Biography
Sabine Ehrt received her Ph.D. in Microbiology from the Friedrich-Alexander University Erlangen-Nürnberg, Germany, in 1994. As a postdoctoral fellow she started her work on the human pathogen Mycobacterium tuberculosis with Dr. Lee Riley at the Department of International Medicine and Infectious Diseases at Cornell University Medical College and at the School of Public Health at UC Berkeley. In 1999, Dr. Ehrt joined the faculty of the Department of Microbiology and Immunology at WCMC. She is a recipient of an Irma T. Hirschl Career Scientist Award and an Excellence in Mentoring Award from the WMC Postdoctoral Association. Dr Ehrt was promoted to Associate Professor in 2005 and was awarded with tenure in 2008. She serves as director of the Biosafety Level 3 (BSL3) facility at WCMC and is co-director of “Microbial Pathogenesis”, a graduate course run jointly between the Immunology and Microbial Pathogenesis Graduate Program and Rockefeller University. Dr. Ehrt serves regularly as temporary member of the “Host Interactions with Bacterial Pathogens (HIBP) and “Bacterial Pathogenesis” (BACP) study sections at the NIH. She will be a permanent member of HIBP starting October 2009. She is an editorial board member of “Infection and Immunity” and serves as ad hoc reviewer for a variety of scientific journals including Science, Nature, Nature Medicine, Journal of Experimental Medicine, Molecular Microbiology, Journal of Immunology, Cellular Microbiology, Plos Pathogens, Journal of Infectious Diseases.
Dr. Ehrt’s research is centered on the pathogenesis of tuberculosis (TB). She investigates the role of the macrophage in the immune response to Mycobacterium tuberculosis and the molecular mechanisms used by the pathogen to establish persistent infections. Dr. Ehrt has extensively characterized the global gene expression profile of Mtb infected macrophages. This demonstrated that two antimicrobial enzymes, nitric oxide synthase-2 and phagocyte oxidase, help orchestrate the pathogen-induced profound transcriptional remodeling. Gene expression analysis of macrophages lacking the intracellular Toll-like receptor (TLR) adapter MyD88 revealed a previously unappreciated role of MyD88 in IFNγ-dependent macrophage activation. Recently, work by her group established that RP105, a cell surface molecule, not previously implicated in the pathogenesis of TB, functions as an accessory molecule for TLR2 in sensing mycobacterial lipoproteins.
A goal of Dr. Ehrt’s research is to validate novel drug targets that may facilitate the development of new therapies against active and chronic TB. In collaboration with her colleague Dr. Schnappinger, she developed mycobacterial gene expression systems to construct conditional knockdown mutants of Mtb, in which expression of a target gene can be silenced either by addition (Tet-OFF) or removal of tetracyclines (Tet-ON). These systems allow determining if a particular gene is required by Mtb to sustain a chronic infection and enable the analysis of essential genes for which conventional gene deletion strains cannot be generated. Dr. Ehrt applied these systems to regulate genes encoding the mycobacterial proteasome and showed that silencing of proteasome expression interfered with the Mtb’s ability to cause chronic infections in mice. This work validated the Mtb proteasome as a potential novel drug target.
Collaborative work by Dr. Ehrt and Dr. Nathan challenged a prevailing view that Mtb chiefly relies on its ability to interfere with phagosome maturation and acidification. In fact, Mtb requires active mechanisms of pH homeostasis to cause disease and maintain a chronic infection. A serine protease was shown to be essential for intrabacterial pH maintenance of Mtb residing in IFNγ-activated macrophages and for virulence in mice. Current work is ongoing to investigate the mechanism by which this enzyme protects Mtb from acid and to explore pH homeostasis as target for the development of new chemotherapeutics.
Dr. Ehrt’s research program has maintained continuous funding from the National Institutes of Health and is supported by the Bill & Melinda Gates Foundation and the Wellcome Trust.
