Anuradha Ray, Ph.D.
Office: NW 628 MUH
Lab: NW 628 MUH
- B.Sc. - Calcutta University
- M.Sc. - Calcutta University
- Ph.D. - Calcutta University
- Postdoc - Cornell University
- Postdoc - Rockefeller University
- UPMC Endowed Chair in Lung Immunology in Medicine
- Professor, Department of Immunology, University of Pittsburgh School of Medicine (2002-to date)
- Visiting Professor, Department of Medicine, University of Pittsburgh School of Medicine (2001-2002)
- Assistant Professor, Yale University (1992-1997)
- Assistant Professor, Rockefeller University (1990-1991)
Over the years, Dr. Ray has pursued two main areas of research. In one, she has studied immune responses elicited in the airways by allergens and pathogens to understand the immunological and molecular basis of inflammatory diseases like asthma. In the second, she has investigated mechanisms that counter inflammation. Dr. Ray's early research showed for the first time that corticosteroids suppress inflammation not via DNA-binding of the glucocorticoid receptor (GR) to promoters of target pro-inflammatory genes, which was then the prevailing theory of steroidmediated regulation of gene transcription, but by direct protein-protein interactions between GR and the transactivator NF-kB rendering it unavailable for transcriptional activation. In studies of the immunological underpinnings of asthma, her work led to the discovery of GATA-3 as an essential regulator of Th2 cells, which promote asthma and allergic diseases. More recently, her studies have shown that corticosteroid-refractory severe asthma involves a more complex immune response with Th1 dominance in many patients. On the flip side, to understand how the pulmonary immune system maintains immune homeostasis or tolerance despite constant provocation by environmental antigens, her work identified an important role of Tregs in preventing unwarranted airway inflammation. The primary goal of Dr. Ray’s current research is to unravel the heterogeneity in immune networking in both severe and milder asthma to allow better therapeutic management of disease. In this context, ongoing work in her laboratory is focused on dendritic cell-T cell interactions as they relate to diseases like severe asthma or to immune tolerance to prevent such diseases using both human samples and animal models. She is also interested in mechanisms by which pathogens subvert the immune system. Dr. Ray is an invited member of the Faculty of 1000 Biology in the Immunology discipline. Her research has been continuously funded by multiple grants from the National Institutes of Health.
Links: BBC News and Pittsburgh Post-Gazette
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. 125:3037-3050. PMID: 26121748. ¶,-co-senior authors. Highlighted in Nature Revs. Immunol and Sci. Transl. Med.
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. PMID: 26062999.
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 5471-5475. PMCID: PMC4063408 [Available 2015/6/15].
Voraphani N, Gladwin, MT, Contrerars AU, Kaminski N, Tedrwo JR, Milosevic J, Bleecker ER, Meyers DA, Ray A, Ray P, Erzurum SC, Busse WW, Zhao J, Trudeau JB, Wenzel, SE (2014) An airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma. Mucosal Immunol. 7: 1175-85. PMCID: PMC4130801
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.
Krishnamoorthy, N., Oriss, T.B., Paglia, M., Fei, M., Vanhaesebroeck, B., Ray, A*. and Ray, P.* (2008) Activation of the c-kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Nature Med. 14: 565-573 (*-co-senior author)
Xu, H Oriss, T.B., Fei M, Henry A.C., Melgert, B.N., Chen, L, Mellor A.L, Munn, D.H., Irvin, C.G., Ray, P., Ray, A. (2008) Indoleamine 2,3-Dioxygenase in the Lung Dendritic Cells Promotes Th2 Responses and Allergic Inflammation. Proc Natl Acad Sci USA 105: 6690-6695.
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 116:996-1004. 2006.
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-b and FOXP3. J Clin Invest 114:28-38. 2004.
Chen C-H, Devaux CS, Burke NA, Oriss TB, Watkins SC, Clipstone N, Ray A. Transforming Growth Factor-B blocks Tec kinase phosphorylation, Ca2+ influx and NFATc translocation causing inhibition Of T cell differentiation. J Exp Med 197:1689-1699. 2003.
Das J, Chen C-H, Yang L, Cohn L, Ray P, Ray A. A critical role of NF-KB in GATA-3 gene expression and Th2 differentiation in allergic airway inflammation. Nature Immunol 2:45-50. 2001.
Zhang, D. -H., Yang, L., Cohn, L., Parkyn, L., Homer, R., Ray, P., Ray, A. (1999) Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity, 11: 473-482.