Research

Autism Spectrum Disorder (ASD) is a range of neurodevelopmental disorders resulting in communication, learning, and behavioral deficiencies. Interestingly, human patients with ASD have altered synaptic density and microglia activation. Through a collaboration with the Kampmann lab at UCSF, we have an interest in investigating the functional role of ASD-risk genes identified from a CRISRRi-based screening from Teter et al., 2024 (Biorxiv). Using CRISPR mutants combined flow cytometer-based engulfment assay and scRNA sequencing technologies, we hope to gain a basic understanding of microglia-synaptic interactions in models of ASD.

As professional phagocytes of the brain, microglia are responsible for phagocytosing debris to maintain a healthy brain throughout life. While much is known regarding the “recognition” process of phagocytosis the mechanisms through which microglia efficiently digest and process material are less studied. We are interested in a family of lysosomal proteases known as cathepsins, which are enriched in microglia during development and a hallmark of disease-associated microglia (DAM) in multiple neurodegenerative diseases. Our work has found a role for cathepsin B mediating digestion of apoptotic cells in the developing brain of both zebrafish and mouse models (Under revisions: https://www.biorxiv.org/content/10.1101/2024.12.03.626596v1). Ongoing research is investigating the signaling mechanisms governing our phenotypes in cathepsin B mutant models.