Overview
My research focus aims to understand how gene-regulatory elements control gene expression in mammals, as it relates to the genetic basis of development, evolution and disease. To study the function of enhancers, my approach includes three key components (see figure below).
First, I will identify putative enhancers from comprehensive genomic datasets and GWAS data. Secondly, the in vivo function of these enhancer candidates will be characterized using a combination of mouse genetics and functional genomics techniques. In the final phase, by integrating this functional information, I will use enhancers as tools to manipulate phenotype, such as altering morphology and developing new therapeutic approaches.
Projects
Systematic evaluation of variants in non-coding regions associated with diseases (abnormal pregnancy and craniofacial birth defects)
In this project, we will leverage the unique aspects of the in vivo MPRA I developed during my K99/R00 projects to functionally characterize gene regulatory elements involved in placental and craniofacial development. The goal of this project is to identify variants that lead to diseases and to understand their pathogenic mechanisms.
Currently we are especially interested in GWAS variants associated with preeclampsia and craniofacial microsomia.
Identifying tooth injury responsive enhancers
The rodent incisor, unlike human teeth, grows throughout the animal’s life and can serve as an exceptional regeneration model. Adult mouse incisors, once clipped, can fully regenerate within two weeks. We will identify the enhancers involved in this process.
Making bat-mice
Enhancers are emerging as major modifiers of skeletal structures, known to play crucial roles in limb and craniofacial morphology. We hypothesized that the enhancers contribute to the diverse limb morphology in mammals through controlling the tool kit genes that are broadly conserved in mammals. We will prove this idea using CRISPR/Cas9 genome editing in mice.
