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Roshan J. Thapa, MD
Assistant Professor
Baruch S. Blumberg Institute of Living Science
MD, Manipal College of Medical Sciences (Nepal)

Mailing Address:
Doylestown , PA

Research Interests

Currently, Dr. Thapa is working on the projects involved in interferon-based cell death and cell survival studies, and influenza A virus (IAV)-induced Receptor Interacting Protein Kinase 3 (RIPK3)-dependent cell death pathways. His future plans are to identify regulatory molecules involved in programmed cell death pathways, and develop therapeutic strategies targeting cell death mediators.

In multicellular organisms, programmed cell death plays a vital role in the clearance of virus infected cells. RIPK3-activated programmed cell death is essential for controlling respiratory influenza A virus (IAV) infection. IAV is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. However, how IAV activates RIPK3 is unclear. Dr. Thapa’s group reports that DAI recognizes IAV RNA by a mechanism requiring the second of its Z alpha domains, and nucleates a RHIM-dependent RIPK3-containing necrosome. DAI also mediates IAV-induced RIPK3-independent apoptosis. Consequently, cells lacking DAI are remarkably resistant to IAV-triggered lysis, and DAI-deficient mice are hyper-susceptible to lethal infection by this virus.  These findings identify DAI as a central mediator of IAV-driven cell death, and implicate this protein as a sensor of influenza A virus.


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