Weill Cornell Medical College (Tri‐I TBRU)
Primary Investigator: Sabine Ehrt: Michael Glickman (Sloan Kettering Institute for Cancer Research)
Mycobacterium tuberculosis (Mtb) continues to be a severe global health problem. A central clinical and microbiologic feature of the disease is the ability of Mtb to resist complete elimination, both by the host immune system and by chemotherapeutic agents with potent growth inhibitory activity. This persistence in the face of immunologic and antibiotic pressure underlies several important facets of tuberculosis (TB) disease, including 1) the existence of latent tuberculosis infection (LTBI) and, in the setting of immunologic failure of LTBI control, its role in the genesis of active TB; and 2) the prolonged course of TB antibiotic therapy, which requires six months of multidrug therapy to achieve reliable clinical cure. Rather than producing complete bacterial eradication in all treated subjects, cure following TB chemotherapy is now understood to be an antibiotic induced paucibacillary state in which prevention of relapse depends in part on poorly understood host factors. The host and bacterial determinants that mediate these two interrelated types of persistence are only partially understood, a knowledge gap the Tri-I-TBRU aims to fill. The TBRU research focuses on on different facets of the problem of paucibacillary TB, both post treatment and LTBI, using samples and clinical data from TB cohorts at a clinical site in Haiti to examine the immunologic, microbiomic, transcriptomic, pharmacokinetic, and genetic factors that influence or predict the transition points between paucibacillary states of TB disease and active transmissible infection. These studies will be compared and contrasted with a mouse model of paucibacillary infection that will allow researchers to test mechanistic hypotheses about the host and bacterial determinants of paucibacillary disease.
For more information about the TBRU’s projects, please see the following summaries in RePORTER:
Determinants of TB control, relapse and infection
- Project 1: Microbiome in TB treatment response and disease resolution; Project leader: Michael Glickman
- Project 2: Human Genetics of Tuberculosis; Project leader: Jean Laurent Casanova
- Project 3: Determinants of Paucibacillary Mtb Infection in Mice; Project leader: Sabine Ehrt
- Administrative Core; Core leader: Sabine Ehrt
- Clinical Core; Core leader: Daniel W Fitzgerald
- Pharmacology and Immunopathology Core; Core leader: Veronique Dartois (Hackensack Meridian Health)