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-?B 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-ß with cross-talk with Notch in promoting immune tolerance in the airways.
The primary goal of Dr. Ray’s current research is to understand the immunological and molecular differences between severe and milder asthma and the mechanisms underlying poor response to corticosteroids in severe disease. A study published recently by her group has demonstrated an
IFN-?/Th1 immune bias in more than 50% of severe asthmatics. This study also utilized a newly developed animal model of severe asthma established in her lab, which can be used to test novel therapeutics for severe asthma. This bedside-bench study identified a detrimental role of IFN-? in downregulating expression of the protease inhibitor, SLPI, in the airways of both humans and mice. In the context of immune tolerance, her recently published study has identified an important role of mitochondrial metabolism in lung dendritic cells in the maintenance of immune tolerance in the airways. Studies in her laboratory employ animal models of disease and human samples, which are analyzed using immunological, molecular, biochemical, physiological and imaging techniques.
- BSc, Chemistry, Calcutta University, 1976
- MSc, Biochemistry, Calcutta University, 1978
- PhD, Molecular Biology, Calcutta University, 1984
- Postdoctoral Fellowship, Cornell University, 1986
- Postdoctoral Associate, The Rockefeller University, 1988
Education & Training
Khare, A., Raundhal, M., Chakraborty, K., Das, S., Corey, C., Kamga, C.K., Quesnelle, K., St. Croix, C., Watkins, S.C., Morse, C., Oriss, T.B., Huff, R., Hannum, R., Ray, P., Shiva, S., Ray, A. Mitochondrial H2O2 in lung antigen-presenting cells blocks NF-kappaB activation to block unwarranted immune activation. Cell Reports. 2016; 15: 1700-1714.
Ray, A., Prefontaine, K.E. Physical association and functional antagonism between the p65 subunit of NF-kappaB and the glucocorticoid receptor. Proceedings of the National Academic Science of the United States of America. 1994; 91: 752-756.
Zang, D.-H,, Cohn, L., Ray, P, Bottomly, K., Ray, A. Transcription factor GATA-3 is differentially expressed in Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. Journal of Biological Chemistry. 1997; 272: 21597-21603.
Zhang, D.-H., Yang, L., Cohn, L., Parkyn, L., Homer, R., Ray, P., Ray, A. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity. 1999; 11: 473-482.
Das, J., Chen, C.-H, Yang, L., Cohn, L., Ray, P., Ray, A. A critical role of NF-kappaB in GATA-3 gene expression and Th2 differentiation in allergic airway inflammation. Nature Immunology. 2001; 2: 45-50.
Ostroukhova, M., Sequin-Devaux, C., Oriss, T.B., Dixon-McCarthy, B., Yang, L., Ameredes, B., Corcoran, T.E., Rray, A. Tolerance Induced by Inhaled Antigen Involves CD4+ T Cells Expressing Membrane-Bound TGF-Beta and FOXP3. Journal of Clinical Investigation. 2004; 114: 28-38.
Ostroukhova, M., Qi, Z., Oriss, T.B., Dixon-McCarthy, B., Ray, P., Ray, A. T Regulatory Cell-Mediated Immunosuppression Involves Activation of the Notch-HESI Axis By Membrane-bound TGF-Beta. Journal of Clinical Investigation. 2006; 116: 996-1004.
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. TNF-alpha From Inflammatory DCs Regulates Lung IL-17A/IL-5 Levels and Neutrophilia Versus Eosinophilia during Persistent Fungal Infection. Proceedings of the National Academy of Science in the United States of America. 2011; 108: 5360-5365.
Krishnamoorthy, N., Khare, A., Ooriss, T.B., Raundhal, M., Morse, C., Yarlagadda, M., Wenzel, S.E., Moore, M.L., Peebles, R. S., Ray, A., Ray, P. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nature Medicine. 2012; 18: 1525-1530.
Raundhaal, M., Morsse, M., Khare, A., Oriss, T.B., Milosevic, J., Trudeau, J., Huff, R., Pilewski, J., Holguin, F., Kolls, J., Wensel, S.E., Ray, P., Ray, A. High IFN-? and Low SLPI Mark Severe Asthma In Humans and Mice. Journal of Clinical Investigation. 2015; 125: 3037-050.
- Member -Lung Biology and Pathology (LBPA) Study Section, 1999-2003
- Elected member of Faculty of 1000 Biology in Immunology Discipline, 2004
- Appointed Member of University Research Council,, 2006-2009
- Associate Editor, Mucosal Immunology, 2010-
- Member “Board of Scientific Counselors” to review NIAID Intramural Programs in Immunology, 2012
- Member, NIH LCMI study section, 2012-2016
- Joseph S. Ingraham Immunology Lecturer for 2013, The Department of Microbiology and Immunology at Indiana University School of Medicine, 2013
- Invited by Merck & Co., Inc. as Immunology training lecturer in preparation for launching of their new immunotherapy initiative, 2013
- Associate Editor, American Journal of Respiratory, Cell and Molecular Biology, 2013
- American Thoracic Society’s Recognition Award for Scientific Accomplishments, 2016
