# Pharmacology

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $601,886

## Abstract

Mycobacterium tuberculosis (Mtb) is one of the world's most successful pathogens. WHO estimates that about
one third of the world's population has a positive skin test that reflects a long-term adaptive immune response
to Mtb antigens. These individuals are considered to have actual or potential latent Mtb infection (LTBl).
Among them, a minority that cannot be identified prospectively will develop reactivation tuberculosis (TB)
despite having apparently normal immunity. Active TB can be contagious both to those who were previously
unexposed and those with LTBl and is usually lethal if untreated. Adequate numbers of CD4 T cells, tumor
necrosis factor alpha (TNFα), and interferon-gamma (IFNγ) are validated determinants of control of primary
TB, but the vast majority of HIV negative patients with reactivation TB do not have defined defects in these
pathways. The ability of Mtb to remain latent within the human host, and the related failure of the human
immune system to sterilize Mtb in latently infected individuals, are poorly understood. Antimicrobial therapy for
active infection by drug-sensitive Mtb is effective, but current drugs must be given for 6 months to achieve
relapse-free cure rates of >95%. The necessity for this prolonged duration of therapy is attributable to the
ability of genetically drug-sensitive Mtb to adopt a phenotypically drug-tolerant, persistent state in which it is not
readily sterilized by current drugs. Despite substantial efforts to understand these two critical features of Mtb
infection—latency and persistence—fundamental questions remain about the genetic, immunologic, and
microbiologic contributors to both. We seek to close this knowledge gap through a Tuberculosis Research Unit
(TBRU) that unites investigators at Weill Cornell Medical College (WCMC), Rockefeller University (RU), and
Memorial Sloan Kettering Cancer Center (MSKCC), with selected external collaborators, and draws on patients
at the WCMC-affiliated GHESKIO Centres in Haiti to provide insight into latency and persistence of Mtb during
human infection.

## Key facts

- **NIH application ID:** 10057815
- **Project number:** 5U19AI111143-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Veronique Dartois
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $601,886
- **Award type:** 5
- **Project period:** 2014-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057815

## Citation

> US National Institutes of Health, RePORTER application 10057815, Pharmacology (5U19AI111143-07). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10057815. Licensed CC0.

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