Robert D. Nicholls, D. Phil.

Title
Professor
Department
Department of Pediatrics
Institution
Children's Hospital of Pittsburgh, University of Pittsburgh
Address
Rangos Research Center
3460 Fifth Avenue
City, State, Zip
Pittsburgh, PA 15213
Phone
(412) 692-7855
E-mail
Robert.Nicholls[at]chp.edu
Website
http://www.chp.edu/CHP/robert+nicholls+research+projects
Research Field
Genetics
Award Year
1991

Research

My lab uses mouse models and human patients to study the phenomenon of genome imprinting and it’s derangement in human disease. Prader-Willi and Angelman syndromes are disorders caused by a complex defect of genomic imprinting on chromosome 15. The imprinted SNRPN locus is a complex transcriptional unit that encodes the SNURF and SmN polypeptides as well as multiple non-coding RNAs. SNRPN is located within the Prader-Willi (PWS) and Angelman syndrome region that contains multiple imprinted genes, which are coordinately regulated by a bipartite imprinting center (IC). The SNRPN 5’ region co-localizes with the PWS-IC and contains two Dnase I hypersensitive sites, DHS1 at the SNRPN promoter, and DHS2 within intron 1, exclusively on the paternally inherited chromosome. My lab has identified cis- and trans-acting regulatory elements within the endogenous SNRPN 5’ region and allele-specific interactions with multiple regulatory proteins, including NRF-1, which regulates genes involved in mitochondrial and metabolic functions. Our goal is to characterize the complex mechanisms of disease related to these phenomena.