Regulation of Foxp3 Function
The goal of the project is to use ChiP-seq technology to understand how Foxp3 and Ikaros regulate T cell differentiation.
Funded By:National Institute of Allergy and Infectious Diseases
5 R01 AI070807 (Wells )
Bioinformatics Core members involved: Juan Carlos Perin

Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
The goal of this project is to identify clinically relevant modifiers of the severity of hepatic disease in patients with Alagille Syndrome (AGS).
Funded By: National Institute of Diabetes and Digestive and Kidney Diseases
1R01DK081702-01A1 (Spinner)
Bioinformatics Core members involved:Xiaowu Gai, Hongbo Xie

Islet Dysregulation in Infants with Congenital Hyperinsulinism
Congenital hyperinsulinism (HI) is the most frequent cause of persistent hypoglycemia in infants and children. Although 6 such loci have been found, many children with HI have no identifiable mutation of these genes. Our hypothesis is that hyperinsulinism in these groups of children involves both novel molecular defects of known loci, as well as, previously unrecognized new genetic loci. The long-term goal of the project is to identify genotype-phenotype correlations in these disorders to guide diagnosis and treatment and to uncover new forms of congenital hyperinsulinism.
Funded By: National Institute of Diabetes and Digestive and Kidney Diseases
2R37DK056268-1109 (Stanley)
Bioinformatics Core members involved:Juan Carlos Perin

Genome Copy Number Variation Analytics
The major goals of this project are to develop methods for high-throughput analysis of genome surveillance data for identifying CNV, to create tools for assessing CNVs in a wider biomedical context, and to develop a process for using the analytical results for improved clinical diagnostics and delivery to the EHR.
Funded By: Pennsylvania Department of Health (White)
Bioinformatics Core members involved: Peter White (PI), Xiaowu Gai, Juan Perin, and Monica D’Arcy

NIPBL, Cohesin and Related Structural Birth Defects
The major goals of this project are to sytematically study NIPBL, its interacting proteins and downstream target genes and to characterize the effects this gene and pathway has on human structural birth defects. A three-pronged approach to studying this gene and pathway in humans, mouse, zebrafish, and Drosophila, will synergistically characterize the function, interactions and role of NIPBL and its downstream targets in causing syndromic and isolated human structural birth defects.
Funded By: Eunice Kennedy Shrinver National Institute of Child Health & Human Development
P01 (Krantz)
Click here to see the CRISP entry
Bioinformatics Core members involved: Xiaowu Gai and Juan Perin

Mental Retardation and Development Disabilities Research
The proposed Mental Retardation and Developmental Disabilities Research Center (MRDDRC) was established in 1990 and renewed in 1995 and 1999. It represents the collaboration of the Children's Hospital of Philadelphia and the University of Pennsylvania (Penn). In this renewal application, funds are requested to support five core facilities and New Program Development projects, one of which is the Bioinformatics Core at The Children’s Hospital of Philadelphia Research Insitute.
Funded By: Eunice Kennedy Shrinver National Institute of Child Health & Human Development
P30 (Yudkoff)
Click here to see the CRISP entry
Bioinformatics Core members involved: Xiaowu Gai

Copy Number Alterations in Genomic Disorders
The goal of this proposal is to identify previously undetectable, disease-causing copy number alterationss in patients with multiple congenital anomalies (MCA). The identification of genomic regions altered in MCA patients will allow a better understanding of the mechanisms underlying this group of disorders. We can then begin to assess the role of gene(s) in these regions that may be critical to early human developmental pathways. The identification of genomic regions that are deleted or duplicated in patients with birth defects will allow the identification of genes that are important in normal development.
Funded By: National Institute of General Medical Sciences
R01 (Shaikh)
Click here to see the CRISP entry
Bioinformatics Core members involved: Xiaowu Gai and Hongbo Xie

Translational Genomic Study of Mitochondrial Complex I Dysfunction in C. elegans
This project will clarify contributions of structural subunits of complex I to integrated mitochondrial function in C. elegans. Specific aims for this proposal are to: 1) Determine which of the evolutionary conserved, nuclear-encoded subunits of complex I are integral to mitochondrial function in C. elegans, and 2) Identify a representative gene expression-based pattern within biologically relevant pathways that is indicative of MRC dysfunction.
Funded By: National Institute of Diabetes and Digestive and Kidney Diseases
K08 (Falk)
Click here to see the CRISP entry
Bioinformatics Core members involved: Zhe Zhang

Regulation of Erythropoiesis by microRNA's
We will study the functions of miRNA144/451 by ablating the gene in mice and determining the consequences on blood formation. We will use these mice, along with methods to manipulate miRNA144/451 expression in cultured cells, to better define the genetic pathways through which this important microRNA gene exerts its effects. If successful, our studies will illustrate new principles in the basic biology of red blood cell formation and function. In addition, defining the actions of miRNA144/451 could illustrate molecular pathways that could be manipulated pharmacologically for the treatment of various anaemias.
Funded By: Roche Foundation for Anemia Research (Weiss)
Click here to see this entry
Bioinformatics Core members involved: Zhe Zhang