The Role of LLGL1 in Cardiac Development and Regeneration

Informing therapeutic targets for Wisconsin patients suffering from progressive heart failure

Full Project Name:The Role of LLGL1 in Cardiac Development and RegenerationPrincipal Investigator:Brian A. Link, PhD, Cell Biology, Neurobiology and AnatomyCo-Investigator:Caitlin C. O'Meara, PhD, PhysiologyAward Amount:$250,000
Award Date
July2020
Project Duration:24 months

Project Description Narrative:


Cardiac disease is the leading cause of death in both men and women in Wisconsin, bringing huge emotional and economic impacts to families. Over 16,000 deaths were attributed to cardiovascular disease in Wisconsin in 2017, at an estimated cost of more than $7.5 billion.

Myocardial infarction (MI), also known as a heart attack, is the most common form of fatal heart disease in Wisconsin. Although most patients survive a heart attack, the adult human heart fails to appropriately heal or regenerate, resulting in progressive heart failure. In recent years, the scientific community has made exciting advances in the field of adult heart regeneration, including discovery of a molecular signaling pathway called the Hippo-Yap network that can profoundly stimulate adult heart muscle cells to divide and proliferate. While these findings have clear implications in promoting cardiac healing in adult hearts, how the Hippo-Yap pathway is regulated and whether it can be fine-tuned therapeutically is not comprehensively understood.

Through this award, a collaborative research team aims to understand how the Hippo-Yap pathway can be regulated at a molecular level in the heart, informing therapeutic targets for patients suffering from progressive heart failure.

Additional collaborator:
Michaela Patterson, PhD, Medical College of Wisconsin Cell Biology, Neurobiology, and Anatomy

Outcomes & Lessons Learned:


  • Found that the loss of the protein LlGl1 results in several pro-cardiac regeneration pheynotypes, including activation of the YAP transcription factor, a protein involved in the process of transcribing DNA into RNA; rapid reproduction of cardiomyocytes, cells responsible for generating contractile forces in the heart; and an increase in the number of mono-nuclear diploid cardiomycytes
  • Identified a node factor that may coordinate the process of cytoarchitectural modifications, the structural arrangement of neurons within the central nervous system, with cardiomyocyte proliferation
  • Project results have implications for promoting cardiac regeneration in non-regenerative mammals

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