TLT-1 intracellular function

This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $434,658 to Oakland University to conduct research on the intracellular function of the platelet protein TREM-like transcript-1 (TLT-1). The research aims to characterize the phosphorylation sites of TLT-1 and decipher the intracellular cues that regulate its trafficking in platelets. The goal is to gain a better understanding of how TLT-1 regulates edema and its potential as a therapeutic target to control thrombosis without introducing bleeding complications. The award period runs from September 1, 2024, to August 31, 2027.

Abstract

Trem like transcript (TLT-1), is a highly abundant platelet protein that mediates the earliest states of platelet activation. Inhibition of TLT-1 function is associated with bleeding in the inflammatory arena; however vascular hemostasis does not seem to be adversely affected. Our studies have shown that TLT-1 presents itself as a potential target to control thrombosis without the introduction of bleeding. However, to pursue the therapeutic aspects of TLT-1, we must first understand the mechanisms of TLT-1 function. This project is focused on identifying the critical signaling motifs of TLT-1 function. To accomplish this goal, we have outlined two specific aims: aim 1: characterize TLT-1 phosphorylation sites, aim 2: decipher the intracellular cues that regulate TLT-1 trafficking in platelets at the completion of these aims we will have a clear understanding of the importance of the platelet to regulation of edema and how we can manipulate platelet interactions to improve disease outcomes.