The molecular genetics component of Program 1 will build on the progress of this aspect of the Program over the past five years. For example, super-enhancers particularly those that appear to control many activated oncogenes, offer possible new approaches to the diagnosis and treatment of cancer. Large non-coding RNAs control gene expression is a focus of research in this Program, and these are likely to control important aspects of tumor genesis. CRISPR technology is a very powerful tool for research on cancer, allowing rapid mutation of many genes in parallel and physically targeting transcription-modulating signals to specific sites on the genome. Small non-coding RNAs such as microRNAs are tightly integrated into networks that control the malignant state, but this has neither been fully illuminated nor set into the regulatory networks of genes important in cancer. These topics and others are developed in the research sections of 1) roles of transcriptional super-enhancers in control of cell identity and cancer, 2) large noncoding RNAs and cancer, 3) probing cancer genomes with CRISPR technology, 4) small non-coding RNAs and cancer, 5) cancer genome and transcriptome analysis, and 6) synthetic biology and cancer. The immunology component of Program 1 features a deep integration of engineering approaches with immunological science to advance our understanding of the interaction of cancer cells with the immune system and develop new forms of immunotherapy. The immunoengineering perspective is a particular strength of the Program and is an instantiation of the broader phenomenon of convergence between engineering and the life sciences in the Koch Institute. Immunology, in particular, is a field that is amenable to both analytical engineering and design engineering. Decoding communications between cells in the immune system using principles of chemical engineering and synthesis and engineering synthetic vaccines using cues from natural immunity are strengths of the Program. These topics and others are discussed in sections 1) therapeutic cancer vaccine development, 2) synergistic antibody/IL-2 immunotherapy, 3) mouse/human models of follicular B cell lymphoma, 4) whole exome sequencing of CTCs as a window into metastatic cancer. Program 1 has 16 Members from 5 Academic Departments at the School of Science or School of Engineering at MIT. The Membership has a cancer-related funding base of $ 24,934,945 TDC. From 4/1/2009, the Membership of Program 1 published 508 cancer-related articles. Of those, 107, or 21%, have involved multiple members; 45, or 8.9%, intra-programmatic, and, 62 or 12.2%, inter-programmatic; 4 are both intra- and interprogrammatic.

Public Health Relevance

Overall Component: Project Narrative The Koch Institute for Integrative Cancer Research at MIT is a highly inter-disciplinary Cancer Center that brings together the great strengths at MIT in cancer science and cancer-oriented engineering to address long- standing problems in the diagnosis and treatment of cancer. The Koch Institute is focused on basic discovery and technology development; however, advancing projects toward the clinic and to the benefit of patients as rapidly as possible is a high priority. This occurs through extensive interactions with clinical centers as well as industry partners.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA014051-46
Application #
9282607
Study Section
Subcommittee A - Cancer Centers (NCI-A)
Program Officer
Shafik, Hasnaa
Project Start
1997-06-17
Project End
2020-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
46
Fiscal Year
2017
Total Cost
$3,572,644
Indirect Cost
$1,171,589
Name
Massachusetts Institute of Technology
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Weidberg, Hilla; Amon, Angelika (2018) MitoCPR-A surveillance pathway that protects mitochondria in response to protein import stress. Science 360:
Chiu, Anthony C; Suzuki, Hiroshi I; Wu, Xuebing et al. (2018) Transcriptional Pause Sites Delineate Stable Nucleosome-Associated Premature Polyadenylation Suppressed by U1 snRNP. Mol Cell 69:648-663.e7
Nagarajan, Maxwell B; Tentori, Augusto M; Zhang, Wen Cai et al. (2018) Nonfouling, Encoded Hydrogel Microparticles for Multiplex MicroRNA Profiling Directly from Formalin-Fixed, Paraffin-Embedded Tissue. Anal Chem 90:10279-10285
Mead, Benjamin E; Ordovas-Montanes, Jose; Braun, Alexandra P et al. (2018) Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol 16:62
Chen, Tiffany F; Li, Kevin K; Zhu, Eric F et al. (2018) Artificial Anti-Tumor Opsonizing Proteins with Fibronectin Scaffolds Engineered for Specificity to Each of the Murine Fc?R Types. J Mol Biol 430:1786-1798
Dayton, Talya L; Gocheva, Vasilena; Miller, Kathryn M et al. (2018) Isoform-specific deletion of PKM2 constrains tumor initiation in a mouse model of soft tissue sarcoma. Cancer Metab 6:6
Koblan, Luke W; Doman, Jordan L; Wilson, Christopher et al. (2018) Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol 36:843-846
Suarez-Lopez, Lucia; Sriram, Ganapathy; Kong, Yi Wen et al. (2018) MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis. Proc Natl Acad Sci U S A 115:E4236-E4244
Guner-Ataman, Burcu; González-Rosa, Juan Manuel; Shah, Harsh N et al. (2018) Failed Progenitor Specification Underlies the Cardiopharyngeal Phenotypes in a Zebrafish Model of 22q11.2 Deletion Syndrome. Cell Rep 24:1342-1354.e5
Phizicky, David V; Berchowitz, Luke E; Bell, Stephen P (2018) Multiple kinases inhibit origin licensing and helicase activation to ensure reductive cell division during meiosis. Elife 7:

Showing the most recent 10 out of 904 publications