The overall goal of the Zhao laboratory is to model and treat human genetic diseases using stem cells. Stem cells have the capacity to generate identical daughter stem cells (self-renewal) and to differentiate into terminally differentiated cell types (pluripotency or multipotency), therefore serving as a powerful in vitro tool to study normal and diseased human embryo development and a potential donor tissue source for cell therapy. The current research of the Zhao Laboratory is focusing on the following areas:
1.The basic biology of pluripotent stem cells (PSCs)
We are interested in understanding the underlying mechanisms that regulate self-renewal and differentiation of human and mouse and PSCs.This knowledge is critical to design novel methods to generate disease-relevant cell types for disease modeling and stem cell therapy. We are interested in the roles of microRNAs, the small non-coding RNAs critical for post-transcriptional regulation, in self-renewal, lineage differentiation, and somatic cell reprogramming of human and mouse PSCs.
2. Model human congenital diseases using pluripotent stem cells
The defects of congenital diseases usually occur during human embryo development, which is inaccessible for experimentation. Although animal models have played indispensable roles in understanding human diseases, they often fail to mimic features unique to humans. Human induced pluripotent stem cells (hiPSCs) generated from patient cells (e.g., skin fibroblasts, peripheral blood), which carry all genetic abnormalities of the disease, serve as a novel in vitro model to recapitulate the diseased embryo development. Currently, we are modeling monogenic congenital diseases such as Cystic Fibrosis (CF) and Tay-Sachs disease (TSD) and diseases with chromosomal fragment deletions such as DiGeorge Syndrome (DGS). We also evaluate the efficacy of potential gene therapy methods using hiPSC disease models.
3. Model human cancer using pluripotent stem cells
Brain tumors (gliomas) are incurable and are among the most fatal tumors in adults. We have established hiPSCs from primary glioma cells. We are in the process of establishing an in vitro model of gliomagenesis using the glioma cell-derived hiPSCs. We expect that this model will facilitate the identification of novel drug targets and the development of new therapies to treat gliomas.
