In a multidisciplinary research program, we are using systems biology tools to characterize regulatory cell circuitries that enable crosstalk between various immune activating and homeostatic signals.In sum, we are interested in understanding physiological and patho-physiological consequences of such cross-regulations in the context of
i) Inflammatory immune response and inflammatory diseases
ii) Neoplastic disorders
Summary of Research:
A multitude of biochemical processes links the intracellular signaling pathways in a network. Importantly, this interlinked signaling network, and not the individual pathways, eventually shapes cellular responses. Because of the complexity of the signaling network, assigning specific interactions between signaling modules to distinct immune functions has remained challenging.Our research interest lies in exploring the crosstalk between these “dedicated” signaling pathways and understanding the implications of such interdependent regulations in physiology and patho-physiology.
In particular, the NF-kappaB system has the remarkable capacity to process signals from a variety of extracellular as well as intracellular cues, those include pathogen derived substances, host-derived cytokines, cell-differentiating and developmental cues, reactive oxygen species or metabolic substances.The NF-κB systemtransduces these signals through either the canonical or the non-canonical module to activate an overlapping set of close to a dozen of transcription factors.In our laboratory, we have considered this pleiotropic NF-κB systemas a potential playerin mediating signaling crosstalk in varied physiological context. In a multidisciplinary research program that combines biochemistry, molecular biology, cell biology, mouse genetics and computational modeling, we aim to biochemically characterize the cross-regulatory elementsembedded within the NF-κB system that enable crosstalk between immune activating and homeostatic cues. By simulating a computational model describing the NF-κB system, we generatein silico predictions on pathway crosstalks. Using biochemical assays, such as Immunoblot analysis, EMSA, Real Time PCR etc., and genetic tools, including a panel of knockout cells,we then test signaling crosstalk ex vivo. Finally, we examine potential physiological or pathophysiological ramification of pathway crosstalks in vivo in murine model.One long-term objective of our research program is to eventually define connectivities between the NF-κB system and other important immunesignaling pathways, such as type-1 IFN pathway.
Our systems based approach not only promises new mechanistic insights into the dynamic control of immune responses but also has therapeutic importance. Our finding bears promises for disease-specific interventions in inflammation-associated diseases that target the crosstalk motif delinking inflammatory module from the integrated network.
Yashika Ratra, Uday Aditya Sarkar, Manti Kumar Saha, Alvina Deka, Naveen Kumar, Chandrima Bharadwaj, Shivani Rajoriya and Gayathri Devi, (Ph.D. students); Syed Yusuf Mian (Research Associate); Birendra Kumar and Vijendra Kumar (Technical help)
• 2021 : Elected Fellow of the Indian Academy of Sciences (IASc).
• 2021 : Elected Fellow of the National Academy of Science India (NASI).
• 2019 : Shanti Swarup Bhatnagar Award for Research Excellence in Biological Sciences.
• 2018 : Received the National Bioscience Award for Career Development in recognition of the research in the area of immunology and cell signaling.
• 2017 : Elected as a member of the Guha Research Conference.
• 2010-2015 : Intermediate Fellowship, Wellcome Trust-DBT India Alliance.
• 2010 : Ramachandran fellowship, National Institute of Immunology, Department of Biotechnology, India.
• 2003 : Young Scientist Award from the Indian Science Congress Association (ISCA).
James Gomes and Manidipa Banerjee from IIT-Delhi, Shailly Tomar from IIT-Roorkee, Guruprasad R. Medigeshi from THSTI-Faridabad, Sunil K. Raghav from ILS-Bhubaneswar, Abhyudai Singh from Univ. of Delaware,Vineet Ahuja from AIIMS, and Subhra K. Biswas from Singapore.