We aim to understand a long standing question in biology: What molecular features make us uniquely human and how do these function?
We use a multidisciplinary approach (including genomics, mouse genetics, and primate iPSCS and organoids) to uncover and investigate the genetic changes that underlie human-specific brain development and function. We have been focused on noncoding regulatory sequences called human accelerated regions, or HARs, which have acquired changes specific to the human lineage. Our work has identified several HARs which act as transcriptional enhancers in the developing brain. We then study the activity differences and functional impact of these enhancers upon brain development.
Our first study describing one of these loci, HARE5, was published in Current Biology and was featured in multiple news outlets! Please see our reviews in Bioessays, Current Opinion in Neurobiology to hear more about this exciting topic. Learn about this work on evolutionary-important enhancers published in Current Biology, with an interview with Debby on NPR!
Our recent study in Nature uses mouse models and primate iPSCs to mechanistically understand how HARE5 influences neural progenitors. This work was also featured in a preview in Nature. We show that HARE5 fine-tunes radial glia potency and neurogenesis to impact cortical expansion and function. This enhancer directly increases brain size and neuron number by modifying the ability of neural stem cells of the brain, called radial glia, to make neurons. In collaboration with Ewoud Schmidt’s group we show this impacts functional connectivity in the brain. Our study leverages mouse models and human and chimpanzee stem cells to manipulate this specific enhancer and directly tie it to progenitor function.
We continue to investigate molecular regulation of cortical evolution using mouse, human, and other primate models.
