Professor of Medicine and Immunology
Dr. Anuradha Ray received her Ph.D. from Calcutta University in India. She received postdoctoral training at Cornell University, Ithaca, NY and at Rockefeller University in New York. She was on the faculty at Rockefeller University and at Yale University between the years 1990 and 2001 before moving to the University of Pittsburgh. Dr. Ray serves as an Associate Editor for the journals Mucosal Immunology and the American Journal of Respiratory, Cell and Molecular Biology. She participates in multiple review panels of the NIH and other funding agencies. She previously served on the LBPA study section and is currently a member of the LCMI study section. She is an invited member of the Faculty of 1000 Biology in the Immunology discipline.
Dr. Ray’s overall research interest is to understand mechanisms of immune tolerance versus inflammation in the lung as they relate to pulmonary diseases such as severe asthma and host-pathogen interactions. Early research from her lab led to the identification of NF-kB as a target for glucocorticoid-mediated repression of gene expression and the discovery of GATA-3 as a master regulator of Th2 cells, which promote allergic diseases including asthma. Her laboratory also identified a key role for Tregs expressing membrane-bound TGF-b with cross-talk with the Notch pathway in promoting immune tolerance in the airways.
The primary goal of Dr. Ray’s current research is to understand interactions between dendritic cells (DCs) and T helper cells that either promote diseases such as asthma or suppress disease involving tolerogenic mechanisms. Ongoing work in her lab has identified an important role of mitochondrial metabolism in immune tolerance. Asthma is a heterogeneous disease with multiple sub-phenotypes. The most severe form of the disease poorly responds to standard therapy and is the least understood mechanistically. Recently, in a collaborative study between her lab and those of Drs. Sally Wenzel, Prabir Ray and Jay Kolls, an IFN-g/Th1 immune bias was demonstrated in the majority of severe asthmatics. This study also utilized a newly developed animal model of severe asthma established in her lab. The animal model can now be used to test novel therapeutics. This bedside-bench study has shown a detrimental role of IFN-g in downregulating expression of an important protease inhibitor, SLPI, in the airways of both humans and mice. In ongoing studies, her laboratory is also investigating the molecular mechanism underlying corticosteroid unresponsiveness in severe asthma. In the area of mucosal defense mechanisms against infectious agents, in collaborative studies between her lab and that of Dr. Prabir Ray, for the first time a pathogen, respiratory syncytial virus, was shown to disable Tregs in early life thereby compromising immune tolerance and increasing the risk for asthma in later life. Studies in her laboratory employ animal models of disease and human samples, which are analyzed using immunological, molecular, biochemical, physiological and imaging techniques. Her research has been continuously funded by multiple grants from the NIH.
Raundhal, M., Morse, M., Khare, A., Oriss, T.B., Milosevic, J., Trudeau, J., Huff, R., Pilewski, J., Holguin, F., Kolls, J. Wenzel, S.E., Ray, P., Ray, A. (2015) High IFN-g and Low SLPI Mark Severe Asthma In Humans and Mice. J. Clin. Invest. doi:10.1172/JCI80911. PMID: 26121748. -co-senior authors.
Khare, A., Chakraborty, K., Raundhal, M., Ray, P, Ray, A. (2015) Dual Function of PPARg in CD11c+ Cells Ensures Immune Tolerance in the Airways. Cutting edge: J Immunol. 195:431-435.
Oriss, T.B., Krishnamoorthy, N., Raundhal, M., Morse, C., Chakraborty, K., Khare, A., Huff, R., Ray, P., Ray, A. (2014) MMP-9 Inhibits IL-23p19 Expression in Dendritic Cells By Targeting Membrane Stem Cell Factor Affecting Lung IL-17 Response. Cutting Edge: J. Immunol. 192 5471-5.
Khare A., Krishnamoorthy, N., Oriss, T.B., Fei, M., Ray, P., Ray A. (2013) Inhaled Antigen Upregulates Retinaldehyde Dehydrogenase In Lung CD103+ But Not Plasmacytoid Dendritic Cells To Induce Foxp3 De Novo in CD4+ T cells and Promote Airway Tolerance. Cutting Edge: J. Immunol.191:25-29.
Krishnamoorthy, N., Khare, A.*, Oriss, T.B.*, Raundhal, M., Morse, C., Yarlagadda, M., Wenzel, S.E., Moore, M.L., Peebles, Jr., R.S., Ray, A., Ray, P, (2012) Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma Nature Med. (*equal contribution; co-senior authors) 18:1525-1530. Faculty of 1000 Biology Evaluation-Must Read (8). First study to show that a pathogen can target Tregs to impair immune tolerance.
Ray, A., A. Khare, N. Krishnamoorthy, and P. Ray. (2012). GATA-3. In Encyclopedia of Signalling Molecules. S. Choi, ed. Springer Philadelphia. pp. 760-769.
Fei, M., Bhatia S., Oriss, T.B., Yarlagadda, M., Khare, A., Akira, S., Saijo, S., Iwakura, Y., Fallert- Junecko, B.A., Reinhart, T., Foreman, O., Ray, P., Kolls, J.K., Ray, A. (2011) TNF-α From Inflammatory DCs Regulates Lung IL-17A/IL-5 Levels and Neutrophilia Versus Eosinophilia during Persistent Fungal Infection. Proc. Natl. Acad. Sci. USA 108:5360-5365.
Kreindler, J., Steele, C., Nguyen, N., Pilewski, J.M., Alcorn, J.F., Vyas, Y.M., Shean, A.J., Finelli, P., Blanchard, M., Zeigler, S.F., Logar, A., Hartigan, E., Kurs-Lasky, M., Rocketet, H., Ray, A., Kolls, J.K. (2010) Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis J. Clin. Invest. 120:3242-3254.
Ray A, Khare A, Krishnamoorthy N, Qi Z, and Ray P. (2010) Regulatory T cells in many flavors control asthma. Mucosal Immunol. 3:216-229.
Pillemer BB, Qi Z, Melgert B, Oriss TB, Ray P., Ray, A., (2009) STAT6 activation confers upon T helper cells resistance to suppression by regulatory T cells. J Immunol 183:155-163.
Krishnamoorthy N, Oriss TB, Paglia M, Fei M, Vanhaesebroeck B, Ray A, Ray P. Activation of the c-kit-PI3 kinase Axis Induces the Regulatory Cytokine Interleukin-6 in Dendritic cells Impacting Allergic Immune Responses In the Lung. Nature Medicine 2008; 14:565-573.
Ostroukhova M, Qi Z, Oriss TB, Dixon-McCarthy B, Ray P, Ray A. Treg-Mediated Immunosuppression Involves Activation of the Notch-HESI Axis By Membrane-bound TGF- b. J. Clin. Invest. 2006; 116:996-1004.
Oriss TB, Ostroukhova M, Seguin-Devaux C, Dixon-McCarthy B, Stolz DB, Watkins SC, Pillemer B, Ray P, Ray A. Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance. J. Immunol. 2005; 174: 854-863.
Ostroukhova M, Seguin-Devaux C, Oriss TB, Dixon-McCarthy B, Yang L, Ameredes B, Corcoran TE, Ray A. Tolerance Induced by Inhaled Antigen Involves CD4+ T Cells Expressing Membrane-Bound TGF-v and FOXP3. J. Clin. Invest. 2004; 114:28-38.
Dr. Ray is featured in many articles, including those below: