Lok Raj Joshi

Research Interests

1. Viral Vectors for Vaccine and Gene Therapy: In our laboratory, we engineer viruses to use them as gene delivery vectors. Live viral vectors are known for their safety and immunogenicity, making them promising candidates for vaccine development. Viral vector vaccines elicit robust humoral and cellular immune responses, offering superior protection compared to traditional vaccines. Our research primarily focuses on engineering poxvirus to develop them as vaccine vectors. We have successfully demonstrated the efficacy of a parapoxvirus, orf virus, as a vaccine vector for delivering antigenic proteins. We have utilized orf virus to deliver the spike protein of alphacoronavirus and the hemagglutinin protein of influenza A virus in the swine model.  Research in our lab also focuses on the rational engineering of poxviral vectors to improve their safety and efficacy. We also use adeno-associated virus (AAV) as a gene delivery vector to express therapeutic proteins for gene therapy applications.
2. Virus Evolution: Viruses undergo continuous evolution, leading to the emergence of new strains that may evade existing vaccines, facilitate cross-species transmission, and occasionally can result in pandemic outbreaks. We use next-generation sequencing and bioinformatics tools to monitor the dynamic genomic landscape of viruses. We also conduct functional assays to understand the impact of new mutations on viral fitness and their ability to evade immune responses.
3. Virus Pathogenesis and Diagnostics: There has been a surge in the emergence and re-emergence of viral pathogens, both in animals and humans, some of which possess zoonotic potential. It is important to investigate the pathogenesis of these novel viruses using appropriate animal models.  A pathogenesis study entails a comprehensive analysis of host factors, transmission dynamics, tissue and organ tropism, clinical and pathological manifestations, and host immune response to the infectious agent. Previously, we performed a series of experiments to study the pathogenesis of Senecavirus A, a re-emerging picornavirus of swine. Our current research interest involves studying the pathogenesis of emerging avian influenza viruses and their potential to infect humans and other animal species. Additionally, we are actively involved in the development of diagnostic tools and reagents essential for epidemiological studies and the molecular characterization of novel viruses. We develop monoclonal antibodies and serological assays for disease surveillance. We also utilize metagenomic tools for rapid identification and molecular characterization of emerging viruses.