Fikadu G. Tafesse, Ph.D.

According to the World Health Organization, one-third of the world’s population, almost two billion people, are infected with Mycobacterium tuberculosis (Mtb), the bacteria that causes tuberculosis (TB). This continues to negatively impact human health and the global economy and serving as one of the top drivers of antimicrobial resistance. The profound success of TB bacteria in causing disease is due to its ability to effectively utilize the body’s lipid metabolism –the process by which fatty acids are digested, broken down for energy, or stored in the human body for later energy use. While Mtb is known for modulating the lipid metabolism pathways during infection, it is not known how infective bacteria alter metabolism for lipids such as diacylglycerol (DAG) in order to invade, persist and propgate inside immune cells. We will study how this process occurs, which will help in developing new therapies for tuberculosis infection.

Update:

We are generating cell lines that lack genes involved in diacylglycerol (DAG) production. We have simultaneously begun characterizing various small molecule inhibitors that target the pathways of DAG production. Our data suggest that several of these inhibitors significantly reduce Mtb entry into host cells. In parallel, we have worked to establish several biochemical tools which will allow us to characterize the localization, dynamics, and interactions of DAG within infected cells. This research may reveal novel therapeutic targets to treat TB.