Division of Pulmonary and Critical Care
Basic Research Programs
The Cardiopulmonary Genomics Program is focused on understanding G-protein coupled receptor
signaling relevant to heart and lung disease. These efforts are centered on five complementary
areas: 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 to develop a platform for genetically-based personalized medicine,
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, and
5) determination of the full genome sequences of human Rhinoviruses using high throughput
next-generation sequencing technologies; analysis of the relationships between viral genomes
and asthma phenotypes. These studies are funded by five NIH grants.
- Deshpande DA, Wang, WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK,
Liggett SB. Bitter taste receptors on airway smooth muscle bronchodilate by
localized calcium signaling and reverse obstruction. Nature Medicine
doi:10.1038/nm.2237 (in press).
- Bristow MR, Murphy GA, Krause-Steinrauf H, Anderson JL, Carlquist JF, Thaneemit-Chen S,
Krishnan V, Abraham WT, Lowes BD, Port JD, Davis GW, Lazzeroni LC, Robertson AD, Lavori PW,
Liggett SB. An α2C-adrenergic receptor polymorphism alters the
norepinephrine-lowering effects and therapeutic response of the β-blocker bucindolol
in chronic heart failure. Circulation: Heart Failure 3:21-28, 2010.
- 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.
- Wang WCH, Mihlbachler KA, Brunnett AC, Liggett SB. Targeted transgenesis reveals
discreet attenuator functions of GRK and PKA in airway β2-adrenergic receptor physiologic
signaling. Proceedings of the National Academy of Sciences 106:15007-15012,
- 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 β-adrenergic receptor signaling is protective in heart failure.
Nature Medicine 14(5):510-517, 2008.
- 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. Proceedings of the National Academy of Sciences 105(13):5230-5235, 2008.
- 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. Journal of Clinical Investigation
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October 25, 2010.
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