Calcutta University, Kolkata, India
Calcutta University, Kolkata, India
University of California, San Diego, USA
In a multidisciplinary research program, we aim to characterize regulatory circuitries that enable crosstalk between various immune activating and homeostatic cues using systems biology tools.In sum, we are interested in understanding physiological and patho-physiological consequences of such cross-regulations in the context of
i) bacterial pathogenesis
ii) neoplastic disorders
iii) cell differentiation and tissue and organ development
iv) viral immunity
Dr. Rakesh Pandey, PhD, DST Inspire Fellow;
Payel Roy, Tapas Mukherjee, Budhaditya Chatterjee, Sachendra Singh Bais, Meenakshi Chawla, Ankita Dabla, Yashika Ratra, Uday Aditya Sarkar (PhD student);
Vijendra Kumar (Laboratory Technician);
Summary of Research
Mammalian cells receive and process signals from a variety of extra-cellular stimuli those engage “dedicated” signaling pathways to elicit appropriate cellular responses. In physiological settings, however, a variety of different stimuli are often impinged upon a single cell simultaneously activating multiple signaling pathways; thereby generatingthe possibility for crosstalk between these apparently insulated cell-signaling pathways. Our research interest lies in exploring the interplay between these “dedicated” signaling pathways and understanding the implications of such interdependent regulations in physiology and patho-physiology.
In particular, the NF-kappaB signaling 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-kappaB system receives signals through either the canonical or the non-canonical arms to potentially activate a dozen of transcription factors. In our laboratory, we have considered the pleiotropic NF-kB 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 mathematical modeling, we aim to identify and characterize the crossregulatory elements embedded within the NF-kB system that enable crosstalk between immune activating and homeostatic cues. By simulating a computational model, we are generating conceptual framework in silicoon plausible crosstalk regulations. Using biochemical assays, such as Immunoblot analysis, EMSA, Real Time PCR etc., and genetic tools, including a panel of knockout cells,we are testing signaling crosstalk ex vivo. Finally, we are examining 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-kB system and other important immune pathways, such as type-1 IFN system.
Our systems based approach not only promises new mechanistic insights into the dynamic control of immune responses but also has therapeutic importance. Targeting the proposed crosstalk components in inflammatory diseases and in pathogenesis bears the promise to reduce the devastating side effects that are often associated with the treatment regimes that target signaling hub molecules.
Awards / Fellowships
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.
- Chatterjee B, Banoth B, Mukherjee T, Taye N, Vijayaragavan B, Chattopadhyay S, Gomes J, Basak S; Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages. Sci Signal. 2016 Dec 6;9(457):ra120.
- Roy P, Mukherjee T, Chatterjee B, Vijayaragavan B, Banoth B, Basak S; Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50NFκB pathway. Oncogene. 2016 Sep 19.
- Jain N, Khullar B, Oswal N, Banoth B, Joshi P, Ravindran B, Panda S, Basak S, George A, Rath S, Bal V, Sopory S; TLR-mediated albuminuria needs TNFα-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice. Dis Model Mech. 2016 Jun 1;9(6):707-17.
- Rachel Tsui, Jeff Kearns, Candace Lynch, Don Vu, Kim Ngo, Soumen Basak, Gourisankar Ghosh, Alexander Hoffmann; The Rel-NFκB dimer generation module: monomer competition and a function for IκBβ. Nature Communication, 2015 May7;6:7068.
- Balaji Banoth, Bharath Vijayaragavan, Budhaditya Chatterjee, M.V. R. Prasad, Payel Roy, Soumen Basak; Developmental LTbR reinforces TLR4 triggered inflammatory RelA/NF-kappaB responses to ameliorate the pathogen clearance in the gut. eLife, 2015 May 15. http://elifesciences.org/content/4/e05648
- Almaden JV, Tsui R, Liu YC, Birnbaum H, Shokhirev MN, Ngo KA, Davis-Turak JC, Otero D, Basak S, Rickert RC, Hoffmann A. A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells. Cell Reports, 2014 Dec 24;9(6):2098-111.
- Soumen Basak, Marcelo Behar, Alexander Hoffmann: Lessons from modeling the NF-κB pathway. Immunological Reviews, 2012,Mar; 246(1):221-38.
- Abraham S., Nagaraj AS.,Basak S., and Manjunath R; Japanese encephalitis virus utilizes the canonical pathway to activate NF-κB but type I interferon pathway to induce MHC-I expression. J Virol. 2010 Jun;84(11):5485-93.
- Soumen Basak*, ArindamMondal, SmarajitPolley, SubhradipMukhopadyay and Dhrubajyoti Chattopadhyay*;Reviewing Chandipura: A vesiculovirus in human epidemics. Bioscience Reports, 27(4-5): 275-98, Oct 2007.