Mechanical regulation of hematopoiesis
Active Project Grant Awarded Last action
- Award ID
- F32HL168918
- Recipient
-
The University Of Texas Southwestern Medical Center UEI YZJ6DKPM4W63 Part of University Of Texas System
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $233,904
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 68% complete
- Place of performance
- Dallas, TX 75390, USA
Award details come from USAspending.gov.
Description
- Abstract
- Mechanical loading of bones is important for healthy hematopoiesis and immune function. The bone marrow is sensitive to loading-induced changes in interstitial flow and shear stress. The leptin receptor- expressing (lepr+) stromal cells in the bone marrow support both hematopoiesis and osteogenesis. Load- bearing exercise promotes the maintenance of lymphoid progenitors in the bone marrow by promoting signaling of the mechanosensitive ION channel PIEZO1 in a subset of these cells: peri-arteriolar osteolectin expressing (OLN+) cells. The hypothesis of this proposal is that another mechanically regulated ION channel, TREK1, contributes to the regulation of hematopoiesis and osteogenesis in the bone marrow. TREK1, an outwardly rectifying potassium channel that is activated by mechanical stretch and pressure, is expressed by most peri-arteriolar OLN+lepr+ cells and by a subset of other lepr+ cells. No one has investigated whether TREK1 regulates hematopoiesis or osteogenesis under physiological conditions. In aim 1, i propose to test whether TREK1 expression in peri-arteriolar OLN+lepr+ cells and peri-sinusoidal OLN-lepr+ cells regulates hematopoiesis in the bone marrow. In aim 2, i propose to test whether TREK1 expression in peri-arteriolar OLN+lepr+ cells and peri-sinusoidal OLN-lepr+ cells regulates osteogenesis in the bone marrow and whether this is modulated by mechanical loading. In aim 3, i will test whether TREK1 expression defines a biologically or spatially distinct subset of lepr+ stromal cells in the bone marrow. I will test how the deficiency of TREK1 affects hematopoietic stem/progenitor cell frequency, osteogenesis, and bone marrow reconstitution capacity. Outcomes of the proposed studies will indicate whether TREK1 modulates hematopoiesis or osteogenesis in response to mechanical loading and whether TREK1-expressing cells perform distinct functions in the bone marrow niche.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $81,580 | |
| Amendment | $78,040 | |
| Original award | $74,284 |
Quick answers
Who received award F32HL168918?
F32HL168918 was awarded to The University Of Texas Southwestern Medical Center by National Heart Lung and Blood Institute (National Institutes of Health) on January 15, 2025.
How much is award F32HL168918 worth?
$233,904 has been obligated on F32HL168918.
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