Mangano Lab

Current Projects

White matter damage and myelin loss, common pathological features in pediatric hydrocephalus, are believed to be associated with neurologic and psychological sequelae. In collaboration with Dr. Weihong Yuan (Radiology) and Kenneth Campbell (Developmental Biology), we have been studying non-invasive quantitative methods to evaluate abnormal white matter integrity and post treatment recovery in children with hydrocephalus using diffusion tensor imaging (DTI). We found variable patterns DTI abnormalities in different white matter regions in children with hydrocephalus [3,6] > Yuan W. 2013, Sun M. 2012 and in a rat neonatal and infantile model of hydrocephalus [2,10] > Yuan W.2012, 2010. Currently, we are studying the effect of hydrocephalus on neural stem cells and oligodendrocyte precursor cell proliferation, migration, and differentiation in the rat model. Histopathology and CSF data obtained before and after surgery will help determine acute and/or long-term surgical outcomes in white matter development and injury recovery in hydrocephalus.

Collaborator: Weihong Yuan (Radiology) and Kenneth Campbell (Developmental Biology)
Funding: Longitudinal DTI study in children treated for congenital hydrocephalus
Co-Principal Investigator: National Institutes of Health, R01NS066932-04 Co-PIs: Weihong Yuan and Francesco Mangano

DTI index map for rat model of infantile hydrocephalus (top) and controls (bottom) Fluorescent immunohistochemistry for Olig2 (red) and BrdU (green) in rat corpus callosum

DTI index map for rat model of infantile hydrocephalus (top) and controls (bottom).

Fluorescent immunohistochemistry for Olig2 (red) and BrdU (green) in rat corpus callosum.

 

About 40% of the pediatric hydrocephalus has unknown etiology. Using mouse and rat genetic models that develop different types of congenital hydrocephalus, we aim to understand essential molecular and cellular mechanisms for the normal ventricular system development and function.

In collaboration with Drs. Rolf Stottmann (Human Genetics), Kenneth Campbell (Developmental Biology), and Diana Lindquist (Radiology), we are currently studying new mouse and rat hydrocephalus models with genetic mutations in cilia genes, the L1cam gene, and etc. We aim to identify:

  1. The function of motile cilia in the neonatal brain development
  2. Molecular mechanisms for the CSF production/absorption/circulation system
  3. Responsible gene mutations for human congenital hydrocephalus, utilizing molecular biology techniques such as mouse genetics, CRISPR/Cas9 genome editing system, RNA-seq analysis, and exome sequencing and advanced imaging tools including diffusion tensor imaging and contrast-enhanced MRI.

Collaborators: Rolf Stottmann, PhD, Kenneth Campbell, PhD, Diana Lindquist, PhD

We plan to launch multidisciplinary research projects around human congenital hydrocephalus as well as tuberous sclerosis complex.