Led by Jennifer M. Kalish, MD PhD researchers in the Kalish Laboratory are focused on understanding the molecular and epigenetic mechanisms that contribute to the development, epigenetic mosaicism and increased predisposition to cancer that is characteristic of pediatric patients with rare imprinted gene disorders including Beckwith-Wiedemann syndrome (BWS) and Russell-Silver syndrome (RSS). The long term goal of the research conducted in this laboratory is to develop new diagnostic/prognostic tools and interventional strategies to improve medical outcomes for patients with BWS, RSS and related imprinted gene disorders.
Ongoing research in the Kalish laboratory is focused on elucidating the underlying genetic and epigenetic mechanisms that contribute to the increased cancer risk for children with BWS. Using pluripotent stem cell lines from patients with BWS and BWS mouse model, members of the Kalish Laboratory are studying the cellular pathways that may contribute to the increased risk/incidence of cancer that is characteristic of many patients with BWS.
Other studies in the Kalish Laboratory are directed towards understanding the epigenetic regulatory mechanisms that contribute to the phenotypic mosaicism that is characteristic of many human imprinting gene disorders including RSS. Members of the Kalish Laboratory, in collaboration with the Raj and Bartolomei laboratories at the University of Pennsylvania, developed and applied a new fluorescence hybridization technique that has been used to show striking single-cell molecular heterogeneity in mouse models of RSS. These results suggested single-cell molecular heterogeneity may underlie the epigenetic mosaicism frequently observed in human imprinting gene disorders.
Future studies in the Kalish Laboratory will continue to focus on gaining greater insights into the molecular and epigenetic mechanisms that contribute to the development, cancer predisposition and epigenetic mosaicism commonly observed in patients with human imprinting gene disorders.