Functional metabolomics and host-Mtb interactions studies
My research focus is on the role of cholesterol for the pathogenesis of Mycobacterium tuberculosis (Mtb), the cause of approximately 2 million deaths per year worldwide. The long-term goal of this project is to determine whether cholesterol catabolism is a new therapeutic target to treat and control TB. My laboratory is interested in deciphering the cholesterol degradation pathway and identifying the oxidoreductases essential for the initial infection, as well as persistent infection. Isotopically-labeled cholesterol and high resolution LC/MS will be employed as tools to profile cholesterol-derived metabolome of knockout Mtb stains for putative cholesterol catabolic genes. The biochemical characterization of targeted enzymes will help to better understand their role during infection and evaluate their potential as therapeutic targets. The second area of research in our laboratory is to elucidate the roles of the truncated hemoglobins, HbN and HbO, for infectivity and persistence of Mycobacterium tuberculosis. HbN, which is expressed in stationary phase, is a very efficient NO-dioxygenase that was shown to protect cellular respiration against inhibition by nitric oxide in the attenuated M. bovis BCG vaccine strain. On the other hand, HbO, which is constitutively expressed, has a very high for gaseous ligands (O2, CO and NO) and appeared to be toxic when over-expressed. Collectively, these observations suggest that these two hemoglobins play different and important roles in the biology of Mycobacterium tuberculosis.