Nora I. Engel, PhD
Assistant Professor, Fels Institute for Cancer Research and Molecular Biology
Associate Professor, Biochemistry
Department of Biochemistry
Fels Institute for Cancer Research and Molecular Biology
My research concentrates on understanding the interactions, mechanisms and epigenetic modifications of DNA sequences that regulate transcription. As a model, we focus on a multigene region that exhibits genomic imprinting. “Imprinted” genes are consistently expressed from only one of the two parental copies. It is believed that imprinted genes are marked with a memory of their parental origin, and that the marks are reversible chemical or structural modifications of the DNA occurring during development of each germline. This type of modification is termed “epigenetic” and allows the parental alleles to be distinguished. The fact that imprinted genes are only active from one allele means that any perturbation in their expression is dominant. In fact, proper regulation of imprinted genes is crucial and alteration of their status in humans can lead to both genetic diseases and cancer.
The Cdkn1c domain is a group of imprinted genes including at least 8 maternally expressed genes and one paternally expressed long non-coding RNA with silencing activity. Alterations of imprinting in this domain have been found in Beckwith-Wiedemann syndrome, an overgrowth disorder with predisposition to cancer. Also, mutations in Cdkn1c, a cyclin-dependent kinase inhibitor, have been documented in human cancers.
The research in my lab explores the molecular mechanisms that regulate transcriptional features of imprinted regions, including epigenetic features and three-dimensional conformations, by an interdisciplinary approach combining in silico, in vitro and in vivo technologies to understand the interactions of regulatory DNA sequences.