Research topic: The lab focuses on studying issues related to early embryonic and developmental processes, genetic disorders and different aspects of cell therapy using our unique collection of PGD-derived human embryonic stem cells (hESCs).
Research methods: The Wolfe PGD-Stem Cell Lab focuses on studying issues related to early embryonic and developmental processes, genetic disorders and different aspects of cell therapy using our unique collection of PGD-derived human embryonic stem cells (hESCs). We derive human hESCs directly from affected embryos, following preimplantation genetic diagnosis (PGD). PGD is performed for couples at high risk of transmitting a genetic defect to ensure the birth of a healthy baby. Following in vitro fertilization and PGD, the affected embryos that are normally discarded are used to establish hESC lines carrying the genetic disease. These cells are now a valuable tool for studying the pathophysiology of these diseases in humans. See list of projects in our website. One of our major projects involves studying Fragile X syndrome (FXS) – the most common form of inherited intellectual disability. Using FXS affected hESCs we gained novel insight into the molecular mechanisms responsible for the development of FXS (Eiges et al., and Ben-Yosef, Cell Stem Cell 2007). We showed that the CGG expansion alone is not sufficient for FMR1 gene silencing. Following the course of differentiation of these cells into functional neurons we could further identify aberrant molecular functions and cell fate decisions that may underlie the disease (Telias et al 2013). We are now studying the molecular and cellular mechanisms by which FMR1 inactivation impairs neurogenesis, leading to the characteristic FXS phenotype of cognitive impairment. This will enable the identification of new therapeutic targets for FXS, whereupon our human FXS neurons can also be used as a reliable in-vitro drug screening platform.
Techniques used in our lab: in vitro neural differentiation of human embryonic stem cells, CRISPR/Cas9 genome engineering, next generation sequencing, direct cell fate conversion, advanced cloning and molecular biology techniques.