Mangano / Goto Lab

Projects

Lab Projects

Development of New Therapies for Neonatal Hydrocephalus

White matter injury and myelin loss are common pathological features of pediatric hydrocephalus and are thought to contribute to long-term neurological and psychological challenges. Our lab is dedicated to developing innovative, less invasive therapeutic strategies to improve outcomes for infants affected by this condition.

We use non-invasive, quantitative neuroimaging approaches, particularly diffusion tensor imaging (DTI), to characterize abnormal white matter integrity and to monitor recovery following treatment in children with hydrocephalus. These methods allow us to better understand disease progression and evaluate therapeutic efficacy.

In parallel, we employ animal models of neonatal hydrocephalus to test novel pharmacologic agents aimed at preserving healthy white matter development. We are also developing a new biologic therapy designed to regulate cerebrospinal fluid (CSF) production, with the goal of providing a one-time, minimally invasive treatment option for neonatal hydrocephalus.

Project Details

• Collaborators: Kenneth Campbell, PhD, Jason Tchieu, PhD, Diana Lindquist, PhD, Weihong Yuan, PhD, and Elliott Robinson, PhD.
• Funding: R61/33 (NINDS, R61NS138647), The Rudi Schulte Research Institute.

Molecular Mechanism in Non-Obstructive Pediatric Hydrocephalus in Mouse Genetic Mutants

Approximately 40% of pediatric hydrocephalus cases have an unknown cause. To address this critical knowledge gap, our lab studies genetic mouse and rat models that develop distinct forms of congenital, non-obstructive hydrocephalus. Our goal is to identify the molecular and cellular mechanisms essential for normal ventricular system development and CSF homeostasis.

We focus on newly identified models carrying mutations in cilia-related genes, including L1cam, to better understand how disruptions in cilia structure and function contribute to hydrocephalus. Through this work, we aim to define:

1. The role of motile cilia in neonatal brain development
2. Molecular pathways regulating CSF production, absorption, and circulation
3. Disease-causing gene mutations relevant to human congenital hydrocephalus

To accomplish these aims, we integrate mouse genetics, CRISPR/Cas9 genome editing, RNA sequencing, and exome sequencing with advanced imaging techniques such as diffusion tensor imaging and contrast-enhanced MRI.