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Research
Interests |
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We have two major research interests: 1) Molecular mechanisms of lung fibrosis and its inhibition by growth factors: Because of its location and function, the lung is vulnerable to a variety of insults. These insults could be drug induced (during chemotherapy) or due to exposure to infectious agents, allergens or other adverse conditions. Insults to the lung cause injury and abnormal repair of the injury can result in fibrosis, which inhibits normal lung function. We and others have shown that growth factors like KGF, whose activity is largely restricted to epithelial cells, can protect lungs from injury and inhibit fibrosis. Using inducible transgenic and knockout mice, yeast two-hybrid system, microarray approaches and imaging technology we are addressing the molecular mechanisms downstream of these biological signals that cause inhibition of fibrosis. 2) Understanding the mechanism of drug- and environment-induced changes in lung microenvironment that can influence dendritic cell (DC) function: In the lung, DCs and epithelial cells exist in close apposition. Drug therapy, allergen exposure or infection can alter the cytokine-chemokine milieu in the tissue. This altered microenvironment can influence DC function directly or through epithelial cells. We have shown that statin, a cholesterol-lowering agent, can influence DC character and this statin-exposed DC induces a Th2 bias in the immune response. Also, DCs in contact with the lung epithelium have reduced expression of TLR9. We are investigating whether altered DC properties have any consequence in the pathogenesis of cystic fibrosis and airway remodeling in asthma.
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Selected
Publications |
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- Arora M, Chen L, Paglia M, Gallagher I, Allen JE, Vyas YM, Ray A, Ray P. Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells. Proc Natl Acad Sci USA 103:7777-7782. 2006.
- Chen Li, Arora M, Yarlagadda M, Oriss T, Krishnamoorthy N, Ray A, Ray P. Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide1. J Immunol 177: 2373-2383.
- Pan ZZ, Devaux Y, Ray P. Ribosomal S6 Kinase as a mediator of Keratinocyte Growth Factor-Induced Activation of Akt in Epithelial Cells. Mol Biol Cell 15:3106-3113. 2004.
- Ray P, Devaux Y, Stolz DB, Yarlagadda M, Watkins SC, Liu W, Lu Y, Yang XF, Ray A. Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia. Proc Natl Acad Sci USA 100:6098-6103. 2003.
- Lu Y, Pan ZZ, Devaux Y, Ray P. PAK4 interacts with the keratinocyte growth factor receptor and participates in KGF-mediated inhibition of oxidant-induced cell death. J Biol Chem 278:10374-10380. 2003.
- Lu YB, Parkyn L, Otterbein LE, Kureishi Y, Walsh K, Ray A, Ray P. Activated Akt protects the lung from oxidant-induced injury and increases survival of mice. J Exp Med 193:545-549. 2001.
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Other
Links |
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University of Pittsburgh Division of Pulmonary, Allergy, and Critical Care Medicine
University of Pittsburgh |
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Office:
NW 628 MUH |
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Lab:
NW 648 MUH |
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Phone:
412.802.3192 |
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Fax:412.692.2260 |
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rayp@pitt.edu |
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Academic
Affiliations |
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- Associate Professor, Department of Medicine, University of Pittsburgh School of Medicine
- Associate Professor, Department of Immunology, University of Pittsburgh School of Medicine
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Education |
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- B.Sc. - Calucutta University (1977)
- M.Sc. - Calcutta University (1979)
- Ph.D. - Calcutta University (1985)
- Postdoc - Cornell University (1985-1987)
- Postdoc - Memorial Sloan-Kettering Institute (1987-1990)
- Associate Research Scientist, Yale University (1990-1991)
- Assistant Professor, Yale University (1992-1998)
- Associate Professor, Yale University (1998-2001)
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Grant
Support |
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- Title: KGF and Protection from Hyperoxic Lung Injury
Agency: NIH/NHLBI Role: P.I. Funding Period: 2005-2010
- Title: Chemokines and Immune Regulation in the Lung
Agency: NIH/NHLBI Role: P.I. Funding Period: 1998-2008
- Title: Mechanisms of Protection from Oxidative Lung Injury
Agency: NIH/NHLBI Role: P.I. Funding Period: 2003-2008
- Title: KGF and Inhibition of Pulmonary Fibrosis
Agency: NIH/NHLBI Role: P.I., Project 4 Funding Period: 2006-2011
- Title: Dendritic Cell-Epithelial Cell Interaction in CF Airway
Agency: NIH/NHLBI Role: P.I., Pilot Project in P30 Grant Funding Period: 2005-2007
- Title: DC-T Cell Interactions in Pulmonary Immune Response
Agency: NIH/NHLBI Role: Co-investigator Funding Period: 2004-2008
- Title: Mechanisms of Antigen Induced Tolerance in the Lung
Agency: NIH/NIAID Role: Co-Investigator Funding Period: 2006-2010
- Title: Th2 Differentiation and the GATA-3/T-BET Balance
Agency: NIH/NHLBI Role: Co-Investigator, Project 3 Funding Period: 2002-2007
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Lab
Personnel |
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Research Associates Meenakshi Arora, Ph.D. Li Chen, Ph.D. Rabindranath Ray, Ph.D.
Postdoctoral Fellow Jane Rose, Ph.D.
M.D./Ph.D. Student Nandini Krishnamoorthy
Research Specialists Manohar Yarlagadda Adam Henry Melissa Paglia |
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