K43TW011926
Project Grant
Overview
Grant Description
Prevalence and Temporal Dynamics of Clonal Mutations Associated with the Risk of Hematological Cancer in a Cohort of Clinically Healthy Nigerians - Project Summary/Abstract
The burden of non-communicable diseases, especially hematological malignancies and cardiovascular diseases (CVDs), is rising in Africa. Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related risk factor for all-cause mortality, blood cancer, and CVDs, prompting huge interests in the development of drugs targeting CHIP mutations to intercept progression to malignancies.
However, individuals of African descent are a minority in these CHIP studies hence the need to understand the spectrum and frequency of CHIP variants in African populations. My long-term research goal is to generate a pan-African database of somatic mutations associated with the risk of developing myeloid leukemia.
Recent genome-wide association analyses have identified germline loci predisposing individuals to increased risk of CHIP acquisition. These include the RS144418061 intergenic variant near TET2 found only in African-ancestry populations.
The central hypothesis is that there is a high burden of CHIP variants in normal-aging Africans compared to age-matched healthy Caucasians. To address this, I propose the following specific aims:
Aim 1 determines the frequency of CHIP mutations in a cohort of clinically healthy Nigerians. Whole blood samples from healthy Nigerian volunteers ≥40 years will be collected, and error-corrected targeted sequencing will be carried out to genotype 54 genes known to be frequently mutated in myeloid malignancies.
Aim 2 describes temporal trends and clinical outcomes of CHIP acquisition over a three-year period. Each subject will be followed up for three years, and the temporal dynamics of CHIP clonal dominance over the period will be determined. In addition, hematological changes correlating with the CHIP architecture will be described. It is suspected that varying behavioral and clinical states will impact the rate of CHIP progression in different individuals.
Aim 3 will determine the inflammatory markers associated with CHIP burden in the study population. Here, Luminex-based human cytokine/chemokine assay will be adopted to tease out inflammatory signals correlating with CHIP burden.
This K43 project will generate information on CHIP mutations in normal-aging Nigerians. This aligns with the study I am currently leading on CHIP burden in Nigerians with varying comorbidities.
My career development goal of this K43 application is to gain skills on error-corrected sequencing, variant calling, as well as data analysis and generate sufficient data for a competitive hypothesis-driven R01 submission by the fifth year of this award. This will enable me to build research capacity for blood cancer genetics in Nigeria and establish my independence as an Africa-based medical geneticist.
My training and research activities will benefit from a strong committee of mentors comprising established US and Africa-based researchers in hematology, population genetics, bioinformatics, and computational analysis. I will maximize my time at the Nigerian Institute of Medical Research carrying out hematological analysis and sequencing while taking advantage of hands-on training activities, important data science, and research leadership courses available at the National Institutes of Health.
The burden of non-communicable diseases, especially hematological malignancies and cardiovascular diseases (CVDs), is rising in Africa. Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related risk factor for all-cause mortality, blood cancer, and CVDs, prompting huge interests in the development of drugs targeting CHIP mutations to intercept progression to malignancies.
However, individuals of African descent are a minority in these CHIP studies hence the need to understand the spectrum and frequency of CHIP variants in African populations. My long-term research goal is to generate a pan-African database of somatic mutations associated with the risk of developing myeloid leukemia.
Recent genome-wide association analyses have identified germline loci predisposing individuals to increased risk of CHIP acquisition. These include the RS144418061 intergenic variant near TET2 found only in African-ancestry populations.
The central hypothesis is that there is a high burden of CHIP variants in normal-aging Africans compared to age-matched healthy Caucasians. To address this, I propose the following specific aims:
Aim 1 determines the frequency of CHIP mutations in a cohort of clinically healthy Nigerians. Whole blood samples from healthy Nigerian volunteers ≥40 years will be collected, and error-corrected targeted sequencing will be carried out to genotype 54 genes known to be frequently mutated in myeloid malignancies.
Aim 2 describes temporal trends and clinical outcomes of CHIP acquisition over a three-year period. Each subject will be followed up for three years, and the temporal dynamics of CHIP clonal dominance over the period will be determined. In addition, hematological changes correlating with the CHIP architecture will be described. It is suspected that varying behavioral and clinical states will impact the rate of CHIP progression in different individuals.
Aim 3 will determine the inflammatory markers associated with CHIP burden in the study population. Here, Luminex-based human cytokine/chemokine assay will be adopted to tease out inflammatory signals correlating with CHIP burden.
This K43 project will generate information on CHIP mutations in normal-aging Nigerians. This aligns with the study I am currently leading on CHIP burden in Nigerians with varying comorbidities.
My career development goal of this K43 application is to gain skills on error-corrected sequencing, variant calling, as well as data analysis and generate sufficient data for a competitive hypothesis-driven R01 submission by the fifth year of this award. This will enable me to build research capacity for blood cancer genetics in Nigeria and establish my independence as an Africa-based medical geneticist.
My training and research activities will benefit from a strong committee of mentors comprising established US and Africa-based researchers in hematology, population genetics, bioinformatics, and computational analysis. I will maximize my time at the Nigerian Institute of Medical Research carrying out hematological analysis and sequencing while taking advantage of hands-on training activities, important data science, and research leadership courses available at the National Institutes of Health.
Funding Goals
THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.
Grant Program (CFDA)
Awarding Agency
Funding Agency
Place of Performance
Nigeria
Geographic Scope
Foreign
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 397% from $93,105 to $462,349.
Nigerian Institute Of Medical Research was awarded
Prevalence of Clonal Mutations in Healthy Nigerians
Project Grant K43TW011926
worth $462,349
from National Heart Lung and Blood Institute in September 2021 with work to be completed primarily in Nigeria.
The grant
has a duration of 4 years 8 months and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/20/25
Period of Performance
9/22/21
Start Date
5/31/26
End Date
Funding Split
$462.3K
Federal Obligation
$0.0
Non-Federal Obligation
$462.3K
Total Obligated
Activity Timeline
Transaction History
Modifications to K43TW011926
Additional Detail
Award ID FAIN
K43TW011926
SAI Number
K43TW011926-822935886
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Non-Domestic (Non-U.S.) Entity
Awarding Office
75NF00 NIH Fogarty International Center
Funding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Awardee UEI
SAU8NDMYPL87
Awardee CAGE
SKS16
Performance District
Not Applicable
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $185,571 | 100% |
Modified: 6/20/25