This Outstanding Investigator Award R35 program addresses previously-unexplored mechanisms by which regulation of gene expression at the translational level controls the functions of megakaryocytes and platelets, in the setting of health and disease. Studies will employ basic and clinical investigations in humans and mice to comprehensively determine how translational pathways that converge on Eukaryotic Initiation Factor 4E (eIF4E) regulate megakaryocyte and platelet biology. Roles for translational control pathways in megakaryocytes have not previously been studied, their functional significance in circulating platelets is uncertain, and it is unknown how disease situations alter translational responses of megakaryocytes and platelets. Thus, successful completion of the research objectives will fill key gaps in knowledge that need to be addressed in heart, lung, and blood research. Results generated will also determine if translational control pathway inhibitors, which are currently being tested in the clinic, have off-target effects on megakaryocytes and platelets.

Public Health Relevance

This Outstanding Investigator Award R35 program will determine how cells that regulate blood clotting contribute to diseases of the heart, lung, and blood. Results generated my lead to new diagnostics and/or therapies for patients who suffer from heart attacks, sepsis, or blood disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
5R35HL145237-03
Application #
10077489
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Kindzelski, Andrei L
Project Start
2019-01-01
Project End
2025-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112