The focus of my laboratory is to understand the molecular basis by which bacteria (Gram-negative and positive) modify the lipid component of their membrane and how these alterations affect or circumvent normal host innate immune system responses. These modifications can promote resistance to host innate immune killing mechanisms by antimicrobial compounds and alter recognition by TLR4. To the end, I have extensive experience in the discovery and analysis of various structural modification of lipopolysaccharide (LPS), the major component of the Gram-negative bacterial envelope and lipoteichoic acid (LTA), the major component of the Gram-positive bacterial. In addition, we have been using a variety of infection routes (aerosol, subcutaneous, IP) to determine the role of the host innate and adaptive immune systems in the control of mutant strains with defects in enzymes required for lipid biosynthesis. We are utilizing mass spectrometry, gas chromatography, and bioinformatics to identify genes required for lipid biosynthesis and their interactions with the host innate immune system, specifically components of the TLR4 complex.

Additionally, I serve as the Co-Director of the recently established Spatial Systems Biology Laboratory (SSBL), a spatial ‘omics imaging biocontainment suite for workflows developed specifically for a variety of BSL-2, BSL-3, and select agent BSL-3 pathogen models at the University of Maryland School of Dentistry. We are currently developing a novel lipidomic approach for rapidly identifying bacterial and fungal organisms directly from urine, blood, BAL fluid without the need for culture and an associated machine learning/AI software package that can be used to automatically identify organisms directly from mass spectrum. We have also commenced a large-scale surveillance project to identify microorganisms from the Chesapeake Bay that grow at reduced temperatures using lipidomics, where these results will be combined with sequence metagenomics of bulk water samples and 16S sequencing of individual organisms with researchers at the US Naval Academy. Finally, through the characterization of lipid A biosynthetic enzymes, we have developed unique TR4 agonists that are currently being developed as vaccine adjuvants.