Project Grant R21NS147341

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, awarded the University of Illinois $225,439 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to develop and validate animal models of hypothalamic hamartoma.

The project uses novel viral-transgenic strategies and CRISPR gene editing to create sporadic, mosaic disruption of sonic hedgehog signaling in mice with selective hypothalamic targeting, replicating the molecular pathology observed in human hypothalamic hamartoma lesions. Research aims include determining how neonatal mosaic sonic hedgehog signaling disruption in the hypothalamus affects seizure susceptibility and epileptogenesis in mice, and generating and validating novel adeno-associated virus vectors driving CRISPR-mediated insertion of hypothalamic hamartoma-associated mutations into key components of the sonic hedgehog signaling pathway. The work addresses the absence of established animal models for hypothalamic hamartoma, a non-cancerous brain tumor affecting approximately one in 200,000 children and frequently presenting with refractory gelastic or dacrystic seizures, central precocious puberty, cognitive deficits, and psychiatric symptoms.

Performance occurs in Urbana, Illinois. The period of performance runs from September 1, 2026 through July 31, 2028. This is a Project Grant, a form of assistance funding under NIH's standard peer-review process for extramural research.