Fall 2025 Grantee Highlight:
Brady J. Maher

Brady J. Maher, PhD

Lead Investigator, Lieber Institute for Brain Development

Schizophrenia (SCZ) is a complex genetic disorder characterized by a broad range of positive, negative, and affective symptoms, as well as cognitive deficits that vary widely among individuals. Current treatments primarily work by blocking dopamine signaling, which can reduce positive symptoms such as hallucinations and delusions in some patients. However, these therapies often cause significant side effects and rarely improve negative symptoms or cognition. As a result, there remains a critical need for more effective and personalized interventional approaches.

The Maher Lab is using human induced pluripotent stem cells (hiPSCs) derived from individuals with SCZ and neurotypical controls to model the disorder and identify underlying pathophysiology, disease mechanisms, and therapeutic targets. Their recent work has revealed SCZ‑associated alterations in voltage‑gated sodium channel (VGSC) function in hiPSC‑derived human neurons. Importantly, these electrophysiological differences correlate with the clinical symptoms of the patients from whom the cells were derived, underscoring their relevance and potential for individualized treatment strategies.

By integrating several cutting‑edge technologies (hiPSC‑derived neurons, automated high‑throughput electrophysiology, CRISPR/Cas9 genomic editing, and proteomics), the Maher Lab’s project will focus on identifying specific VGSC isoform(s) and functionally related proteins that could serve as targets for the development of new therapeutics for SCZ.