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LincRNAs and Stem Cells

Our research is centered on stem cell differentiation of the cardiac lineage and heart development. One of our goals for this research is to characterize the epigenetic and transcriptome changes that occur during early embryonic heart differentiation.  Specifically, We are interested in the epigenetic modifications involving long, intergenic non-coding RNAs and their role in defining the cardiac lineage. Recently, lincRNAs have emerged as one of the most important regulatory paradigms in mammalian biology by partnering with genomic enhancer regions and thereby co-activating and/or co-repressing transcriptional activity of the targeted genomic region. It is plausible that lincRNAs can regulate histone “readers,” “writers,” or “erasers” allosterically altering their ability to modulate repressive or enhancive epigenetic marks.



Transcriptional and Epigenetic regulation of

 cardiac Stem Cells

We are interested in transcriptional and epigenetic regulation of cardiac stem cells in the context of vertebrate embryogenesis causing human congenital heart defects (CHDs), and their implications in adult cardiac muscle regeneration. In particular, We are interested in determining the roles of transcription factors and molecular signalling pathways in cardiac lineage specification, including T-box transcription factors, Wnt signaling, Notch signaling, and the role of epigenetic chromatin remodeling complexes including Polycomb Repressive Complex 2 (PRC2) and BAF complex. Our goal is to obtain an in-depth understanding of these molecular pathways in order to prevent neonatal CHDs and efficiently regenerate heart muscle in adult patients with irrevocable heart diseases.

Molecular regulation of Heart development

Heart development involves the precise orchestration of a complex gene expression program in order to convert primitive mesenchyme into a complex muscular organ with 4 chambers, valves, inflow and outflow tracts. A variety of transcription factors and coregulators control the heart development gene program. The goal of our research is to understand the physiological function of these factors and determine the molecular mechanisms though which they regulate gene expression. To this end, we use genetically engineered mice to determine the role of specific transcription factors and coregulators in the process of heart development, gene expression profiling to determine which genes are controlled by these factors, and a variety of biochemical techniques to determine how they work at the molecular level. This work will lead to an in-depth understanding of the cardiac differentiation program, yielding basic knowledge useful in the diagnosis of congenital heart defects and design of biomedical interventions for the treatment of heart diseases.

Cardiac progenitor cells (CPCs)

We are interested in the fate commitment and maturation of cardiac progenitor cells (CPCs). CPCs hold a unique position in heart regenerative medicine for a number of reasons. First, they can differentiate into multiple cardiovascular lineages, including smooth muscle, endothelial, and cardiac muscle for a concerted therapeutic effect.  Second, unlike totipotent ES cells, they do not form tumor when grafted. Third, unlike terminally differentiated cells, they are proliferative thus a relatively small amount may be sufficient for therapeutic effects. We are studying what extracellular cues induce CPCs and what signaling pathways drive the differentiation of them into the major cardiovascular lineages. In collaboration with other labs in the college, we are exploring the opportunity to use CPCs for experimental therapy in moue heart disease models.

Another related research interest is the function of endoderm in cardiac differentiation. Previously, We have found that the endoderm protein Sox17 has a pivotal role in inducing CPCs. We are delinearizing this pathway, in hope to ultimately find the secreted factor mediating the induction of CPCs.