The research in the Diamond laboratory focuses on the interface between viral pathogenesis and the host immune response. We study a large number of globally important pathogens including flaviviruses (West Nile, Zika, Dengue, Yellow fever, Powassan, and Japanese encephalitis viruses), alphaviruses (Chikungunya, Mayaro, Ross River, Venezuelan equine, Western equine, and Eastern equine encephalitis viruses), and coronaviruses (SARS-CoV-2) in the context of infection at specific tissue sites (brain, respiratory tract, gastrointestinal tract, joint, and maternal-fetal interface) to understand basic mechanisms of pathogenesis, protective and pathogenic immune responses, and viral immune evasion. We have studied basic mechanisms of innate immune recognition of viruses and consequent priming of adaptive B and T cell responses. We use existing and newly generated gene-targeted mice to define key host factors and cell types that regulate infection and pathogenesis. Layered on these studies are experiments that evaluate effects of metagenomic interactions with commensal bacteria, metabolites (bile acids and short chain fatty acids) and enteric helminth infections.
We study a large number of globally important pathogens including flaviviruses (West Nile, Zika, Dengue, Yellow fever, Powassan, and Japanese encephalitis viruses), alphaviruses (Chikungunya, Mayaro, Ross River, Venezuelan equine, Western equine, and Eastern equine encephalitis viruses), and coronaviruses (SARS-CoV-2).
Our laboratory also has a long-standing interest in understanding how viruses enter cells and how antibodies neutralize entry and infection. Using genome-wide CRISPR loss-of-function or activation screens, we have identified several novel receptors for alphaviruses and flaviviruses (e.g., MXRA8 and LDLRAD3), and additional molecules are being studied. With our structural biology colleagues at Washington University and Purdue University, we have used high-resolution cryo-electron microscopy analysis of the virus-receptor interface to inform the generation of decoy receptor molecules with therapeutic potential. We also have generated thousands of murine and human monoclonal antibodies to define mechanisms of neutralization of flaviviruses, alphaviruses, and coronaviruses and establish correlates of protection in vivo. This information has informed our vaccine efforts (adenoviral-vectored and mRNA) with academic and commercial partners culminating in approval and use in humans of an intranasal adenoviral vectored vaccine against SARS-CoV-2 and preclinical development of mRNA vaccines against coronaviruses and flaviviruses.