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Anuradha Ray Ph.D.

  • UPMC Endowed Chair in Lung Immunology in Medicine
  • Professor, Department of Medicine
  • Professor, Department of Immunology
  • PMI Graduate Faculty

    Education & Training

  • Postdoc - Rockefeller University
  • Postdoc - Cornell University
  • Ph.D. - Calcutta University
  • M.Sc. - Calcutta University
  • B.Sc. - Calcutta University
Representative Publications

Ray A, Das J, Wenzel SE (2022) Determining Asthma Endotypes and Outcomes: Complementing Existing Clinical Practice with Modern Machine Learning Cell Reports Medicine (invited article published in special issue on Artificial Intelligence in Medicine) 3:100857. 

Yuan H, Chen J, Hu S, Oriss TB, Kale S, Das S, Nouraie SM, Ray P, Ray A (2022) Early life exposure to house dust mite allergen prevents experimental allergic asthma requiring mitochondrial H2O2. Mucosal Immunol. 15: 154-164. 

Camiolo MJ, Zhou X, Oriss TB, Yan Q, Gorry M, Horne W, Trudeau J, Scholl K, Chen W, Kolls JK, Ray P, Weisel FJ, Weisel NM, Aghaeepour N, Nadeau K, Wenzel SE, Ray A (2021) High dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status. Cell Reports 35:108974. 

Gauthier M, Chakraborty K, Oriss TB, Raundhal M, Das S, Chen J, Huff R, Sinha A, Fajt M, Ray P, Wenzel SE, Ray A (2017) Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias. (2017) JCI Insight 2. e: 94580.   

Oriss TB, Raundhal M, Morse C, Huff RE, Das, Hannum R, Gauthier MC, Scholl KL, Chakraborty K, Nouraie SM, Wenzel SE Ray P, Ray A. IRF5 distinguishes severe asthma in humans and rives Th1 phenotype and airway hyperreactivity in mice (2017) JCI Insight 2, e:91019. 

Khare A, Raundhal M, Chakraborty K, Das S, Corey C, Kamga CK, Quesnelle K, St. Croix C, Watkins SC, Morse C, Oriss TB, Huff R, Hannum R, Ray P, Shiva S, Ray A. (2016) Mitochondrial H2O2 in lung antigen-presenting cells blocks NF-kB activation to block unwarranted immune activation. Cell Reports 15:1700-1714. 

Raundhal M, Morse M, Khare A, Oriss TB, Milosevic J, Trudeau J, Huff R, Pilewski J, Holguin F, Kolls J, Wenzel SE, Ray P¶,*, Ray A.¶,* (2015) High IFN-g and Low  SLPI Mark Severe Asthma In Humans and Mice. J. Clin. Invest. 125:3037-3050. (*equal contribution; *co-senior authors). 

Krishnamoorthy N, Khare A.*, Oriss TB*, Raundhal M, Morse C, Yarlagadda M, Wenzel SE, Moore ML, Peebles Jr, RS, Ray A,¶,* Ray P.¶,* (2012) Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma Nature Med 18:1525-1530. (*equal contribution; *co-senior authors)  

Fei M, Bhatia S, Oriss TB, Yarlagadda M, Khare A, Akira S, Saijo S, Iwakura Y, Fallert- Junecko BA, Reinhart T, Foreman O, Ray P, Kolls JK, 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. 

Ostroukhova M, Qi Z, Oriss TB, Dixon-McCarthy B, Ray P, Ray A. (2006) T Regulatory Cell-Mediated Immunosuppression Involves Activation of the Notch-HESI Axis By Membrane-bound TGF-b. J. Clin. Invest. 116:996-1004.  

Das J, Chen C -H, Yang L, Cohn L, Ray P, Ray A. (2001) A critical role of NF-B in GATA-3 gene expression and Th2 differentiation in allergic airway inflammation. Nature Immunol. 2:45-50. 

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. 

Research Interests

My research centers around the opposite ends of the immune spectrum-one that maintains immune tolerance in the airways to prevent the development of asthma and the other that causes immune dysfunction in asthma which can manifest as severe, corticosteroid-refractory poorly managed disease. I am also interested in mucosal defense mechanisms against infectious agents. Research from my laboratory was the first to identify a central mechanism by which corticosteroids inhibit inflammation by interactions of the glucocorticoid receptor with the transcription factor NF-κB. Work from my laboratory first identified the transcription factor GATA-3 as the master regulator of Th2 cells, which play an integral role in asthma pathogenesis. Subsequently, GATA-3 was successfully targeted in mild allergen-induced asthma (NEJM, 2015). However, as has become evident in recent years, asthma is a complex, heterogeneous disease and cannot be solely explained by a heightened Th2 immune response. Along these lines, using human data and mouse models, we have shown a prominent role for Type 1 immunity/IFN-g-producing T cells, normally associated with autoimmunity, often mixed with Type 2 immunity, in promoting severe asthma in a subset of asthmatics. Using advanced tools of immunology such as mass cytometry, high dimensional flow cytometry and RNA-seq approaches we described for the first time a heterogeneous immune profile in the airways of asthmatics divided along the lines of innate and adaptive immunity never described before. This publication was featured in a press release by the NIH on World Asthma Day on May 5, 2021. Our most recent work has revealed the CCL5-CCR5 axis as a bridge between T1 and T2 immunity in severe asthma suggesting CCR5 as a novel target for therapy for the sickest of asthma patients. Our asthma work is supported by a multi-PI P01 grant with Dr. Sally Wenzel with whom I have collaborated for >10 years to study immune dysfunction in severe asthma. In studies of immune tolerance in the airways, we identified a role for membrane-bound TGF-b on Tregs with cross-talk with Notch as an underlying mechanism. In addition, we have implicated mitochondrial H2O2 in dendritic cells (DCs) as a regulator of immune tolerance. Ongoing studies show a novel mechanism by which mitochondrial H2O2 impacts DC migration to draining lymph nodes as well as their survival. As suggested by analysis of available scRNA-seq data from human airways of asthmatics, this pathway may also underlie development of asthma in humans. I also have a long-standing collaboration with Dr. Prabir Ray on his studies of host-pathogen interactions.