Innovative Tools & Techniques

Major current tool development research questions:

Can we develop novel nanoscale imaging techniques to map protein localization at individual synapses?

Can we model aspects of human brain circuitry using human-derived neurons and glia?

Can we uncover human-specific brain connectivity pathways using new gene discovery platforms?

Nanoscale imaging of the nervous system. Fine-scale molecular architecture is crucial for nervous system function. To enable rapid and robust visualization of nanoscale structures, we developed RAIN-STORM—a rapid, scalable nanoscopic imaging method that enhances three-dimensional visualization of subcellular targets in tissue at depth. RAIN-STORM enables high-throughput studies of nanoscopic targets within tissue, providing insights into cellular architecture. We are now extending these studies to PAINT based imaging.Models of human eye-brain connectivity. Retinal ganglion cells (RGCs) are essential conduits for transmitting visual information to the brain. These cells target distinct retinorecipient areas, and this precision is crucial for visual processing. Functional or anatomical defects in RGC connectivity with their post-synaptic targets is a key feature of RGC-related visual diseases, including glaucoma, but the mechanisms by which human RGC form and maintain brain inputs are unknown. To address these questions, we are developing human eye-to-brain connectivity platforms that combines polarized human RGCs, microfluidics, region-specific post-synaptic targets, and synapse and circuit readouts to investigate the development and maintenence of the human visual system.

Comparative omics approaches. Complementing these approaches, we also developed STATE-seq. This method that allows for the isolation of high-quality RNA from flow-cytometry sorted cells following fixation and antibody staining. STATE-seq is particularly compelling because it leverages well-characterized intracellular antibodies to distinguish cells of specific types and states, enabling direct transcriptional comparisons among them.