The long-term research goal of my laboratory is to understand the host mediated mechanisms of innate immunity against intracellular bacterial pathogens. Over the past decade, my research has focused on elucidating the many complexities of innate immunity against Francisella tularensis, a category A biothreat agent. Our findings have yielded important insights into the role of pattern recognition receptors in protective immunity against Francisella infection. The focus of a recently renewed three-year research grant funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health is to explore how Francisella evades the host innate immune responses and blocks the development of adaptive immune responses required for protection from subsequent infections. Defining the molecular mechanism(s) of suppression of innate immunity and how this impacts adaptive immunity will be an essential first step towards development of immunotherapeutic, as well as effective vaccine strategies to combat this fatal disease.
Another area of research in the lab is to investigate the molecular mechanisms leading to the development of antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) strains. S. aureus is a major human pathogen that has demonstrated rapid emergence of resistance against novel antibiotics shortly after their introduction. Daptomycin is one of the few available intravenous antibiotics used to treat serious bloodstream infections including endocarditis secondary to MRSA. However, emergence of daptomycin resistance during therapy of MRSA-endocarditis has been documented with this high organism load infection. A three-year research grant awarded jointly by Wadsworth Center and Albany College of Pharmacy and Health Sciences is exploring the emergence of daptomycin-resistant S. aureus using a bioreactor infection model, innovative mathematical pharmacokinetic/ pharmacodynamic (PK/PD) systems analyses and advanced bioinformatics tools. Unraveling unique molecular mechanisms responsible for the emergence of daptomycin resistance is essential for the development of new antimicrobial drugs.
