Prabir Ray, Ph.D.
Contact
Office: NW 628 MUH
Lab: NW 648 MUH
Ph: 412-802-3192
Fax: 412-692-2260
Education
- B.Sc. - Calucutta University
- M.Sc. - Calcutta University
- Ph.D. - Calcutta University
- Postdoc - Cornell University
- Postdoc - Memorial Sloan-Kettering Cancer Center
Academic Affiliation
- UPMC Endowed Chair in Lung Immunology
- Professor, Department of Medicine
- Professor, Department of Immunology
About Research
My research is focused on understanding host defense mechanisms against respiratory pathogens. A primary goal is to establish strategies to prevent bacterial pneumonia in hospitalized patients. Gram-negative bacteria are common causes of pneumonia in critically ill and immunocompromised hospitalized patients which is associated with a high degree of morbidity and mortality worldwide. Pseudomonas aeruginosa, a ubiquitous Gram-negative bacterium, is a leading cause of ventilator-associated pneumonia (VAP) in critically ill patients. Despite access to new classes of antibiotics, multidrug resistance to P. aeruginosa has doubled over the past 30 years and there is an urgent need for alternative antibiotic-free approaches to combat this pathogen. In our ongoing studies, we have established a strategy to train the innate immune system to defend against a lethal infection by P. aeruginosa in a mouse model. Protective mechanisms involving training of neutrophils, revealed by scRNA-seq data, were validated in human ICU patients with acute respiratory failure that included those with a diagnosis of acute respiratory distress syndrome (ARDS). Our research has identified gene signatures in the peripheral blood that can discriminate between pneumonia patients who develop sepsis and advance to ARDS vs those who do not. Our research has also provided novel insights into cellular and molecular processes that help resolve inflammation and acute lung injury after bacterial pneumonia. Along these lines, our investigations led to the first identification of IL-10-expressing regulatory myeloid cells in the lung, resembling myeloid-derived suppressor cells (MDSCs), that play an important role in resolution of bacterial pneumonia. Another area of my investigation has involved host-pathogen interactions in the context of infection by respiratory syncytial virus (RSV). A highlight of this research was the demonstration of RSV infection in early life resulting in breaching of immune tolerance with promotion of an asthma phenotype in the host by disabling Tregs. This study was widely covered by both scientific and popular media worldwide including BBC news and other media. In related studies we have discovered the ability of the cytokine IL-22 to reduce viral titer in infected primary human airway epithelial cells and also in the lungs of newborn mice with cellular autophagy playing a role in the interplay between RSV and IL-22. I have continued collaboration with Dr. Anuradha Ray in studies of severe asthma which have recently shown a pathogenic role for IFN-g in a subset of steroid-refractory severe asthma patients identifying novel targets for therapy. We continue to successfully use both mouse models of infection using genetically altered mice and human data in combination with cutting-edge tools in immunology and molecular biology to address our research goals.
Selected Publications
Penaloza HF, Lee JS, Ray P (2021) Neutrophils and lymphopenia, an unknown axis in severe COVID-19 disease. PLoS Pathogens 17: e1009850.
Garg, M., Johri, S., Sagar, S., Mundhada, A., Agrawal, A., Ray, P., Chakraborty, K. (2021) Cardiolipin-mediated PPAR S112 phosphorylation impairs IL-10 production and inflammation-resolution during bacterial pneumonia. Cell Reports 34: 108736.
Jiang, Y., Rosborough, B.R., Chen, J., Das, S., Kitsios, G.D., McVerry, B.J., Mallampalli, R.K., Lee, J.S., Ray, A., Chen, W., Ray, P. (2020) Single cell RNA sequencing identifies an early monocyte gene signature in acute respiratory distress syndrome. JCI Insight 5: e135678.
Das, S., St.-Croix, C., Good, M., Chen, J., Zhao, J., Hu, S., Ross, M., Myerburg, M.M., Pilewski, J.M., Williams, J., Wenzel, S.E., Kolls, J.K., Ray, A., Ray, P. (2020) Interleukin-22 inhibits respiratory syncytial virus production by blocking virus-mediated subversion of cellular autophagy iScience 23:101256.
Das, S., Raundhal R., Chen J., Oriss, TB, Huff, R., Williams, JV, Ray, A, Ray P. (2017) Respiratory syncytial virus infection of newborn CX3CR1-deficent mice induces a pathogenic pulmonary innate immune response. JCI Insight 2 (17) e94605.
Chakraborty K., Raundhal M., Chen B.B., Morse C., Tyurina Y.Y., Khare A., Oriss T.B., Huff R., Lee J.S., St. Croix C.M., Watkins S., Mallampalli R.K., Kagan V.E., Ray A., and Ray P. (2017) The mito-damp cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia Nature Comm. 8: 13944.
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).
Ray A, Chakraborty K, Ray P. (2013) Immunosuppressive MDSCs induced by TLR signaling during infection and role in resolution of inflammation. Front Cell Infect Microbiol. 3:52.
Poe SL, Arora M, Oriss TB, Yarlagadda M, Isse K, Khare A, Levy DE, Lee JS, Mallampalli RK, Ray A*, Ray P.* (2013) STAT1-regulated Lung MDSC-like Cells Produce IL-10 and Efferocytose Apoptotic Neutrophils With Relevance In Resolution of Bacterial Pneumonia. Mucosal Immunol. 6:189-199 (*-co-senior author).
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). First study to show that a pathogen can target Tregs to impair immune tolerance.
Krishnamoorthy, N., Oriss, T.B., Paglia, M., Fei, M., Vanhaesebroeck, B., Ray, A. and Ray, P. (2008) 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 Med. 14: 565-573.
Ray, P., Devaux, Y., Stolz D.B., Yarlagadda, M., Watkins S.C, Liu, W., Lu, Y., Yang, X.F., Ray, A. (2003) Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia. Proc. Natl. Acad. Sci. USA, 100:6098-6103.
Lu, Y.B., Parkyn, L. Otterbein, L. E., Kureishi, Y., Walsh, K., Ray, A., Ray, P. (2001). Activated Akt protects the lung from oxidant-induced injury and increases survival of mice. J. Exp. Med. 193: 545-549.