Jimena Giudice, Ph.D.

Research

Alternative splicing (AS) explains how a relatively limited number of genes gives rise to a vast proteomic complexity in higher eukaryotes. It was demonstrated that AS plays a key role during differentiation and development. During postnatal heart development many physiological changes are associated with dynamic regulation of gene expression. The fetal heart adapts to birth and converts to adult function through transcriptional and posttranscriptional mechanisms, including coordinated AS regulatory networks. The human heart is composed of cardiomyocytes (CM) (<20%), cardiac="" fibroblasts="" (cf)="" (~66%)="" and="" surface="" epithelium="" and="" vascular="" cells.="" communication="" between="" cf="" and="" cm="" should="" be="" present="" early="" in="" heart="" development,="" but="" few="" investigations="" have="" addressed="" this="" issue="" in="" vivo.="" we="" are="" studying="" splicing="" regulation="" during="" heart="" development="" specifically="" in="" cm="" and="" cf.="" our="" focus="" is="" on="" events="" directly="" regulated="" by="" rna="" binding="" proteins,="" which="" coordinate="" splicing="" networks,="" through="" a="" 10-fold="" down="" regulation="" within="" the="" first="" two="" weeks="" after="" birth.="" the="" network="" will="" be="" identified="" using="" genome="" wide="" analyses="" of="" rna-seq="" to="" identify="" as="" transitions="" and="" uv-crosslinking="" and="" immunoprecipitation="" to="" identify="" celf="" target="" rnas="" in="" vivo.="" rna-seq="" will="" be="" used="" to="" identify="" splicing="" transitions="" separately="" in="" cm="" and="" cf="" during="" postnatal="" mouse="" heart="" development.="" our="" goal="" is="" to="" determine="" how="" alternative="" splicing="" is="" initiated="" and="" controlled="" in="" the="" early="" development="" of="" the="" heart="" —="" work="" that="" will="" lead="" to="" an="" improved="" understanding="" of="" cardiac="">