1. Great ape organoids: Complex, multi-lineage, 3D organ-like tissues (so called “organoids”) can be generated using pluripotent stem cells from human, chimpanzee and other great apes. We are using single-cell genomics on human, chimp, and other great ape organoids to uncover features that are unique to human developmental programs.
2. Neandertalized cells: We are working with other groups in the department to revert modern human DNA in human stem cells back to the ancestral state to create “Neandertalized” stem cell lines. We will use these cells to understand the physiological impact of genetic change on the modern human lineage.
3. High-throughput cellular phenotyping: We are developing high-throughput strategies to use CRISPR-Cas9 editing in combination with single-cell transcriptomics and confocal imaging to understand how genetic change affects neuron and hepatocyte cell biology.
4: Organ malformation: We are using 3D organoids to understand how rare human genetic diseases perturb gene networks controlling human development, with particular focus on the cortex and liver.