The primary objective of my research program is to develop novel strategies to help eradicate the world's most successful bacterial pathogen, Mycobacterium tuberculosis. To meet this objective, my laboratory applies a combination of approaches in genetics, biochemistry, bacterial physiology and infection biology. My commitment to tuberculosis (TB) research stems from my long-term interest in understanding critical links between bacterial physiology and mechanisms of microbial persistence. I began pursuit of these interests during my graduate studies at Tufts University where my thesis work focused on various aspects of metabolism in clinically relevant gut commensal bacteria. During my postdoctoral studies at the Albert Einstein College of Medicine, I extended my investigation of microbial metabolism to M. tuberculosis where I revealed new aspects of mycobacterial central metabolism and contributed to progress in identification and characterization of multiple novel anti-mycobacterial lead compounds. As a faculty member in the Department of Microbiology & Immunology at the University of Minnesota, I have established my research program through continuing my investigation of M. tuberculosis metabolism, persistence, drug action, and host-pathogen interaction. Our current efforts are focused on elucidating the role of innate immunity as a barrier to TB infection, understanding the unique in vivo sterilizing activity of the first-line drug pyrazinamide, circumventing major limitations in efficacy and tolerability of para-aminosalicylic acid, developing acylaminooxadiazole-based trans-translation inhibitors, advancing stable biomimetic peptides that selectively target the mycobacterial cell envelope, and characterizing numerous lead compounds with unique mechanisms of action.
