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Methodologies and Techniques

• Echocardiography
• Cardiac surgeries and phenotyping- mammalian models
• Histology
• Microscopy- fluorescent, confocal
• Flow cytometry
• FACS sorting
• Polymerase Chain Reaction
• Molecular cloning
• Western blotting
• Cell culture- primary cardiac cells
• RNA sequencing (bulk and single cell RNA sequencing)
• Genetics/Genomics

Research Interests
Overarching concept:
Higher organisms such as zebrafish and neonatal mice are capable of complete heart regeneration following partial amputation. Although adult humans and adult mice lack this regeneration response, there is great interest in understanding how heart regeneration can occur in lower organisms so that we can activate pro-reparative processes in humans to better treat patients following myocardial infarction. My lab is interested in understanding the cell biology and molecular pathways that facilitate heart regeneration, repair, and cardiomyocyte cell cycle activity.

Interleukin 4/13 signaling:
Cytokines and growth factors play a significant role in the initiation of tissue and organ regeneration in large part by directly stimulating proliferation of resident cells, or by recruitment and activation of wound healing inflammatory cells. The type II cytokines Interleukin 4 (IL4) and Interleukin 13 (IL13) are well known to mediate type II immunity, but also can signal to non-hematopoietic cell types. Our lab is interested in studying the various cell types in the heart that respond to IL4/13 during homeostasis and post injury, as well as the cell types producing these cytokines. Overall, IL4/13 signaling in the heart improves the reparative response and cardiac outcomes post injury, therefore understanding the mechanism(s) by which these cytokines improve cardiac function could lead to new therapeutic strategies for treating heart failure.

Cytoarchitectural proteins in cardiomyocyte function:
Cardiac regenerative approaches aimed to drive proliferation of CMs have shown great promise in recent years. However, there is currently poor understanding as to how cell structural changes are regulated to promote cell cycle re-entry, and importantly the factors that facilitate re-integration of CMs into the functional myocardium. This latter point is particularly significant as driving CM cell cycle itself can lead to adverse phenotypes such as heart failure or arrhythmia. Considering the importance of the intercalated disc (ICD) and CM cytoskeletal structure in regulating cell signaling and maintaining cardiac function, we aim to understand the proteins that control CM cytoarchitecture and re-establishment of ICD during cardiac development, regeneration, and repair.

Genetic determinants underlying cardiac repair:
The physiological response to cardiac injury such as myocardial infarction is highly variable in humans. Emerging literature has identified several cardiac cell types that are thought to protect individuals from adverse outcomes following injury, and even promote some degree of myocardial regeneration. Specifically, emerging evidence demonstrates that cardiac resident macrophage populations promote reparative healing in the context of cardiac injury. Macrophage subtypes are present in the steady state heart prior to injury, are present at variable frequencies across genetically inbred rodent strains, and are easily quantifiable. We leverage genetically diverse rat models to determine frequency and sub-type of tissue resident cardiac macrophages in the steady state heart and determine how these populations relate to outcomes after myocardial injury. This project is in collaboration with Dr. Michaela Patterson’s lab.

Training and Mentoring
A priority of mine is high quality training of the next generation of scientists. Graduate students and postdoctoral in the O’Meara lab have been recipients of independent NIH F31 and F32 grants and have been awarded placement on competitive predoctoral and postdoctoral T32 training grants. We are currently recruiting graduate students and postdoctoral fellows to work on highly collaborative and innovative cardiac repair research projects.