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Center for Cancer Research
The unique strengths of the Center for Cancer Research (CCR) are the exceptional quality of its faculty and the ways in which the CCR's basic scientists collaborate with Mass General’s leading oncologists, surgeons, radiologists, pathologists, and other health care professionals to advance the frontiers of cancer medicine.
Welcome to the website for the Center for Cancer Research. This center serves as the engine for discovery. We have 41 independent laboratories with faculty drawn from all departments of Harvard Medical School. Our faculty study everything from Cancer cell genetics and epigenetics, metabolism and microenvironments, cell signaling and DNA damage, with studies of cultured cells, all the way to patient derived samples and specimens. I encourage you to visit our website, view all the investigators summaries, look through our news and events, and our current publication highlights.
[Archive of Past Publications]
SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b In this Featured Article in the June 2nd issue of Cell, a group of authors led by Sita Kugel from Raul Mostostavsky’s laboratory, identifies SIRT6 as an important new therapeutic target in pancreatic ductal adenocarcinoma. The paper describes how the histone deacetylase SIRT6 acts as a regulator of a Lin28b/let-7 pathway critical for the growth of these tumors. Click HERE and HERE for more information.
Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. In this April 2016 paper in Nature Genetics, Jaegil Kim, Kent Mouw (not pictured), and Paz Polak from Gad Getz's laboratory identified a unique mutational signature associated with somatic alterations in the ERCC2 core nucleotide-excision repair gene in urothelial tumors. The activity of this signature was also associated with smoking independent of ERCC2 mutation status, providing genomic evidence of tobacco-related mutagenesis in urothelial cancer. Click here for more information.
A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence. In this March 2016 paper in Molecular Cell, Syed Bukhari and co-authors, Samuel Truesdell, Sooncheol Lee and Swapna Kollu from Shobha Vasudevan’s laboratory, reveal that microRNAs mediate a novel non-canonical translation initiation mechanism responsible for the translational upregulation of specific deadenylated mRNAs in quiescent human leukemic cells and immature frog oocytes. Because quiescence plays critical roles in early development and contributes to clinical resistance in cancers, the discovery of this mechanism has important implications for understanding developmental processes and tumor resistance.
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. In this January 2016 paper in Nature, Benjamin Kleinstiver, Vikram Pattanayak, Michelle Prew and others from Keith Joung’s laboratory describe a modified high-fidelity nuclease that allows CRISPR-Cas9 genome editing without detectable off-target effects. The ability to greatly reduce off-target effects will provide an alternative higher-fidelity Cas9 for genome editing experiments, and brings closer eventual therapeutic applications of the technology.
Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. In their January 2016 paper in Cell, Nicholas Haradhvala, Paz Polak, Michael Lawrence and others from Gad Getz’s lab report that mutational asymmetries with respect to replication (leading vs. lagging strand) and transcription (transcribed vs. non-transcribed strand) are widespread in cancer. They also show that APOBEC generates mutations on the lagging strand and that an unknown process damages the non-transcribed strand in liver cancer.
Insulator dysfunction and oncogene activation in IDH mutant gliomas. In this January 2016 paper in Nature, William Flavahan and Yotam Drier from Brad Bernstein’s lab, with other MGH and Broad Institute colleagues, report that DNA hypermethylation of IDH mutant gliomas results in insulator dysfunction and inappropriate expression of PDGFRA, a potent glioma oncogene. The authors conclude that IDH mutations promote gliomagenesis by disrupting chromosomal topology and inducing oncogene expression.
Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. In this October 2015 paper in Nature Medicine, Alexandre Wagschal from Anders Näär’s lab, and co-authors from MGH and elsewhere, report that 4 microRNAs located near SNPs associated with altered blood lipid levels regulate key proteins involved in cholesterol-lipoprotein trafficking. Functional studies support that altered microRNA expression contributes to abnormal blood lipid levels and may predispose individuals to cardiometabolic disorders.
Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase. In this September 2015 paper in Molecular Cell, Rémi Buisson and Jessica Boisvert from the labs of Cyril Benes and Lee Zou report that cells in early S-phase undergo mitotic catastrophe when subjected to ATR inhibition (ATRi). This reflects a key role for ATR in coordinating RRM2 accumulation and origin firing. Importantly, the level of ATRi-induced ssDNA can serve as a biomarker predicting the ATRi sensitivity of cancer cells.
Transcriptional control of autophagy–lysosome function drives pancreatic cancer metabolism. In this July issue of Nature, Rushika Perera from Nabeel Bardeesy’s laboratory and colleagues identify a transcriptional program regulating nutrient scavenging pathways (autophagy and the lysosome) in pancreatic cancer. They show that increased function of these pathways allows efficient recycling of proteins and other cargo, which sustains intracellular amino acid levels and supports tumor growth.
Hypoxia drives transient site-specific copy gain and drug-resistant gene expression. In this May 2015 paper in Genes & Development, co-first authors Joshua Black and Elnaz Atabaksh from Johnathan Whetstine’s lab report that hypoxia drives sites-specific gene copy number gains in normal as well as in tumor cells. This evolutionary conserved response depends on the KDM4A histone demethylase and is blocked by inhibiting this enzyme. CSK1B, implicated in chemotherapy resistance, is among the genes amplified in response to hypoxia.
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