Our laboratory studies persister cells, uncultured bacteria, Lyme Disease and has an active natural products drug discovery program.
Persisters are dormant variants of regular cells which are tolerant to antibiotics and responsible for recalcitrance of a variety of chronic infections, including tuberculosis and those caused by microbial biofilms. We identified a number of mechanisms for persister formation, and the first compound that kills them, acyldepsipeptide.
Uncultured bacteria make up the majority of species on the planet, but do not grow in the lab. We developed a general method to grow these organisms by cultivation in their natural environment. In marine sediment, siderophores from neighbors serve as growth factors for uncultured bacteria. We have recently identified growth factors for uncultured bacteria from the human microbiome. We also use uncultured bacteria as a source for discovering new antibiotics.
Our goal is to understand the nature of PTLDS (Chronic Lyme Disease) and identify treatments for this debilitating condition. We are exploring this through several parallel approaches, gathering data on the microbiome and metabolome of PTLDS patients as well as epidemiological analysis of large datasets. We are conducting experiments to understand the nature of persistence in Borrelia burgdorferi, and have a high-throughput drug discovery program to identify novel antimicrobials with potent and specific activity against the pathogen.
We have an active natural product drug discovery program with a focus on compounds active against Gram Negative pathogens, Mycobacterium tuberculosis and Borrelia burgdorferi.