Program Description
The primary focus of our laboratory is to understand the signaling pathways evoked by G-protein-coupled receptors (GPCRs) and the role of specific gene protein pathways in the pathogenesis of asthma and other allergic diseases. Although therapeutic agents targeting GPCRs have long been used to treat asthma and allergies, much remains unknown about how their signaling cascades drive the immune system. Our section focuses on the role of a family of inhibitory proteins known as regulators of G protein signaling (RGS). Our goals are to understand specific GPCRs, G proteins, and RGS proteins that mediate three distinct but overlapping processes: 1) migration of leukocytes to inflammatory sites; 2) bronchial smooth muscle contraction and relaxation; and 3) vascular permeability. We use mouse models of skin and pulmonary inflammation as well as clinical studies. Of particular interest is a rare and highly unusual disorder, the systemic capillary leak syndrome. This disease is characterized by reversible episodes of hypovolemia, hypotensive shock, and ansarca, which are thought to be a result of transient endothelial hyperpermeability.
Biography
Dr. Druey obtained his M.D. from Rush Medical College in Chicago, Illinois. In 1992, following a residency in internal medicine at The New York Hospital/Cornell Medical Center, Dr. Druey became a postdoctoral fellow in the NIAID Laboratory of Immunoregulation. He joined the Laboratory of Allergic Diseases in 1997 to become chief of the Molecular Signal Transduction Section (MSTS).
Research Group
Zhihui (Sherry) Xie, Ph.D., Staff Scientist
Tolga Barker, Ph.D. , Postdoctoral Fellow
Nariman Balenga, Ph.D., Postdoctoral Fellow
Sucharita Shankar, Ph.D., Postdoctoral Fellow
Shoko Iwaki, M.D., Ph.D., Biologist
Selected Publications
Yang Z, Cooper PR, Damera G, Mukhopadhyay I, Cho H, Kehrl JH, Panettieri RA Jr, Druey KM. Beta-agonist-associated reduction in RGS5 expression promotes airway smooth muscle hyper-responsiveness. J Biol Chem. 2011 Apr 1;286(13):11444-55.
Druey KM, Greipp PR. Narrative review: the systemic capillary leak syndrome. Ann Intern Med. 2010 Jul 20;153(2):90-8.
Bansal G, DiVietro JA, Kuehn HS, Rao S, Nocka KH, Gilfillan AM, Druey KM. RGS13 controls G-protein-coupled receptor-evoked responses of human mast cells. J Immunol. 2008 Dec 1;181(11):7882-90.
Xie Z, Geiger TR, Johnson EN, Nyborg JK, Druey KM. RGS13 acts as a nuclear repressor of CREB. Mol Cell. 2008 Sep 5;31(5):660-70.
Bansal G, Xie Z, Rao S, Nocka KH, Druey KM. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat Immunol. 2008 Jan;9(1):73-80.
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