My laboratory uses neurobiological, high-throughput and bioinformatic approaches to characterize molecular mechanisms which control cell fate decisions of neural precursor cells in the developing and mature brain.
The assembly and maintenance of the mammalian brain by neural precursor cells (NPCs), are tightly regulated processes, which involve integration of intrinsic transcriptional programs with extrinsic information from the cellular microenvironment to ensure that the correct cell types are produced, at the right time, to establish functional circuits. Our major goal is to understand using a mixture of neurobiological, high-throughput and bioinformatic approaches how NPCs, sense their microenvironments, interpret this information and ultimately decide how to respond accordingly. Understanding how extrinsic cues control NPCs has the potential to inform novel therapeutic strategies aimed at activating these cells for repair following brain injury or disease. We are pursuing research in two major areas.
First, we have recently identified using single-cell genomics, a key ‘on/off’ switch which controls proliferation of radial precursor (RPs) cells in the developing brain by modulating their response to the cellular microenvironment. We aim to understand how this switch allows RPs to become ‘slow-dividing’ and persist into the adult brain to give rise to adult neural stem cells (NSCs). Leveraging a deep understanding of this ‘on/off switch,’ we aim to develop approaches to force this switch into the ‘off’ position thereby mobilizing NSCs following brain injury or disease.
Second, tissue resident stem cells such as adult NSCs are housed in specialize niche microenvironments with well defined cellular architectures. Spatial information is therefore critical in understanding the identity and sources of extrinsic cues which control NSC cell fate decisions. We are developing and applying methods to add spatial level information to transcriptomic data and thereby reveal the complexity of extrinsic regulation in the NSC niche.