; The Core supports two activities that are important to all of the projects. The first of these is the engagement of Dr. Arjun Bhutkar as a half-time Bioinformatics Specialist (Bio-sp) for analysis of results from microarrays and deep sequencing of RNA preparation. Dr. Bhutkar has significant expertise and experience in the analysis of large databases from microarray formats and from deep RNA sequencing formats (see CV). He has collaborated with students and fellows in all three projects. As a member of this Program, Dr. Bhutkar will also help design and analyze experiments where crosslinking is used to characterize protein-DNA complexes, Protein-RNA complexes, and RNA-RNA complexes. He will also help adapt deep sequencing to define the transcriptome of cells. Over time this will displace the use of microarray in characterization of cancer cells. Because computation needs to be designed into the experimental protocol at the onset, it is important to have a committed and knowledgeable Bio-sp available to the three projects.
Core Specific Aim 1. Addition of Dr. Bhutkar as a Bioinformatics Specialist will facilitate for all three projects (a) the analysis of microarray results in comparison of tumor cells, (b) processing of large data sets from high-throughput sequencing of DNA sequences bound to proteins, and (c) complexes of coding and non-coding RNAs bound to proteins and RNAs. Inclusion of Dr. Bhutkar's expertise in the design of experiments as well as analysis will reduce the cost of the use of expensive and limited sequencing devices such as illumina Genome Analyzer and produce more valid results. The second activity of the Core that brings three projects together and is cost-effective is the sharing of common equipment, services, and materials. The use of this pool of equipment requires the interactions of investigators on a daily basis and is effective because all three labs occupy adjacent space on the same floor. All of the equipment supported by the Core is in shared space, 3,200 sq. ft. These Core funds are supervised by an assistant in the group and their purchase and repair are responsive to the needs of the three projects.
Core Specific Aim 2. To cover the expenses of some shared equipment, services and materials that are necessary for the three projects and facilitate the interactions of investigators in the group in a cost-effective manner.

Public Health Relevance

Advancement of technology and bioinformatics in analysis of populations of RNAs such as the transcriptome, RNAs bound to proteins and other RNAs and DNA-protein complexes will produce new opportunities to diagnosis and treat cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-O)
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Massachusetts Institute of Technology
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Mori, Munemasa; Hazan, Renin; Danielian, Paul S et al. (2017) Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis. Nat Commun 8:15857
Sasi, Nanda Kumar; Bhutkar, Arjun; Lanning, Nathan J et al. (2017) DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways. Neoplasia 19:439-450
Hnisz, Denes; Shrinivas, Krishna; Young, Richard A et al. (2017) A Phase Separation Model for Transcriptional Control. Cell 169:13-23
JnBaptiste, Courtney K; Gurtan, Allan M; Thai, Kevin K et al. (2017) Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1-3 family. Genes Dev 31:674-687
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Dimitrova, Nadya; Gocheva, Vasilena; Bhutkar, Arjun et al. (2016) Stromal Expression of miR-143/145 Promotes Neoangiogenesis in Lung Cancer Development. Cancer Discov 6:188-201
Garg, Salil; Sharp, Phillip A (2016) GENE EXPRESSION. Single-cell variability guided by microRNAs. Science 352:1390-1
Zhang, Xiaochang; Chen, Ming Hui; Wu, Xuebing et al. (2016) Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. Cell 166:1147-1162.e15
Danielian, Paul S; Hess, Rex A; Lees, Jacqueline A (2016) E2f4 and E2f5 are essential for the development of the male reproductive system. Cell Cycle 15:250-60
Ferretti, Roberta; Bhutkar, Arjun; McNamara, Molly C et al. (2016) BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance. Genes Dev 30:18-33

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