Dr. Soumen Basak

A multitude of biochemical processes links the intracellular signaling pathways in a network. 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. Implementing a systems biology-based approach, we are exploring the crosstalk between these “dedicated” signaling pathways and understanding the implications of such interdependent regulations in physiology and pathophysiology. In particular, we are exploring if such crosstalks have functional relevance for
i) inflammation and inflammation-associated ailments, and ii) for anti-viral immunity.
I. Inflammation and Inflammation-associated diseases: Microbial substances engage the canonical RelA NF-kB pathway, which triggers the expression of dozens of pro-inflammatory cytokines and chemokines. While controlled canonical signaling is important for physiological inflammatory innate immune responses, excessive RelA activity leads to inflammatory ailments. Importantly, a seemingly separate non-canonical RelB NF-kB pathway mediates the development and maturation of secondary lymphoid organs organs and lymphocytes. In this program, we are specifically testing if crosstalk between these NF-kB pathways and those involving Wnt-b-catenin signaling act as an inflammation-tuning immunoregulatory mechanism. We are also investigating if aberrant pathway crosstalk causes inflammatory diseases, particularly inflammatory bowel diseases (IBD) and colorectal cancer (CAC). In a systems-modeling approach, we are combining in silico studies involving a computational model trained to capture inflammatory signaling dynamics and ex vivo biochemical analyses involving a panel of knockout cells devoid of the expression of one or the other signaling proteins to understand crosstalk regulations of inflammatory responses. Mechanistic insights from such studies are then substantiated in vivo in mouse models of IBD and CAC involving cell-type specific knockout mice. Our systems based approach not only promises new mechanistic insights into the dynamic control of inflammatory responses but also bears promises for disease-specific interventions in inflammation-associated diseases that target crossregulatory signaling mechanisms.
II. Antiviral immune responses: Besides canonical RelA NF-kB signaling, viral infections also trigger the IRF3 signaling axis. In particular, RelA plays two important antiviral functions. First, RelA-driven expression of cytokines and chemokines instructs CD8+ T cell engagement during viral pathogenesis. In collaboration with IRF3, RelA also activates genes encoding type-1 interferons, a family of antiviral mediators. However, by inducing pro-survival gene expressions, RelA extends the life span of virus-infected cells, supporting overall viral yield. On the other hand, the non-canonical RelB NF-kB pathway downmodulates type-1 interferon responses elicited by infected cells while restricting virus propagation in vivo by virtue of its ability to orchestrate secondary lymph node functions. In this program, we are addressing how these often opposing roles of intracellular pathways interface in defining antiviral immunity. In particular, we are focusing on two important viruses of human health relevance – namely, Chandipura virus, a virus often associated with encephalitis outbreaks in India, and Chikungunya virus, a continuing global threat, particularly in the context of climate change. Combining ex vivo cell signaling studies and mouse models for viral infection, we are addressing how cell-signaling crosstalks impact viral pathogenesis. We hope that our study will inform novel antiviral therapies in the future.

Awards:
• 2023: Incorporated as a member of the Society of Inflammation Research, India
• 2022: Elected as a Fellow of the Indian National Science Academy (INSA, New Delhi)
• 2021: Elected Fellow of the Indian Academy of Sciences (IASc, Bangalore)
• 2021: Elected Fellow of the National Academy of Sciences India (NASI, Prayagraj)
• 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 Fellow, Wellcome Trust-DBT India Alliance
• 2003: Young Scientist Award from the Indian Science Congress Association (ISCA)

Collaborators:
Aneeshkumar G., Sangeeta Bhaskar, NII-New Delhi; Alexander Hoffmann, Univ. of California, Los Angeles; Abhyudai Singh, Univ. of Delware; Guruprasad R. Medigeshi, Amit Awasthi and Bhabatosh Das, THSTI-Faridabad; James Gomes and Manidipa Banerjee, IIT- Delhi; Vineet Ahuja from AIIMS; Shilpak Chatterjee IICB-Kolkata; Rajesh Gokhale, IISER-Pune.