# A multi-disciplinary approach to the identification of host metabolic determinan

> **NIH NIH U19** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $627,819

## Abstract

Although only a minority of individuals infected with Mycobacterium tuberculosis progress to active disease, 
host factors associated with progression are only poorly understood. Recent data show that metabolic risk 
factors such as low body-mass index, metabolic syndrome and type 2 diabetes mellitus are strong predictors 
of an individual's risk of progressing to active disease after infection. Further, growing evidence suggests a 
link between an individual's metabolic state and control of human macrophage and dendritic cell activation 
and differentiation pathways. Here, we propose to identify key host metabolic pathways involved in TB 
progression in a genetic study of an existing TB exposed cohort and then test these associations by 
performing observational studies in humans and intervention studies in guinea pig models. First, we will 
leverage our existing cohort of microbiologically confirmed TB index cases and their exposed, infected 
household contacts who have remained disease free for two years after exposure. Using a nested case 
control study design, we will assess the impact of genetic variants known to affect key metabolic traits as 
well as rare coding variants on TB progression using exome chips that are optimized for the Peruvian 
population in which we work. Second, we will use the results of this study to guide further validation of these 
determinants through transcriptional profiling of human myeloid cells from cases and exposed non-diseased 
controls. In a sub-study, we will also these exome chip and transcriptional profiling data to identify the genes 
involved in dendritic cell maturation as assessed by genes related to CD1, interleukin-1 and NFkappaB. To 
further explore the impact of these metabolic and immune pathways, we will conduct TB infection 
experiments in guinea pigs in which metabolic status is modified through dietary and pharmacological 
interventions with the aim of identifying possible therapeutic interventions that could moved to human trials in 
future work.

## Key facts

- **NIH application ID:** 9857531
- **Project number:** 5U19AI111224-06
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MEGAN B MURRAY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,819
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857531

## Citation

> US National Institutes of Health, RePORTER application 9857531, A multi-disciplinary approach to the identification of host metabolic determinan (5U19AI111224-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857531. Licensed CC0.

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