A5111148684- Congenital gastrointestinal and neural anomalies
- Gastrointestinal motility and disorders
- Viral gastroenteritis research and epidemiology
- Lysosomal Storage Disorders Research
- Infant Nutrition and Health
- Gastroesophageal reflux and treatments
- Glycogen Storage Diseases and Myoclonus
- Intestinal Malrotation and Obstruction Disorders
- Child Nutrition and Feeding Issues
Children's Hospital of Philadelphia
2024-2025
University of Pennsylvania
2025
Hirschsprung's disease is defined by the absence of enteric nervous system (ENS) from distal bowel. Primary treatment "pull-through" surgery to remove bowel that lacks ENS, with reanastomosis "normal" near anal verge. Problems after pull-through are common, and some may be due retained hypoganglionic (ie, low ENS density). Testing this hypothesis has been difficult because counting neurons in tissue sections unreliable, even for experts. Tissue clearing 3-dimensional imaging provide better...
Children with neurodegenerative disease often have debilitating gastrointestinal symptoms. We hypothesized that this may be due at least in part to underappreciated degeneration of neurons the enteric nervous system (ENS), master regulator bowel function. To test hypothesis, we evaluated mouse models neuronal ceroid lipofuscinosis type 1 and 2 (CLN1 CLN2 disease, respectively), lysosomal storage disorders caused by deficiencies palmitoyl protein thioesterase-1 tripeptidyl peptidase-1,...
CLN3 disease causes profound neurological deficits in affected children, but less well recognized are a variety of peripheral neuromuscular and gastrointestinal problems. We hypothesized that addition to central nervous system (CNS) degeneration, deficiency may also directly affect neuronal and/or glial cell populations the rest body. Therefore, we examined enteric Cln3Δex7/8 mice. There was no overt sciatic nerve axon loss or demyelination mice, significant terminal Schwann cells (tSCs) at...
Epigenetic regulatory mechanisms are underappreciated, yet critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in ENS lineage caused severe postnatal bowel dysfunction early death Tyrosinase-Cre Bap1fl/fl mice. Bap1-depleted appeared normal neonates; however, by P15, Bap1-deficient neurons were largely absent from small large intestine Bowel motility became markedly abnormal with disproportionate cholinergic...