Project Grant R01HL177113

Award Date 1/25/25
Completion Date 11/30/28
Dollars Obligated $634K
Federal Grant Program
93.837
Assistance Type
Project Grant
Place of Performance
Missouri, USA
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The National Heart, Lung, and Blood Institute (NHLBI) awarded a $633,720 Project Grant (CFDA 93.837 - Cardiovascular Diseases Research) to The Washington University in St. Louis to support research focused on understanding protein arginylation and its role in cardiovascular development and disease. The key objectives of this 4-year project include:

  1. Establishing a chemical proteomics platform to comprehensively profile arginylation sites in cardiac cells and clinical heart tissue samples to elucidate the prevalence and biological functions of this post-translational modification.

  2. Investigating the impacts of protein arginylation on cardiovascular development, particularly its effects on epigenetic mechanisms and cardiac differentiation, using a combination of mass spectrometry, biochemistry, and next-generation sequencing techniques.

  3. Developing an "arginylation targeting chimera" (ArgTAC) technology to explore the therapeutic potential of targeted protein arginylation and degradation, such as for lowering LDL levels.

  4. Conducting CRISPR screening to identify putative de-arginylation enzymes that could reverse this post-translational modification.

This research aims to unveil the prevalence and novel biological roles of protein arginylation, and establish new technologies to advance the understanding and potential therapeutic applications of this essential post-translational modification in cardiovascular biology and disease.

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