Our laboratory focuses on understanding how pluripotent stem cells become neurons, in vitro and in the brain. We are interested in the basic regulatory mechanisms establishing and refining this lineage, as well as in potential clinical applications using embryonic stem cell-derived material.
Making neural stem cells from embryonic stem cells
Based on their therapeutic potential, there is great interest in producing neural stem cells, as well as neurons and glia, from embryonic stem cells (ESCs). Neural stem cells form rosettes in culture, a structure reminiscent of the neural tube. We are currently focusing on the formation of this structure, the establishment of cell polarity within the rosette, the role of primary cilia as a site of signaling, and the specification of neuronal subtypes.
Differentiation of embryonic stem cells into GABAergic inhibitory interneuron progenitors
Current studies are examining the production of GABAergic neural progenitors from both mouse and human embryonic stem cells for in vitro characterization and in vivo transplantation studies in a mouse model of temporal lobe epilepsy in conjunction with the Naegele and Aaron labs at Wesleyan University.
Transcriptome analysis using high throughput mRNA sequencing
We are using transcriptome analysis to elucidate the differences between generic embryonic stem cell derived neural progenitors versus neural progenitors treated with factors like sonic hedgehog to induce a ventral forebrain GABAergic inhibitory interneuron fate. This work is done in collaboration with the Gravely lab at the University of Connecticut Health Center.
Long-term co-culture of embryonic stem cell derived GABAergic progenitors with mouse cortical astrocytes
We are investigating the terminal differentiation potential of mouse and human embryonic stem cell derived GABAergic interneuron progenitors by culturing with mouse cortical astrocytes and hippocampal cells.
Migration of mouse and human embryonic stem-cell derived neural progenitors and their association with the host vasculature
Embryonic stem cell-derived neural progenitors transplanted to the hippocampus can hitch a ride on the host vasculature and travel some distance from the initial site of injection. We are using hippocampal slice culture and endothelial cell adhesion assays to determine the molecular players involved in this interaction.