Forrest Lab
Principal Investigator: Marc Forrest
Institution: Northwestern University (Chicago, IL)
Primary Subfield: Neuroscience
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
ABSTRACT Alternative splicing vastly expands the functional repertoire of genes, and is especially important during human synapse development. Human synapses have unique structures and compositions, but the mechanisms involved in their development remains elusive. Investigations into human-specific aspects of synaptic machinery have revealed a critical role for Rho guanine nucleotide exchange factor (GEF) signaling. TRIO is a large multi-domain RhoGEF with essential roles in neuronal and synaptic development. TRIO is also a genome-wide significant risk factor for neurodevelopmental disorders and glutamatergic synapses have been implicated by genomic, neuropathological, and functional studies as key sites of pathogenesis. Individuals with pathogenic TRIO variants are characterized by intellectual disability, developmental delay, and seizures. The TRIO gene produces multiple distinct isoforms that differentially incorporate TRIO’s functional domains including two GEF domains that having opposing functions on the actin cytoskeleton. Thus, precise control of TRIO’s GEF domains through expression and localization of isoforms is paramount for its function. However, the diversity and expr…
Active NIH Awards
- 1R21NS148969-01: Diversity and function of TRIO isoforms during human synapse development (2026)
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