Last Updated: 6/25/2009
|Claire M Doerschuk, M.D.
Dr. Doerschuks research addresses host defense mechanisms in the lungs, particularly the inflammatory and innate immune processes that are important in the pathogenesis and course of bacterial pneumonia, acute lung injury/acute respiratory distress syndrome, and cigarette-smoke induced lung disease. Basic and translational studies address the mechanisms of host defense during pneumonia that focus on leukocyte recruitment, edema, and lung injury. These studies investigate pathogens that cause community-acquired and nosocomial pneumonias occurring in immunocompromised patients with cancer. Although these processes are important in all inflammatory lung diseases, her work particularly addresses pneumonia and the acute respiratory distress syndrome using in vivo, translational, cell biological, immunological, and molecular approaches. Her ultimate goal is to use this knowledge to develop therapies that enhance the inflammatory response when it is beneficial to the host and dampen this response when it is harmful.
Recruitment of leukocytes during pneumonia and other lung injuries
Leukocytes circulating in the blood stream are recruited to the site of infection in the lungs early in the inflammatory process. Dr. Doerschuk is interested in the mechanisms through which the lungs produce cytokines, chemokines and other regulatory inflammatory mediators in response to bacteria that then induce the production of other mediators and adhesion molecules on endothelial cells and result in the recruitment of leukocytes. Current studies address how leukocytes recognize sites of infection and how these mediators induce changes in the adhesivity and mechanical properties of neutrophils, usually the earliest leukocyte to respond and accumulate in the lungs.
Endothelial cell biology in normal lungs and during inflammatory and innate immune processes
The pulmonary microvascular endothelial cells have unique properties that regulate both fluid flux within the lungs and the migration of neutrophils from the blood stream into the lung tissue. These cells, along with epithelial cells within the airways and the airspaces, tightly regulate lung permeability and maintain a delicate balance of fluid flux. Major areas of study include the biology of adhesion molecules, including both their expression and function on endothelial cells and leukocytes. For example, ongoing studies determine the intracellular signaling pathways initiated by the ligation of the adhesion molecules ICAM-1 and E-selectin by their receptors on neutrophils and how these signaling pathways regulate transendothelial migration of neutrophils and fluid permeability. Another area of focus in Dr. Doerschuks lab is the function of the small GTPase Rac2, which she showed is expressed in endothelial cells and regulates both normal fluid flux and edema formation during injury.
Effector functions of leukocytes
Once leukocytes are recruited to the infection or other injury, they have many functions in resolving the infection. Neutrophils are important in clearing the bacteria and repairing any tissue damage. The mechanisms through which this is accomplished are an active area of study. For example, neutrophils have recently been shown to produce interferon-γ early in the course of some pneumonias through a very tightly regulated process that likely involves microRNAs. How the production of this molecule is regulated, its role in host defense, and the potential of this molecule as an important therapy in modulating host defense in immunocompromised patients are active areas of study.
Cigarette-smoke induced lung disease
Dr. Doerschuk also studies lung injuries induced by cigarette smoke that include chronic obstructive pulmonary disease (COPD), both emphysema and chronic bronchitis. Studies pursue the mechanisms through which cigarette smoke induces COPD and lung cancer.
Center for Airways Disease
Dr. Doerschuk also heads the new Center for Airways Disease. The Centers goal is to further our conceptual and mechanistic understanding of diseases that affect the airways of the lungs, particularly smoking-related diseases such as chronic obstructive pulmonary disease and lung cancer, as well as lung infections, including pneumonia. The Centers mission is to stimulate research that defines airways disease at a molecular level, enabling early diagnosis, prognosis and personalized treatment of patients with these lung diseases. The ultimate goal is to translate research findings into better care for residents of North Carolina and throughout the nation, addressing both the disease predictors and therapies and the social and behavioral aspects of these diseases.
Recent Accomplishments and Honors
American Lung Association Career Investigator Award, July, 1990 - 1995
Henry Pickering Bowditch Lectureship, American Physiological Society, Experimental Biology, 1993
American Thoracic Society Recognition Award for Scientific Accomplishment, 1998
Member, NHLBI PPG Parent Committee, 1998 - 2002
Membership in the American Society for Clinical Investigation, 1998
Fellow, American Association for the Advancement of Science, 1999
Elizabeth Rich M.D. Award, American Thoracic Society, 2003
Parker B. Francis Lectureship, American Thoracic Society International meeting, 2006
Chair, NIH Study Section, Lung Injury, Resolution and Repair, 2008 - 2010
Wellesley College, Wellesley, MA B.A. 1976 Mathematics
Rush University, Chicago, IL M.D. 1981 Medicine
University of Chicago, Chicago, IL Certification 1985 Pathology
University of British Columbia, Pulmonary Research Laboratory, Vancouver, BC Fellowship 1988 Experimental Pulmonary Pathology
1.Wang, Q., M. Yerukhimovich, W.A. Gaarde, I.J. Popoff, and C.M. Doerschuk. MKK3 and -6-dependent activation of p38α MAP kinase is required for cytoskeletal changes in pulmonary microvascular endothelial cells induced by ICAM-1 ligation. Am. J. Physiol.: Lung Cell. Mol. Physiol. 288:L359-L369, 2005.
2.Koss, M., G.R. Pfeiffer II, Y. Wang, S.T. Thomas, M. Yerukhimovich, W.A. Gaarde, C.M. Doerschuk and Q. Wang. Ezrin/radixin/moesin proteins are phosphorylated by TNF-α and modulate permeability increases in human pulmonary microvascular endothelial cells. J. Immunol. 176:1218-1227, 2006.
3.Yoshida, K., R. Kondo, Q. Wang, C.M. Doerschuk. Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats. Am. J. Respir. Crit. Care Med. 174:689-698, 2006.
4.Tatro, J.M., N. Taki, A.S. Islam, V.M. Goldberg, C.M. Rimnac, C.M. Doerschuk, M.C. Steward, and E.M. Greenfield. The balance between endotoxin accumulation and clearance during particle-induced osteolysis in murine calvaria. J. Orthop. Res. 25:391-399, 2006.
5.Vachon, E., R. Martin, V. Kwok, V. Cherepanov, C.W. Chow, C.M. Doerschuk, J. Plumb, S. Grinstein, and G.P. Downey. CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages. Blood 110: 4492-4502, 2007.
6.Doerschuk, C.M. Perspective: Pulmonary alveolar proteinosis: is host defense awry? New Engl. J. Med. 356:347-349, 2007.
7.Kang, I., D. Panneerselvam, C. Lee, V.P. Panoskaltsis, S.J. Eppell, R.E. Marchant, and C.M. Doerschuk. Determining the mechanical properties of living cells using atomic force microscopy and finite element modeling. Biophys. J. 94:3273-85, 2008.
8.Gomez, J.C., J. Soltys, K. Okano, M.C. Dinauer, and C.M. Doerschuk. The role of Rac2 in regulating neutrophil production in the bone marrow and circulating neutrophil counts. Am. J. Pathol. 173:507-17, 2008.
Telephone: 919 966-1077
FAX: 919 966-5178
Address: 7011 TB Chapel Hill, NC 27599
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