The purpose of this project is to test monoclonal antibodies in a neutralization assay with SARS-CoV-2 virus to generate IC50 values.

M. tuberculosis, which causes the worldwide global health problem tuberculosis (TB), is transmitted human to human via the airborne route into lung alveoli and ultimately exploits and grows in host macrophages. We seek to understand the cell signaling pathways initiated by infection of human macrophages with M. tuberculosis that lead to disease. Increased understanding of how macrophages are susceptible to M. tuberculosis is expected to aid in the development of host-directed therapies for TB.

The overall goal is to evaluate the potential treatment efficacy of IV-dosed galidesivir.

Exploiting the Viral RNA Methylation Machinery for SARS-CoV-2 Therapy

Unique proteins and peptides can transform salt solutions into crystals visible to the naked eye. The goal if this project is to couple these motifs to small antibodies that recognize repetitive components of pathogens so that the presence of a microbe will be signaled by the appearance of a crystal. This process could lead to the development of a new generation of inexpensive and easy to use point-of-care tests for diseases that will advance human healthcare.

We aim to fully characterize mutational signatures of SARS-CoV-19 focusing on the furin cleavage site, determine the role of the GC-rich sequence and CpG sites within the furin cleavage site and develop neutralizing Abs to target the furin cleavage site.

The major goal of this project is to elucidate the role of virus-induced events in CD40 signaling in macrophages and the importance of these signals for controlling filovirus infection. Work will use both existing and new virus stocks to challenge the selected tissues and include infection assays, cytokine/chemokine profiling, virus inactivation, analysis of infection efficiencies, and mice virus challenge.

To determine the efficiency of a novel agar-layer based test for the diagnosis of drug resistant tuberculosis in Mozambique

We will generate stocks of influenza pandemic A/California/04/09 H1N1 (pH1N1) and A/Wyoming/3/03 H3N2 influenza A viruses as well as influenza B/Brisbane/60/08 mCherry-expressing viruses that will be used to optimize the performance of PRESCIENT (Aim 1), to test the working hypothesis that PRESCIENT can identify in a mixed population of individual human hybridoma cells neutralizing antibodies against pH1N1 virus (Aim 2) and to identify influenza A H1N1, H3N2; and B virus neutralizing antibodies from EBV-immortalized patient-derived B cells (Aim 3).

The extensive genetic variability in seasonal and potentially pandemic influenza strains necessitates new vaccine strategies that can focus the immune response on generating protective antibodies against conserved targets such as regions within the influenza neuraminidase protein. We have demonstrated that seasonal immunization stimulates neuraminidase specific antibodies in humans that are broad and potent in their protection from influenza when tested in animals.