Cavity and granuloma oriented inflammation and tissue pharmacokinetics in pulmonary tuberculosis (cook TB)
Active Project Grant Awarded Last action
- Award ID
- R01AI173946
- Recipient
-
Emory University UEI S352L5PJLMP8
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $11,611,057
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 75% complete
- Place of performance
- Atlanta, GA 30322, USA
Award details come from USAspending.gov.
Description
- Abstract
- Tuberculosis (TB) is the 2ND leading cause of infectious disease mortality worldwide with ~1.5 million deaths in 2020. A hallmark of pulmonary TB is the propensity to form cavitary lesions in ~30-85% of patients. Cavities provide an ideal environment for mycobacterium tuberculosis (MTB) replication, are associated with decreased penetration of antibiotics, and can lead to irreversible lung damage. Importantly, they are associated with poor clinical outcomes including acquired drug resistance and treatment failure. Cavities develop from progression of necrotic lung granulomas; however, mechanisms underlying their formation are not clear. Improved understanding of the inflammatory responses that drive tissue necrosis and the ability of antibiotics to achieve therapeutic concentrations within necrotic granulomas are needed to 1) identify targets for host directed therapies (HDT) that can limit tissue damage and 2) to optimize antibiotic regimens. Utilizing innovative methods in imaging and spatial multiomics, we will map the distribution of transcriptional pathways and biomediators associated with human necrotic granulomas and cavities and of newly implemented anti-TB drugs in such lesions with an overall goal of providing critical new data to improve TB treatment the long term objective of this research is to provide data to guide development of a tandem therapeutic approach of optimizing anti-TB drug regimens based on their ability to reach bactericidal concentrations in all lesion areas combined with host-targeted therapies to limit pathologic inflammation. The specific aims of this proposal are to (1) identify the host metabolic and lipid phenotypes associated with each tissue region of human necrotic lung granulomas; (2) utilize spatial transcriptomics and targeted imaging to identify pathological programs associated with tissue necrosis in necrotic granulomas; and (3) utilize target site pharmacokinetics (PK) and PK modeling to enhance understanding of newly implemented anti-TB drugs. The aims of this project will be achieved by enrolling a unique cohort of patients with pulmonary TB undergoing adjunctive surgery and subsequent study of their resected lung lesions. Scientific methods employed to carry out our aims include the use of enhanced maldi-2 mass spectrometry imaging (MSI), laser capture microdissection (LCM) to isolate targeted granulomas regions for high-resolution metabolomics, lipidomics and drug concentration assays, and novel spatial transcriptomics and advanced data analytic methods to integrate spatially resolved multi-omics data sets and model target site PK data. This proposal will directly address key priories in the TB research agenda including attaining a better understanding of the determinants of m. Tuberculosis control in granulomas and how anti-TB drugs localize and penetrate into granulomas and cavities. Specific goals of the proposed work are to identify host inflammatory pathways that can be exploited for host-directed therapy and to define tissue penetrating properties of key drugs used for drug-resistant TB to optimize drug regimen design for clinical trial testing and treatment.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $51,676 | |
| Amendment | $51,676 | |
| Amendment | $51,676 | |
| Amendment | $715,817 | |
| Amendment | $715,817 | |
| Amendment | $715,817 | |
| Amendment | $762,816 | |
| Amendment | $762,816 | |
| Amendment | $762,816 | |
| Amendment | $762,816 | |
| Amendment | $76,267 | |
| Amendment | $76,267 | |
| Amendment | $686,400 | |
| Amendment | $686,400 | |
| Amendment | $686,400 | |
| Amendment | $11,880 | |
| Amendment | $11,880 | |
| Amendment | $11,880 | |
| Amendment | $801,988 | |
| Amendment | $801,988 | |
| Amendment | $801,988 | |
| Amendment | $801,988 | |
| Original award | $801,988 |
Show all 26
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| National Center For Lung Health JSC | $51,676 | |
| University Of Florida | $28,582 | |
| University Of Texas Medical Branch At Galveston | $260,237 | |
| The Regents Of The University Of California. San Francisco | $105,206 | |
| The Regents Of The University Of California. San Francisco | $31,094 | |
| National Center For Lung Health JSC | $57,076 | |
| University Of Texas Medical Branch At Galveston | $268,717 | |
| University Of Florida | $34,072 | |
| The Regents Of The University Of California. San Francisco | $3,106 | |
| University Of Texas Medical Branch At Galveston | $261,917 | |
| University Of Florida | $3,407 | |
| The Regents Of The University Of California. San Francisco | $27,985 | |
| National Center For Lung Health JSC | $57,076 | |
| University Of Florida | $30,665 |
Show all 14
Quick answers
Who received award R01AI173946?
R01AI173946 was awarded to Emory University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 9, 2023.
How much is award R01AI173946 worth?
$11,611,057 has been obligated on R01AI173946.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award