This proposal seeks to renew Research Career Scientist Award held by Dr. Subhra Mohapatra, at the James A. Haley VA Hospital in Tampa, Florida since 2018. She is also a tenured- full professor (part-time) at the VA-affiliated academic center- the University of South Florida. She is the recipient of several international/national awards and recognitions including as a Fellow of the National Academy of Inventors and a Fellow of the American Institute for Medical and Biological Engineering. Dr. Mohapatra has been a research investigator at the VA Hospital (Medicine) since 2007 and has been continuously funded with the Merit Review Award focused on cancer, traumatic brain injury (TBI), and COVID since 2016. She has been studying the basic molecular and translational mechanisms underlying the inflammation in diverse acute/chronic diseases including COVID-19, cancers, and TBI, all of which afflict VA population and contribute significantly to the overall health of the Veterans. The main premise of her research program has been to understand the mechanisms involved in the disease pathogenesis toward developing novel diagnostic/prognostic and therapeutic approaches to treat them. Current and ongoing research activities to be supported by this RCS Award focus on three areas. The first program centers on the characterization of novel virus-neutralizing nanoparticles that may serve as prophylactic and/or treatment for COVID-19 patients. In this proposal, these particles will be investigated for their potential and validated in relevant human cellular and mouse models. She is collaborating with other VA investigators in developing an additional project to develop novel siRNA-based prophylactic and therapeutic approaches targeting viral replication and cytokine storm that follows acute SARS- CoV-2 infection. The second research program focuses on the investigation of a novel combinatorial therapeutic approach in a mouse model of moderate TBI that includes an intranasal dendrimer-based nano-formulated siRNA treatment against a recently discovered target, CCL20 to reduce inflammation, and a parallel treatment to promote neuroregeneration by therapy with mesenchymal stem cells. In the third research program Dr. Mohapatra’s lab aims to investigate and test a novel targeted oncolytic viro-cell therapy for lung cancer using the mesenchymal stem cells infected by a respiratory syncytial virus infection, which is harmless for immunocompetent individuals. This project uses a 3D multicell tumoroid in vitro and biopsy-derived cultures ex vivo, which her lab has pioneered. Further, this project uses in vivo mouse models of lung cancer to evaluate the safety and efficacy of oncolytic viro-cell therapy. The project to date has attracted industry collaboration, which might lead to clinical trials. Overall, these highly innovative approaches taken together are expected to lead to high-impact clinical diagnostics and therapies for diverse diseases of Veterans and other Americ...