Multi-omic dissection of clonal hematopoiesis-associated diseases
Active Project Grant Awarded Last action
- Award ID
- R00HG012956
- Recipient
-
The General Hospital Corporation UEI FLJ7DQKLL226
- Awarding agency
-
National Human Genome Research Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $747,000
Award facts
- Assistance listing
- 93.172 Human Genome Research
- Completion date 75% complete
- Place of performance
- Boston, MA 02114, USA
Award details come from USAspending.gov.
Description
- Abstract
- Self-renewing cell populations accumulate somatic mutations with aging and/or in response to environmental insult and chronic inflammation. Most of these mutations in normal tissues have no functional consequence. In rare cases, these somatic mutations can confer a selective advantage leading to clonal expansion in hematopoietic stem cells, a phenomenon termed 'clonal hematopoiesis of indeterminate potential' (chip). Chip has been associated with a selective range of non-hematopoietic conditions, including coronary artery disease, stroke, heart failure, venous thromboembolism, chronic obstructive pulmonary disease, chronic liver diseases, and osteoporosis. However, the molecular mechanisms by which chip specifically promotes these diseases remain largely unknown. The overarching goal of this proposal is to molecularly connect chip with the development of associated diseases through developing and applying statistical and machine learning methods to multi-omics data in the nhlbi trans-omics for precision medicine (topmed), UK biobank, and mass general brigham biobank (mgbb). Specifically, i propose the following aims. In aim 1, i will develop a statistical method that combines multiple proteins implicated in the same pathway to improve discovery and facilitate translational insights for proteomics-based association analyses. The combined protein quantitative traits generated by this method will be used in the following aims. In aim 2, i will examine how the presence of chip and each chip driver gene specifically promote certain diseases through (1) identifying the proteomic signatures of chip and quantifying the mediation effects to associated diseases and (2) evaluating the potential modifications of chip-associated diseases by the expression levels of genes implicated in diverse molecular factors. In aim 3, i will evaluate how the progression of chip promotes associated diseases. I will examine associations between longitudinal change in the number and size of chip clones and incident disease risks, as well as generate bulk and single-cell RNA sequencing data among chip carriers with or without osteoporosis, a disease strongly associated with chip but understudied, and test for differential gene expressions between the two groups. This project's successful execution will identify the mechanisms underlying chip-associated disease risks to prioritize therapeutic targets and advance precision medicine goals.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $249,000 | |
| Amendment | $249,000 | |
| Original award | $249,000 |
Quick answers
Who received award R00HG012956?
R00HG012956 was awarded to The General Hospital Corporation by National Human Genome Research Institute (National Institutes of Health) on September 17, 2024.
How much is award R00HG012956 worth?
$747,000 has been obligated on R00HG012956.
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