Nancy B. Spinner, PhD
Professor, Depts of Pediatrics and Genetics

Genetics and Gene Regulation Program

Address

1007A Abramson Research Center
The Children's Hospital of Philadelphia
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318

Office tel.: 215-590-4177
Lab.: 215-590-3166
Fax: 215-590-3850
E-mail: spinner@mail.med.upenn.edu

Education

Brandeis University, B.A. (Anthropology), 1975

UC Berkeley, PH.D. (Genetics), 1984

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.

Search PubMed for articles

Description of Research

Our lab is interested in identifying genes that contribute to congenital disease. We have a long-standing 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.

A second project centers around identifying genomic abnormalities that are associated with fetal death. We are initiating a multi-pronged analysis of genomic abnormalities in a group of patients who died before or shortly after birth of unknown causes. We are using SNP array analysis and epigenomic analysis tools to identify abnormalities associated with fetal death.

We are also studying the Ring Chromosome 20, a rare cytogenetic abnormality that is associated with unusually severe seizures, to determine the mechanism by which this abnormal chromosome causes disease.

Recent Publications

Krantz ID and Spinner NB (2007) Novel microdeletion syndromes. Am J Med Genet Part C Semin Med Genet (in the press).

Warthen DM, Moore EC, Kamath BM, Morrissette JJD, Sanchez P, Piccoli DA, Krantz ID Spinner NB (2006) Jagged1 (JAG1) Mutations in Alagille syndrome. Hum Mut. 27:436-443

McDaniell R, Warthen DM, Piccoli DA, Sanchez-Lara PA, Pai A, Krantz ID, Spinner NB (2006) NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the Notch Signaling Pathway. Am J Hum Genet 79:19-17

Morrissette JJD, Medne L, Bentley T, Owens NL, Geiger E, Pipan M, Zackai EH, Shaikh T, Spinner, NB. (2005) A Patient with Mosaic Partial Trisomy 18 Resulting >From Dicentric Chromosome Breakage. Am J Med Genet 137A:208-212

Lu, F-M, Morrissette, JJD, Spinner, NB (2003) Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage. Am J Hum Genet 72:1065-1068

Lab

Rotation Projects

Contact Dr. Spinner for current rotation projects

Lab personnel:

Binita Kamath, MD Faculty candidate for masters in translational medicine
Rob Bauer-grad student
Laura Conlin, PhD-postdoctoral fellow
Brian Thiel, MS, Research Tech
Pedro Munoz, project coordinator
David Shin, undergraduate
Phoebe Cheng, undergraduate