Dr. William R. Jacobs, Jr.'s Lab
Study of mycobacterial genomics and identifying critical determinants of the pathogenicity of M. tuberculosis. Design of new cloning vectors and development of high-trough-put technologies for creating a comprehensive gene knockout library of M. tuberculosis "4049 genes - 4049 knockouts" that reveals the genetic regulatory mechanisms of pathogenicity: Ko, Annie, Mei, Morad, Masa, Kari, Rainer, Paras.
Deciphering the mechanisms that underlie bacterial dormancy and the persistence of tuberculosis infection that result from host-pathogen interactions. Identifying the factors, mechanisms and pathways that lead to the long-term dormancy and the survival in the host of M. tuberculosis, such as hypoxia and the different metabolic switches or biosynthesis and the accumulation of "storage" polymers like glycogen, polyphosphate, long-chain fatty acids: Jordan, Tony, Rainer, Catherine, Apoorva, Robert, Regy.
Study of the mechanisms of drug susceptibility and resistance, and the discovery of new drug targets and new and more effective drugs for the treatment of tuberculosis. Understanding of how drugs like isoniazid, ethambutol, pyrazinamide, rifampin, etc., kill mycobacteria; why bacteria like M. tuberculosis can survive long-term treatment; the genetic mechanisms of drug susceptibility and resistance; the drug targets of M. tuberculosis; the factors contributing to the development of a phenotypic drug resistance; and discovery of more effective drugs and treatment approaches in the fight against tuberculosis: Apoorva, Catherine, Michelle, Jordan, Torin, Mary.
Elucidating the importance of innate immune responses against tuberculosis, elaborating the mechanisms for establishing of tuberculosis infection and for its persistence in the host. - Explaining phenomena such as the following: revealing how M. tuberculosis persists in the macrophages, and how it evades the naturally existing mechanisms of intracellular killing; how bacteria can control the production of cytokines, and what mechanisms contribute to this host-pathogen interaction; and why infected macrophages can not efficiently enter into apoptosis and whether there are essential bacterial determinants contributing to these processes: Dee, Joe, Sunhee, Mi Sun, Andrew, Bing, Ka-Wing, John, Mei.
Design, construction and implementation of new vaccines capable of protecting against and preventing against tuberculosis infection. We are committed to using different genetic approaches to create vaccine strains that are more effective in protecting againest and preventing tuberculosis infection. A number of our attenuated M. tuberculosis vaccine candidate strains are undergoing rigorous testing and development in preparation for use in future Phase I human clinical trials: Michelle, Ko, Masa, Karolin, Bing, Sunhee, Apoorva, Mei, John.
