University of Pennsylvania, Philadelphia, USA
Royal Postgraduate Medical School, London, UK
National Institutes of Health, Bethesda, USA
Analysis of innate and adaptive immune responses.
Lucas D’Souza, Srijani Basu, Snehlata Gupta, Suman Gupta, Aashima Rao
Summary of Research
The broad aim of research efforts in my laboratory is to track the generation and maintenance of immune responses following infection or immunization and to study the nature of microbial homeostasis and its disruption in the gut. The laboratory works in close collaboration with Dr Vineeta Bal and Dr. Satyajit Rath. With the help of molecular, biochemical and cellular in vitro approaches, as well as classical in vivo approaches, we are currently:
- Identifying signals that control B cell differentiation. We have shown that signaling through the TNF receptors CD27 and CD40 during B cell activation inhibits the generation of antibody secreting plasma cells while enhancing the generation of memory cells. We are currently probing the effect of homeostatic ligation of CD40 in influencing cell fate determination.
- Assessing factors that influence plasma cell longevity. We have shown recently that nitric oxide is involved in signaling pathways that affect the survival of plasma cells in spleen and bone marrow. We are currently attempting to determine if it is also involved in the survival of autoreaactive plasma cells.
- Trying to identify adjuvants that will facilitate an IgAresponse following subcutaneous immunization. The idea is to cirvumvent problems associated with oral immunization, such as poor absorption, lack of oral adjuvants and the difficulty of boosting by this route
- Looking at how the diversity of intestinal microflora is influenced by the absence of specific cytokines and other molecules, and whether this correlates with differential levels of basal B cell stimulation in vivo.
- Satpathy S, Shenoy GN, Kaw S, Vaidya T, Bal V, Rath S and George A (2010) Inhibition of terminal differentiation of B cells mediated by CD27 and CD40 involves signalling through JNK. J Immuol. 185:6499-6507.
- Varanasi V, Mattoo H, Tupperwar NC, Thyagarajan K, Das A, Kumar R, Bal V, Vaidya T, George A, Rath S (2010) A superantigen interacts with leishmanial infection in antigen-presenting cells to regulate cytokine commitment of responding CD4 T cells. J Infect Dis 202:1234-45.
- Khare A, Viswanathan B, Gund R, Jain N, Ravindran B, George A, Rath S, Bal V (2011) Role of Bruton's tyrosine kinase in macrophage apoptosis. Apoptosis 16:334-346.
- Chatterjee P, Tiwari RK, Rath S, Bal V, George A (2012). Modulation of antigen presentation and BCR signaling in B cells of beige mice. J Immunol. 188:2695-2702.
- Shenoy GN, Chatterjee P, Kaw S, Mukherjee S, Rathore DK, Bal V, Rath S, George A (2012). Recruitment of memory B cells to lymph nodes remote from the site of immunization requires an inflammatory stimulus. J. Immunol 189: 521-528.
- Panda SK, Kumar S, Tupperwar NC, Vaidya T, George A, Rath S, Bal V, Ravindran B (2012). Chitohexaose actiates macrophages by alternate pathway through TLR4 and blocks endotoxemia. Plos Pathogens 8(5): e1002717.
- Banerjee H, Das A, Srivastava S, Mattoo HR, Thyagarajan K, Khalsa JK, Tanwar S, Das DS, Majumdar SS, George A, Bal V, Durdik JM, Rath S (2012) A role for apoptosis-inducing factor (Aif) in T cell development. J Exp Med. 209:1641-53.
- Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, Saini H, Kotresh ST, Ali U, Bhatia D, Ohri A, Kumar M, Agarwal I, Gulati S, Anand K, Vijayakumar M, Sinha R, Sethi S, Salmona M, George A, Bal V, Singh G, Dinda AK, Hari P, Rath S, Dragon-Durey MA, Bagga A (2013) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int. 85:1151-1160.
- Saini AS, Shenoy GN, Rath S, Bal V, George A (2014) Inducible nitric oxide synthase is a major intermediate in signaling pathways for plasma cell survival. Nat Immunol 15: 275-282.
- Upadhyay M, Krishna Priya G, Ramesh P, Madhavi MB, Rath S, Ba; V, George A, Vaidya T (2014)CD40 signaling drives B lymphocytes into a memory-like state that is intermediate between naïve cells and plasma cells. J. Cell Physiol. 229: 1387-1396.
- Rane S, Das R, Ranganathan V, Prabhu S, Das A, Mattoo H, Durdik JM, George A, Rath S, Bal V (2014) Peripheral residence of naïve CD4 T cells induces MHC class II-dependent alterations in phenotype and function. BMC Biology 12: 106.