Weill Cornell Medical College has received a USD 3.6 million NIH Program Project grant to investigate the microbial determinants of tuberculosis treatment duration, with co-principal investigators Kyu Y. Rhee and Dirk Schnappinger leading a multi-project consortium aimed at shortening TB chemotherapy.
The five-year award, issued May 27, 2026, by the National Institute of Allergy and Infectious Diseases (NIAID) under mechanism P01, funds four integrated research projects and three shared cores at the institution's New York campus. The grant targets one of TB drug development's most persistent bottlenecks: the months-long treatment courses that drive poor adherence, toxicity, and ultimately treatment failure.
The scientific premise centers on phenotypically drug-tolerant bacterial subpopulations — bacteria that remain susceptible to antibiotics by conventional testing but survive chemotherapy through non-genetic mechanisms. These populations are increasingly recognized as a key biological driver of prolonged treatment duration and relapse risk.
The consortium's approach draws on the empirical track record of rifampin and pyrazinamide, two frontline agents whose addition to TB regimens enabled a roughly threefold reduction in treatment duration decades ago. Projects 1 and 2 aim to mechanistically decode how those drugs achieve treatment shortening and to translate those findings into in vitro biomarkers and novel targets.
CRISPRi and single-cell tools at the core
Projects 3 and 4 deploy more recent technologies. Project 3 applies CRISPRi (clustered regularly interspaced short palindromic repeats interference)-based genetic interaction mapping to systematically identify Mycobacterium tuberculosis drug-target combinations with enhanced bactericidal activity. Project 4 uses genetic screens to prioritize Mtb gene products whose inactivation holds the greatest potential to shorten chemotherapy duration.