; 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)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
United States
Zip Code
Zamudio, Jesse R; Kelly, Timothy J; Sharp, Phillip A (2014) Argonaute-bound small RNAs from promoter-proximal RNA polymerase II. Cell 156:920-34
Xue, Wen; Dahlman, James E; Tammela, Tuomas et al. (2014) Small RNA combination therapy for lung cancer. Proc Natl Acad Sci U S A 111:E3553-61
Wu, Xuebing; Scott, David A; Kriz, Andrea J et al. (2014) Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat Biotechnol 32:670-6
Xue, Wen; Chen, Sidi; Yin, Hao et al. (2014) CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature 514:380-4
Dimitrova, Nadya; Zamudio, Jesse R; Jong, Robyn M et al. (2014) LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint. Mol Cell 54:777-90
Yin, Hao; Xue, Wen; Chen, Sidi et al. (2014) Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol 32:551-3
Maynard, M A; Ferretti, R; Hilgendorf, K I et al. (2014) Bmi1 is required for tumorigenesis in a mouse model of intestinal cancer. Oncogene 33:3742-7
Gurtan, Allan M; Ravi, Arvind; Rahl, Peter B et al. (2013) Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts. Genes Dev 27:941-54
Leung, Anthony K L; Sharp, Phillip A (2013) Quantifying Argonaute proteins in and out of GW/P-bodies: implications in microRNA activities. Adv Exp Med Biol 768:165-82
Wu, Xuebing; Sharp, Phillip A (2013) Divergent transcription: a driving force for new gene origination? Cell 155:990-6

Showing the most recent 10 out of 177 publications