Current Research and Scholarly Interests
Our lab has several major focuses:
1. The role of alterations in mitochondrial structure and function in normal physiology (such as exercise) and in disease such as dilated and hypertrophic cardiomyopathy.
2. Single cell analysis of mitochondrial function reveals significant heterogeneity.
3. Differences between right and left ventricular responses to stress and in their modes of failure, including gene expression and miR regulation.
4. Using iPSC-derived cardiomyocytes to develop a better understanding of hypertrophic cardiomyopathy and congenital heart disease.
5. Use of iPSC-CMs in pharmacogenomics, specifically determining the role of gene variants in doxorubicin cardiotoxicity.
Specific projects underway in our lab include:
1. Alterations of mitochondrial structure and function, including processes of mitofusion, mitofission, autophagy and mitophagy, in normal physiology and disease.
2. Development of high-throughput single cell imaging technologies to measure single cell mitochondrial function, and to measure single mitochondrial function to determine the role of heterogeneity in cell life-death decision-making.
3. Differences between the right and left ventricles in their responses to stresses such as increased afterload and increased preload, including gene expression and gene regulation by micro-RNAs. The use of plasma miRs as biomakers for RV failure.
4. Using patient-derived iPSC-cardiomyocytes to understand the mechanisms of cardiomyopathies common in children and to solve the genotype-phenotype conundrum in hypertrophic cardiomyopathy.
5. Development of micro-engineered platforms for assessment of biomechanics of single iPSC-derived cardiomyocytes.
6. Developing tools to further mature hiPSC-CMs to more accurately recapitulate the mechanobiology of adult human CMS.
We also are interested in clinical cardiac transplantation in children, specifically:
1. Understanding alterations in immune system function in patients with single ventricle physiology after the Fontan operation.
2. Development of biomarkers for the detection and monitoring of post-transplant lymphoproliferative disorder in pediatric transplant patients.
3. Immune system biomarkers that predict adverse outcomes after pediatric VAD implantation.