Research Expertise

Research Interests
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.

Lab Personnel:
Debbie McEldrew - Research Associate
Jason Mills, Ph.D. – Research Associate
Christopher Grochowski – Senior Research Technician
Ramakrishnan Rajagopalan – Bioinformatics Specialist
Alexandra Falsey – Clinical Research Coordinator

Clinical Expertise

CytoGenomic Diagnostics, copy number variation, cytogenetics

Itmat Expertise

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.

Graduate Groups

Cell and Molecular Biology
Genomics and Computational Biology

Education

B.A. (Anthropology), Brandeis University, 1975
Ph.D. (Genetics), University of California at Berkeley/San Diego State, 1984

Specialty Certification

American Board of Medical Genetics
Ph.D. Medical Genetics and Clinical Cytogenetics, 1987

Postgraduate Training

Fellow in Genetics, The Children's Hospital of Philadelphia, 1984-1986

Awards and Honors

Dean's List, Brandeis University, 1972-1975
Mary Elizabeth Rennie intramural award for research on epilepsy, University of California, Berkley, 1984-1985
Recipient Florence R.C. Murray Fellowship, University of Pennsylvania School of Medicine, 1992-1993
Ethel Brown Foerderer Fund Fellow, University of Pennsylvania School of Medicine, Class of 1999 Excellence in Teaching Award, 1995-1997
University of Pennsylvania School of Medicine, Class of 1999, Excellence in Teaching Award, 1996
University of Pennsylvania, Class of 2000, Excellence in Teaching Award, 1997
Dean's Award for Excellence in Basic Science Teaching, University of Pennsylvania School of Medicine, 1997
Klaus and Mary Hummeler Endowed Research Prize, 1999
Ethel Brown Foerderer Fund Fellow, 2002
John Morgan Society, University of Pennsylvania School of Medicine, 2004
Keynote Speaker, Women in Medicine Dinner, University of Pennsylvania Department of Pathology, 2007
Faculty Mentor Award, The Children's Hospital of Philadelphia, 2009
International System for CytoGenomic Arrays (ISCA) Steering Committee, 2009
Evelyn Willing Bromley Endowed Chair in Pediatric Pathology, 2011
Board of Scientific Counselors, National Institute on Deafness and Other Communication Disorders (NIDCD), 2015

Memberships and Professional Organizations

American Society of Human Genetics (ASHG), 1980 - Present
Ad Hoc Reviewer for National Cancer Institute; Workshop Review Panel, 1992 - 1992
American College of Medical Genetics, 1993 - Present
Ad Hoc Reviewer of abstracts for presentation at the 43rd Annual Meeting of the American Society of Human Genetics, 1993 - 1993
American College of Medical Genetics, 1993 - Present
US Army Medical Research and Material Command-Peer Review Scientist for Breast Cancer Study Section, 1995 - 1995
Wellcome Trust, Ad Hoc grant review, 1999 - 1999
Joseph Stokes Institute MAPS/CHRC Grant Review, 1999 - 1999
Ad Hoc Reviewer for NIDDK - Program Project Review 8/10-8/12/1999, 1999 - 1999
March of Dimes, adjunct reviewer, 2002 - 2002
SSSY Study section, March 2003, November 2003, November 2004, 2002 - 2004
Ethel Brown Foerderer Medical Advisory Review Subcommittee at The Children's Hospital of Philadelphia, Joseph Stokes Research Center, 2003 - 2003
NIH Study Section (ad hoc)-Genetics of Health & Disease (GHD), 2004 - 2005
NIH Center for Scientific Review, 2005 - 2010
NIH Members conflict study section (BDCN, IRG) November 2005 (ad hoc), 2005 - 2005
Alagille Syndrome Alliance, 2006 - Present
NIDDK funded Center for Molecular Studies in Digestive & Liver Diseases, 2007 - 2014
Comitato Telethon Fondazione ONLUS, Via Nino Bixio, 30, 20129 Milan, Italy, 2008 - 2008
Institute for Diabetes, Obesity & Metabolism, and Diabetes Endocrinology Research Center. Pilot for Feasibility Study Grant Review., 2008 - 2008
American Society of Human Genetics (ASHG), 2012 - 2012
NHGRI CEGS study section, 2012 - 2012
Alagille Syndrome Alliance, 2012 - 2012
National Human Genome Research Institute (NHGRI), 2013 - 2013
American Society of Human Genetic (ASHG), 2013 - 2013
American Society of Human Genetics, 2016 - 2016
American Society of Human Genetics, 2016 - 2016
American Society of Human Genetics (ASHG), 2017 - 2019
American Society of Human Genetics (ASHG), 2017 - 2018
American Society of Human Genetics (ASHG), 2019 - 2022
American Society of Human Genetics (ASHG), 2020 - 2021
American Society of Human Genetics, 2024 - 2027
NIH Center for Scientific Review (CSR), 2024 - 2024
American College of Medical Genetics, 2024 - 2027

Web Links

Selected Publications

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