Hebner, Yuki

Yuki is in the Gene Regulation, Epigenomics and Transcriptomics home area of the MBIDP.  She received a B.A. and an M.A. in Molecular Biology and Biochemistry from Wesleyan University.  She joined the CMB training program in 2019. 

Mentor: Dr. Luis de la Torre-Ubieta

Research project:

The molecular mechanisms underlying human corticogenesis are not well characterized, but critically important to understanding the development of our complex cognitive abilities and how the dysregulation of these mechanisms can lead to intellectual impairment and neuropsychological disease. Of particular interest is how neocortical progenitor cells progress into various cell fate lineages without the guidance of sequence-templated changes. The activity of cis-regulatory elements and their corresponding transcription factors (TFs) are thought to play a pivotal role in modulating the transcriptional programs that drive corticogenesis. Further, changes in chromatin conformation are required to bring distal enhancers into physical proximity with their corresponding promoters, and these regulatory elements provide binding sites for TFs.

A previous lab effort to profile transcriptional programs that are differentially expressed across neocortical cell types identified several TFs that are enriched in radial glia-progenitor cells that are located in the germinal zone (GZ) of the neocortex and mature into cortical plate (CP) neurons. Laminae-specific expression of these TFs suggests participation in corticogenesis; additionally, we have discovered putative enhancers of these TFs that display differential accessibility between GZ neural progenitors and CP neurons. These studies collectively lead to my hypothesis that the modulation of specific TF activities by distal enhancers and chromatin remodelers contributes to proper neural development, and by extension, that TF-related dysregulation of corticogenesis can lead to neurological disorders. I am using CRISPR-interfernence to disrupt chromatin structure at candidate cis-regulatory regions in human neural progenitor cells, and various high-resolution genomic tools to study consequential changes in the interplay between chromatin accessibility (ATAC-seq), chromatin conformation (Hi-C), transcription (scRNA-seq), and chromatin remodeler binding (ChIP-seq) that may impede neocortical deveopment. These methods will allow me to comprehensively explore the relationship between genome organization and gene regulation, and apply these findings to elucidate the epigenetic mechanisms that orchestrate human brain development.