Description of Research Expertise

Research Interests
Human Genetics, Notch signaling in human disease, Alagille syndrome, human disease gene identifcation by mapping deletions.

Key words: Jagged1, Notch Signaling, Alagille syndrome, chromosome deletions.

Description of Research
Our lab is interested in identifying genes that contribute to congenital disease, with a particular interest in the genes of the Notch Signaling Pathway. We have now identified mutations in both Jagged1 and NOTCH2 as a cause of the multi-system disorder Alagille syndrome. Alagille syndrome affects multiple organ systems, but the systems affected, and the severity of disease varies greatly both within and between families, and we are working to identify the genetic factors that influence this variation. We are currently studying the disease associated mutations in JAG1 and NOTCH2 in tissue culture, to determine the mechanism by which Notch signaling is perturbed; and we are using genetic epidemiologic approaches to identify genes that modify the severity of the phenotypes seen in patients. We are focusing on the liver, cardiac and renal aspects of this multi-system disorder.

Another project in the lab concerns the molecular mapping of a variety of chromosomal disorders (primarily deletions), in order to map the genes that are missing, and correlate these with patient phenotypes. This approach is aimed at identifying candidate genes for various malformations.

Rotation Projects for 2006-2007
1. Quantitative JAG1/NOTCH2 levels and severity of renal, cardiac disease in Alagille syndrome
2. Functional consequences of novel mutations (NOTCH1, NOTCH2, JAG1)
3. Mapping subtelomeric abnormalities by array CGH to identify disease genes

Lab personnel:
Rob Bauer--grad student
Andres Greco, MD Postdoctoral Fellow
Ayanna Laney, PhD Postdoctoral Fellow
Jen Miller-Soosaar, PhD Postdoctoral Fellow
Brian Thiel, MS Technician