Sirtuin -dependent regulation of tuberculosis and HIV interactions in macrophages
Active Project Grant Awarded Last action
- Award ID
- R01AI184551
- Recipient
-
The Methodist Hospital Research Institute UEI XJUCJAYJWYV1
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,770,623
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 46% complete
- Place of performance
- Houston, TX 77030, USA
Award details come from USAspending.gov.
Description
- Abstract
- Tuberculosis continues to kill about 1 million people including children each year with 8 million new cases. Regrettably, coinfection with HIV-1 has aggravated the problem because HIV-1 depletes CD4 T cells, which are the main defense mechanism against tuberculosis. For the reason, BCG, which is a live attenuated vaccine against tuberculosis, cannot be given to people living with HIV. We recently discovered that sirtuin type of protein and histone deacetylates play a major role in regulating the growth of both M. Tuberculosis and HIV-1 in human macrophages and drug targeting sirtuins could control both pathogens in cell culture models and in humanized mice. Therefore, we propose to investigate sirtuin-dependent intervention to understand how TB and HIV-1 infections induce these enzymes and how we can develop novel immunochemotherapy for confections. Specifically: aim-1: we will analyze the impact of early MTB and HIV infection on sirtuin gene and protein induction in macrophages and identify their epigenetic targets. We will examine the hypothesis that MTB-induced sirtuin-2 can augment HIV-1 replication, whereas HIV-1 induced sirtuin-2, in turn enhances MTB growth in MФS thereby aggravating coinfections. We will then develop an immunochemotherapy (ICT) using a combination of sirtuin drugs, TB and HIV targeting drugs to kill and eradicate both HIV-1 and M. Tuberculosis in macrophages. Aim-2: we will investigate the effect of sirtuin drugs on early and late stages of TB-HIV-1 coinfection using humanized mice and determine whether ICT can eradicate confections. Aim-3: tuberculosis granulomas can restrict growth of M. Tuberculosis pathogen, although prior infection with HIV-1 can deplete CD4 T cells and affect granuloma formation. We will use a TB-HIV coinfection model of humanized mice to determine if sirtuin-drug therapy can activate macrophages of granulomas and increase host-defense against tuberculosis. Our overall goal is to develop innovative immune defense-based intervention methods to eradicate TB-HIV coinfections.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $1,236,275 | |
| Amendment | $1,236,573 | |
| Original award | $1,297,775 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of Texas Medical Branch At Galveston | $160,000 | |
| Baylor College Of Medicine | $160,000 | |
| The University Of Texas At Tyler | $372,464 | |
| University Of Texas Medical Branch At Galveston | $240,000 | |
| Baylor College Of Medicine | $144,000 | |
| University Of Texas Medical Branch At Galveston | $143,110 | |
| University Of Texas Medical Branch At Galveston | $224,000 |
Quick answers
Who received award R01AI184551?
R01AI184551 was awarded to The Methodist Hospital Research Institute by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 1, 2024.
How much is award R01AI184551 worth?
$3,770,623 has been obligated on R01AI184551.
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