This federal Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) provides $101,491 to Cold Spring Harbor Laboratory (CSH) to conduct research aimed at understanding and targeting cell senescence in clonal hematopoiesis (CH). The award will fund two main research efforts:
Identifying inflammatory mediators of CH-mutant hematopoietic stem and progenitor cells and evaluating their potential as therapeutic targets to restore oligoclonal hematopoiesis (Aim 1). This includes high-throughput CRISPR/Cas9 screening to find inflammation-associated genes that confer a selective advantage to CH-mutant cells.
Uncovering the transcriptional and epigenetic mechanisms by which age-related inflammation promotes CH and potential malignant transformation to leukemia (Aim 2). This research will leverage human samples to validate the findings from the mouse models.
The project aims to develop new therapies targeting inflammation to halt or revert CH and mitigate its clinical effects, such as increased risk of hematological malignancies, cardiovascular disease, and mortality from solid tumors. The award has a period of performance from Jan 1, 2025 to Dec 31, 2028.