell Mol Biol. 2017 Jun;56(6):762-771.
Kim D, Pauer SH, Yong HM, An SS, Liggett SP. 2016. β2-Adrenergic Receptors Chaperone Trapped Bitter Taste Receptor 14 to the Cell Surface as a Heterodimer and Exert Unidirectional Desensitization of Taste Receptor Function. J Biol Chem 291(34):17616-28.
Fox CS, Hall JL, Arnett DK, Ashley EA, Delles C, Engler MB, Freeman MW, Johnson JA, Lanfear DE, Liggett SB, Lusis AJ,Loscalzo J, MacRae CA, Musunuru K, Newby LK, O'Donnell CJ, Rich SS, Terzic A; American Heart Association Council on Functional Genomics and Translational Biology, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Quality of Care and Outcomes Research, and Council on Epidemiology and Prevention. 2015. Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association. Circulation 131(19):1715-36.
Bridges TM, Scheraga RG, Tulapurkar ME, Suffredini D, Liggett SB, Ramarathnam A, Potla R, Singh IS, Hasday JD. 2015. Polymorphisms in human heat shock factor-1 and analysis of potential biological consequences. Cell Stress Chaperones 20(1):47-59.
Taylor MR, Sun AY, Davis G, Fiuzat M, Liggett SB, Bristow MR. 2014. Race, common genetic variation, and therapeutic response disparities in heart failure. JACC Heart Fail 2(6):561-72.
Wang WC, Pauer SH, Smith DC, Dixon MA, Disimile DJ, Panebra A, An SS, Camoretti-Mercado B, Liggett SB. 2014. Targeted transgenesis identifies Gαs as the bottleneck in β2-adrenergic receptor cell signaling and physiological function in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 307(10):L775-80.
Liggett SB, Bochkov YA, Pappas T, Lemanshe RF Jr, Gern JE, Sengamalay N, Zhao X, Su Q, Fraser CM, Palmenberg AC. 2014. Genome sewuences of rhinovirus a isolates from Wisconsin pediatric repsiratory studies. Genome Announc 2(2). pii: e00200-14.
Aleong RG, Sauer WH, Robertson AD, Liggett SB, Bristow MR. 2013. Adrenergic receptor polymorphisms and prevention of ventricular arrhythmias with bucindolol in patients with chronic heart failure. Circ Arrhythm Electrophysiol 6(1):137-43.
O'Connor CM1, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA, Lindenfeld J, Miller AB, White M, Walsh R, Nelson P, Medway A, Davis G, Robertson AD, Port JD, Carr J, Murphy GA, Lazzeroni LC, Abraham WT, Liggett SB, Bristow MR. Combinatorial pharmacogenetic interactions of bucindolol and β1, α2C adrenergic receptor polymorphisms. PLoS One 7(10):e44324.
Bochkov YA, Palmenberg AC, Lee W-M, Rathe JA, Amineva SP, Sun X, Pasic TR, Jarjour NN, Liggett SB, Gern JE. 2011. Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med 17:627–32.
Wang WCH, Schillinger RM, Malone MM, Liggett SB. 2011. Paradoxical attenuation of β2-AR function in airway smooth muscle by Gi-mediated counterregulation in transgenic mice overexpressing type 5 adenylyl cyclase. Am J Physiol Lung Cell Mol Physiol 300:L472-8.
Wang WC, Juan AH, Panebra A, Liggett SB. 2011. MicroRNA let-7
establishes expression of 2-adrenergic receptors and dynamically
down-regulates agonist-promoted down-regulation. Proc Nat Acad Sci
Parsa A, Chang Y-PC, Kelly RJ, Corretti MC, Ryan KA, Robinson SW, Gottlieb SS, Kardia SLR, Shuldiner AR, Liggett SB. 2011. Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality. Clin Transl Sci 4:17–23.
Rathe JA, Liu X, Tallon LJ, Gern JE, Liggett SB. 2010. Full-genome sequence and analysis of a novel human rhinovirus strain within a divergent HRV-A clade. Arch Virol 155:83–7.