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Research
How neurons build the proteins that let the brain learn
We study protein synthesis at the synapse: how experience changes what neurons translate, and how that process goes wrong in neurodevelopmental disorders. We work in mouse models and in living human cortex.
Our research questions are being investigated in multiple neural circuits using biochemical, electrophysiological and systems-level approaches. We are studying these basic biological questions using human and animal models. It is our belief that identifying the mechanisms that go awry in these models will simultaneously address fundamental questions of synaptic function, and provide a better understanding of autism and ID.
TRAP-seq identifies novel targets in FX
tdTom filled TRAP neurons
Autoradiograph WT versus Fmr1-KO
TRAP-seq identifies novel targets in FX
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Current projects include:
Human brain slices
Human cortex differs from mouse cortex in its cell types, circuits and synaptic dynamics. How do genetic drivers of NDD impact human cortical circuits? To answer this, we keep slices of donated human cortex alive and active in culture for weeks, which lets us model genetic disease directly in human neurons and test therapies against it (Singh*, Abbaspoor*, Chung*, Heinrich*, et al., Biorxiv, 2026).
By performing single-cell RNA-seq (scRNA-seq), we can compare the concordance between human slice models, patient populations, and mutant mouse models. Patch-clamp electrophysiology tells us how function is impacted.
The way NDD gene disruption impacts human cortical circuits is not known. In collaboration with Jordan Farrell, we are performing 2p functional imaging to identify augmented activity.
Gene therapy
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual (ID), and is characterized by high rates of ADHD, autism and epileptiform activity in early childhood. The strong negative correlation between ID severity and FMRP expression suggests a gene therapy approach could be a promising therapeutic strategy. We are testing this possibility using mouse and human models, investigating not just does it work, but how it works (Maio et al., BioRXiv, 2026).
Proteostasis
We previously showed that protein degradation by the ubiquitin proteasome system (UPS) is elevated in FXS neurons, and this is coupled to accelerated protein synthesis (Louros et al., Neuron, 2023). We are investigating how this feedback mechanism works in human and mouse, how is it contributing to hyperexcitability, and whether it is a common disruption in multiple NDDs.
SYNGAP1
Several NDD genes encode regulators of synaptic protein synthesis, including SYNGAP1. We are investigation how reduction of SynGAP alters synaptic function and results in behavioral aspects of impaired risk-assessment and attention.
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