- Professor of Pediatrics at University of Pennsylvania School of Medicine (2013– present)
- Professor of Human Genetics in Pediatrics at the Children's Hospital of Philadelphia (2004 – 2009)
- Professor of Pathology and Laboratory Medicine at the Children's Hospital of Philadelphia (2010– present)
- Professor of Genetics at University of Pennsylvania School of Medicine (2004– present)
- Assistant Professor of Genetics at University of Pennsylvania School of Medicine (1991 – 1998)
- Assistant Professor of Human Genetics in Pediatrics at the Children's Hospital of Philadelphia (1991 – 1998)
- Associate Professor of Genetics at University of Pennsylvania School of Medicine (1998 – 2004)
- Associate Professor of Human Genetics in Pediatrics at the Children's Hospital of Philadelphia (1998 – 2004)
CytoGenomic Diagnostics, copy number variation, cytogenetics
Etiology of pediatric disease, molecular analysis of Alagille syndrome (currently identifying modifiers of liver disease severity), genetic basis of biliary atresia, molecular analysis of ring chromosome 20.
Human Genetics, Notch signaling in human disease, Alagille syndrome, Biliary Atresia, SNP array analysis, copy number variation, human disease gene identification by mapping deletions, Ring Chromosome 14, Ring Chromosome 20, Genome wide association studies, next-generation sequencing, chromosomal analysis,
Key words: JAG1, NOTCH2, Notch Signaling Pathway, Alagille syndrome, Biliary Atresia, Ring Chromosomes, Ring Chromosome 14, Ring Chromosome 20, Whole Exome Sequencing (WES), Whole Genome Sequencing (WGS), Bioinformatics, Induced pluripotent stem cells
Description of Research
Our lab is interested in identifying genes that contribute to congenital disease. We have a long-standing interest in Alagille syndrome, a genetic disorder that affects the heart and liver. We have demonstrated that this disorder is caused by two genes in the Notch Signaling Pathway, and have continued to study the effect of these mutations, seeking to understand the clinical spectrum of defects in these disorders. Currently, we are looking to identify the genetic factors that modify the clinical variation present in this disease.
In addition to our work on Alagille syndrome, we are funded to investigate the genetic susceptibility to Biliary Atresia (BA). Various research efforts are underway, including GWAS and whole exome sequencing of individuals and trios. Using these techniques, we are exploring several genes that may contribute to the etiology of BA.
We are working on understanding the molecular basis of the clinical features observed in patients with Ring Chromosome 14 Syndrome and Ring Chromosome 20 Syndrome. To achieve this goal, we are exploring a number of different research strategies, including iPS cell work. By characterizing the rings, we hope to identify the mechanism by which ring chromosomes lead to human disease and the characteristic seizure phenotype.
In colloboation with Dr. Ian Krantz, we lead a program project grant to test the applications of whole exome sequencing to 5 pediatric disorders, as well as to explore the ethical and psychosocial implications of this work.
Debbie McEldrew - Research Associate
Jason Mills, Ph.D. ? Research Associate
Christopher Grochowski ? Senior Research Technician
Ramakrishnan Rajagopalan ? Bioinformatics Specialist
Alexandra Falsey ? Clinical Research Coordinator
- Ph.D., Genetics, University of California at Berkeley/San Diego State (1984)
- B.A., Anthropology, Brandeis University (1975)
- Shaikh TH, Gai X, Perin JC, Glessner JT, Xie H, Murphy K, O'Hara R, Casalunovo T, Conlin LK, D'Arcy M, Frackelton EC, Geiger EA, Haldeman-Englert C, Imielinski M, Kim CE, Medne L, Annaiah K, Bradfield JP, Dabaghyan E, Eckert A, Onyiah CC, Ostapenko S, Otieno FG, Santa E, Shaner JL, Skraban R, Smith RM, Elia J, Goldmuntz E, Spinner NB, Zackai EH, Chiavacci RM, Grundmeier R, Rappaport EF, Grant SF, White PS, Hakonarson H.. High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications.. Genome Research. Vol 19(9) . 2009 July:1682-90.
- DeScipio C, Spinner NB, Kaur M, Yaeger D, Ambrosini, A, Hu S, Shan S, Conlin LK, Krantz ID, Riethman, H. Fine-Mapping Subtelomeric Deletions and Duplications by Comparative Genomic Hybridization in 42 Individuals.. Am J Med Genet A.. Vol 146. 2008:730-739.