Department of Medicine
University of Pittsburgh
Anuradha Ray, PhD
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Professor of Medicine and Immunology Phone: 412-692-2211 |
Bio
Dr. Anuradha Ray received her Ph.D. from Calcutta University in India. She underwent 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.
Academic and Research Interests
The primary goal of Dr. Ray’s research is to understand immune mechanisms involving interactions between dendritic cells (DCs), T helper cells and T regulatory cells as they relate to the regulation of chronic inflammatory diseases in the lung and the gut such as asthma and inflammatory bowel disease. She is also interested in mucosal defense mechanisms against infectious agents. Her key contributions in these areas include: 1) Identification of NF-kB as a target for the anti-inflammatory actions of corticosteroids (PNAS 91:752, 1994), 2) Discovery of GATA-3 as the master transcriptional regulator of Th2 cells (JBC 272: 21597; Immunity 11:473, 1999; Nature Immunol. 2:45, 2001) and its expression in human disease (JACI 103:215, 1999). 3) The role of membrane-bound TGF-b on Tregs in the induction of airway tolerance to allergens and cross-talk between TGF-b and Notch as the underlying mechanism (JCI 114:28, 2004; JCI 116:996, 2006). 4) The c-kit-IL-6 axis in DCs promoting Th2 and Th17 responses and allergic asthma (co-senior author with Prabir Ray-Nature Medicine 14:565, 2008). All studies in her laboratory employ genetically altered mice and various immunological, molecular, biochemical and imaging techniques.
Her research has been continuously funded by multiple grants from the NIH. Currently, she is Principal Investigator on 3 grants, 2 RO1s and a SCCOR grant Project and is also a co-investigator on additional grants. She was invited to be a member of the Faculty of 1000 Biology in the Immunology discipline.
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In this study, we showed that the ratio of the 2 subsets of dendritic cells, plasmacytoid (pDC) and myeloid (mDC), flips in the lung-draining lymph nodes of mice under conditions of immune tolerance, when mice are exposed to antigen (OVA) alone, versus inflammation when mice are exposed to both antigen and cholera toxin (CT-a mucosal adjuvant). In other literature, pDCs have been predominantly associated with immune tolerance (exceptions include viral infections) while mDCs promote inflammation (exceptions include CD8a+ splenic DCs that induce apoptosis of CD4 T cells). |
Tregs expressing membrane-bound TGF-b (TGF-bm+ Tregs) are induced when mice are tolerized with inhaled antigen. These Tregs isolated from tolerized mice are potent suppressors of the asthma phenotype when transferred to recipient mice (Ostroukhova et al., JCI 114:28, 2004). The mechanism of suppression involves activation of Notch in target T helper cells. Thus, TGF-bm+ Tregs lose their suppressive function when transferred together with neutralizing aNotch1 Ab. |
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The enzyme indoleamine 2,3 dioxygenase (IDO) has been predominantly associated with immunesuppression in the literature. Our study showed that IDO does not cause immunesuppression in the context of allergen exposure but instead is actually required to induce optimal allergic airways disease (asthma) in an experimental model in the mouse. IDO deficiency resulted in accumulation of fewer mature myeloid DCs in the lung-draining LNs of mice. Consequently, fewer cytokine-producing cells were recovered from the lungs of IDO-/- mice. The mice displayed less mucus production and less airway hyperresponsiveness in a chronic model of the disease. |
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Key Publications
Xu H, Oriss TB, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. Indoleamine 2,3-Dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation but is not required for tolerance. Proc.Natl. Acad. Sci. USA 2008; 105:6690-6695.
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.
PubMed Link
News
Dr. Ray is featured in many articles, including those below: