The major goals ofthe Core B (Bioinformatics) are to provide the Program with the computational tools and expertise needed to process, analyze, integrate and interpret complex ChlP-Seq and gene expression profiling datasets obtained from normal and malignant T cell progenitors. To date, programmatic needs in these areas have been provided on an ad hoc basis. Creating this Core will provide the Program with dedicated longitudinal informatics and biostatistical support, which is important for the Program's overall success. The facility is headed by Dr. X. Shirley Liu, an experienced, highly productive computational biologist and biostatistician with a track record of innovation in computational analysis of cancer cell epigenetics and gene regulation. Its principle responsibilities will include analysis of ChlP-Seq data obtained from human and murine T-ALL cell lines, human and murine pnmary T-ALLs, and nonnal human and murine thymocyte subsets;analysis of gene expression profiles and/or RNASeq obtained from these cells; and integrative modeling ofthese ChlP-Seq and gene expression datasets.
The specific aims of Core B in the next project period are as follows:
Aim 1. To process, analyze, and integrate ChlP-Seq and gene expression datasets from normal and malignant T cell progenitors Aim 2. To characterize and quantify epigenetic changes associated with T cell differentiation or perturbation of transcription factors in T-ALL cells Aim 3. To advise Program Pis on study design and computational/technological advances Aim 4. To serve as a data repository and resource center for the program and the biomedical research community as a whole

Public Health Relevance

The Bioinformatics Core provides services that are needed forthe Program to meet its overall scientific goals, which are focused on understanding how Notch receptors are activated and turn on the expression of genes that drive the growth and survival of cancer cells. This shared resource provides sophisticated computational biology tools and expertise that allow Program to reach these goals in an expeditious, cost-effective fashion, and in doing contributes to elucidation of fundamental aspects of Notch signaling in cancer.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01CA119070-08
Application #
8701035
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
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Bernasconi-Elias, P; Hu, T; Jenkins, D et al. (2016) Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35:6077-6086
Chiang, Mark Y; Wang, Qing; Gormley, Anna C et al. (2016) High selective pressure for Notch1 mutations that induce Myc in T-cell acute lymphoblastic leukemia. Blood 128:2229-2240
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McMillan, Brian J; Tibbe, Christine; Jeon, Hyesung et al. (2016) Electrostatic Interactions between Elongated Monomers Drive Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein. Cell Rep 16:1211-7
Xu, Xiang; Choi, Sung Hee; Hu, Tiancen et al. (2015) Insights into Autoregulation of Notch3 from Structural and Functional Studies of Its Negative Regulatory Region. Structure 23:1227-35
McMillan, Brian J; Schnute, Björn; Ohlenhard, Nadja et al. (2015) A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb E3 ligases. Mol Cell 57:912-24
Wang, Hongfang; Zang, Chongzhi; Liu, X Shirley et al. (2015) The role of Notch receptors in transcriptional regulation. J Cell Physiol 230:982-8
Gordon, Wendy R; Zimmerman, Brandon; He, Li et al. (2015) Mechanical Allostery: Evidence for a Force Requirement in the Proteolytic Activation of Notch. Dev Cell 33:729-36
Wang, Hongfang; Zang, Chongzhi; Taing, Len et al. (2014) NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proc Natl Acad Sci U S A 111:705-10

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