K43TW012587
Project Grant
Overview
Grant Description
Insulin-like growth factor-1 (IGF-1) signalling in immunometabolism of TB and TB-diabetes comorbidity - summary
Type 2 diabetes mellitus (T2DM), is a life-threatening metabolic disease that increases TB incidence and mortality in South Africa and worldwide. Dysregulation of glucose homeostasis leads to the development of hyperglycaemia. Amongst newly diagnosed T2DM patients, hyperglycaemia is associated with TB/T2DM co-morbidity.
Sustained hyperglycaemia results in enhanced sensitivity to insulin-like growth factor-1 (IGF-1) in vascular endothelial and smooth muscle cells. IGF-1 influence the innate immune system and predominantly produced by monocytes/macrophages after hepatocytes. We have identified a transcriptomic signature of increased IGF-1 in IL-4-stimulated macrophages in TB infection.
Others have shown that IGF-1 facilitates alternative activation and ablation of macrophage-IGF-1R hampers the inflammasome activation to reduce chronic inflammation. Clinical studies revealed that high IGF-1 levels increased the risk of T2DM and increased serum IGF-1 levels in patients with TB and TB/T2DM.
These studies represent significant advances in our understanding of IGF-1 and suggest altered immunometabolism in host immunity influencing the outcome of TB, T2DM and TB/T2DM. However, there is still much work that needs to be done as immunometabolic and immunogenetic regulations in IGF-1 signalling remain unknown in TB and TB/T2DM and a burden in Africa.
A better further understanding of the IGF-1 signalling-mediated dysregulation of immunometabolism and immunogenetics could inform new biomarkers for diagnostics and improve treatment options for patients with TB, T2DM and TB/T2DM. I hypothesize that IGF-1 immunometabolism increases the risk of TB, T2DM and TB/T2DM co-morbidity.
To test this, I propose a comprehensive career development plan comprising structured activities and mentorship opportunities to determine the function of IGF-1 by acquiring advanced skills in (1) metabolic studies in patient samples; (2) bioinformatics to identify genetic variants in clinical datasets and functional interrogations in primary human macrophages; (3) assess an IGF-1R inhibitor as adjunctive therapy in the C3HEB/FEJ mice.
The research proposed is highly relevant to regional/global health priorities, and the career development of the PI. The project PI, Dr Suraj Parihar, is an immunologist at the University of Cape Town, South Africa, that wants to conduct research that will improve life quality of patients having grown up in India and seen first-hand the impact of TB as a significant public health problem.
This K43 award will position him to build an independent program of research and establish a unique scientific niche in macrophage immunometabolism and immunogenetics that drives innovative diagnostic and therapeutic approaches for patients in developing world.
Type 2 diabetes mellitus (T2DM), is a life-threatening metabolic disease that increases TB incidence and mortality in South Africa and worldwide. Dysregulation of glucose homeostasis leads to the development of hyperglycaemia. Amongst newly diagnosed T2DM patients, hyperglycaemia is associated with TB/T2DM co-morbidity.
Sustained hyperglycaemia results in enhanced sensitivity to insulin-like growth factor-1 (IGF-1) in vascular endothelial and smooth muscle cells. IGF-1 influence the innate immune system and predominantly produced by monocytes/macrophages after hepatocytes. We have identified a transcriptomic signature of increased IGF-1 in IL-4-stimulated macrophages in TB infection.
Others have shown that IGF-1 facilitates alternative activation and ablation of macrophage-IGF-1R hampers the inflammasome activation to reduce chronic inflammation. Clinical studies revealed that high IGF-1 levels increased the risk of T2DM and increased serum IGF-1 levels in patients with TB and TB/T2DM.
These studies represent significant advances in our understanding of IGF-1 and suggest altered immunometabolism in host immunity influencing the outcome of TB, T2DM and TB/T2DM. However, there is still much work that needs to be done as immunometabolic and immunogenetic regulations in IGF-1 signalling remain unknown in TB and TB/T2DM and a burden in Africa.
A better further understanding of the IGF-1 signalling-mediated dysregulation of immunometabolism and immunogenetics could inform new biomarkers for diagnostics and improve treatment options for patients with TB, T2DM and TB/T2DM. I hypothesize that IGF-1 immunometabolism increases the risk of TB, T2DM and TB/T2DM co-morbidity.
To test this, I propose a comprehensive career development plan comprising structured activities and mentorship opportunities to determine the function of IGF-1 by acquiring advanced skills in (1) metabolic studies in patient samples; (2) bioinformatics to identify genetic variants in clinical datasets and functional interrogations in primary human macrophages; (3) assess an IGF-1R inhibitor as adjunctive therapy in the C3HEB/FEJ mice.
The research proposed is highly relevant to regional/global health priorities, and the career development of the PI. The project PI, Dr Suraj Parihar, is an immunologist at the University of Cape Town, South Africa, that wants to conduct research that will improve life quality of patients having grown up in India and seen first-hand the impact of TB as a significant public health problem.
This K43 award will position him to build an independent program of research and establish a unique scientific niche in macrophage immunometabolism and immunogenetics that drives innovative diagnostic and therapeutic approaches for patients in developing world.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
South Africa
Geographic Scope
Foreign
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 100% from $112,586 to $225,090.
University Of Cape Town was awarded
IGF-1 Signalling in Immunometabolism of TB and TB-Diabetes Comorbidity
Project Grant K43TW012587
worth $225,090
from Fogarty International Center in July 2023 with work to be completed primarily in South Africa.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.989 International Research and Research Training.
The Project Grant was awarded through grant opportunity Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 4/5/24
Period of Performance
7/15/23
Start Date
4/30/28
End Date
Funding Split
$225.1K
Federal Obligation
$0.0
Non-Federal Obligation
$225.1K
Total Obligated
Activity Timeline
Transaction History
Modifications to K43TW012587
Additional Detail
Award ID FAIN
K43TW012587
SAI Number
K43TW012587-1708012423
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Non-Domestic (Non-U.S.) Entity
Awarding Office
75NF00 NIH FOGARTY INTERNATIONAL CENTER
Funding Office
75NF00 NIH FOGARTY INTERNATIONAL CENTER
Awardee UEI
NN5NML6VUCF9
Awardee CAGE
SBH72
Performance District
Not Applicable
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| John E. Fogarty International Center, National Institutes of Health, Health and Human Services (075-0819) | Health research and training | Grants, subsidies, and contributions (41.0) | $112,586 | 100% |
Modified: 4/5/24