Sumantra Chatterjee

My lab investigates developmental disorders of neural crest cells that affect both the central and autonomic nervous systems. We focus on Hirschsprung disease (HSCR), which disrupts the enteric nervous system, Familial Dysautonomia (FD), which primarily impacts the peripheral nervous system, and Mowat-Wilson Syndrome (MWS), which affects the central nervous system. Notably, many patients with FD and MWS also present with HSCR, suggesting that shared molecular pathways may contribute to disease pathogenesis across these disorders.

Our Research Focus We aim to uncover the genetic and cellular mechanisms driving these neurocristopathies by integrating genomics, stem cell models, and gene-editing technologies. Our work is structured around three key themes:

1. Genetic Changes underlying Neurocristopathies: We use whole-genome and whole-exome sequencing to identify disease-associated variants and understand the genetic complexity of HSCR, FD, and MWS. By mapping modifier genes and genetic interactions, we aim to explain the variable penetrance and phenotypic diversity observed in these disorders. 2. Connecting Cell-Type-Specific Responses Across Disorders: To explore how disease variants influence nervous system development, we generate enteric neurons from human embryonic stem cells (hESCs) and patient-derived induced pluripotent stem cells (iPSCs). This approach allows us to catalog cellular defects linked to patient-specific mutations, offering insight into why some individuals escape aganglionosis while others do not. 3. Cellular Therapeutics & Gene Repair: Neural crest cells possess remarkable regenerative potential, making them a promising target for stem-cell-based therapies. We leverage CRISPR-based genome editing to model patient-specific mutations in iPSCs and explore strategies to repair these defects, with the long-term goal of improving phenotypic outcomes and therapeutic interventions. Our Vision By integrating genomics, stem cell biology, and gene-editing technologies, our lab seeks to bridge fundamental discoveries with potential therapeutic strategies, ultimately improving our understanding and treatment of neurocristopathies.