William R. Jacobs Jr. , Ph.D.
Professor of Genetics
Professor of Microbiology and Immunology
Howard Hughes Medical Institute Investigator
National Academy of Sciences Member
Location: Room 577, Price Center/Block Research Pavilion
Journal of Infectious Diseases
GM-CSF differentiated primary human macrophages produce extracellular traps (picogreen staining in green) in the presence of IFN-gamma at 2 days post-infection of M. tuberculosis (visualized by auramine-rhoamine staining in red) (See Wong and Jacobs, pp 109–19Tuberculosis, caused by Mycobacterium tuberculosis, causes one in four avoidable deaths in the Third World and kills more adults than malaria, AIDS, and all tropical diseases combined. In recent years, there have been dramatic increases in the numbers of new cases worldwide - one of the consequences of the AIDS epidemic. In addition to these increasing incidences, there has been an emergence of M. tuberculosis strains that are resistant to all seven anti-tuberculosis agents. These alarming trends have caused the World Health Organization to declare tuberculosis a global health emergency, a distinction never accorded another disease. My laboratory has focused its efforts on developing systems to genetically manipulate mycobacteria, particularly M. tuberculosis.
These tools have allowed us to:
- develop the luciferase reporter phage assay for rapid assessment of drug susceptibilities,
- analyze the genes involved in resistance to tuberculosis drugs such as isoniazid, ethionamide, and etyhambutol, and
- to identify specific phenotypic properties associated with a tuberculosis pathogenesis.
Current research efforts are aimed at identifying genes involved in the virulence of M. tuberculosis, identifying novel drug targets, generating rapid and robust phage diagnostics for drug resistant strains of M. tuberculosis, and engineering attenuated mutants of M. tuberculosis and other mycobacteria that can be used as live-cell tuberculosis vaccines.