 | Cornering Cancer
Koch Institute researchers are teaming up to put p53-mutated cancers in a corner by targeting multiple genes at once to create a new approach called “augmented synthetic lethality.” Mutations in the p53 tumor suppressor gene (present in most cancers) enable tumor cells to develop resistance to widely-used platinum-based chemotherapies. Building on previous work in the Yaffe Lab that identified MK2 as a synthetic lethal partner to p53, the group has now been able to further enhance the tumor-shrinking effects of platinum-based anti-cancer drugs by adding a new target, the gene XPA. In the study, appearing in Nature Communications, Yaffe lab researchers used nanoplexes developed in the Hammond Lab to deliver MK2- and XPA-blocking siRNAs to tumors in mouse models of non-small cell lung cancer that were originally developed in the Jacks and Hemann Labs.
This work was supported in part by a Mazumdar-Shaw International Oncology Fellowship, a postdoctoral fellowship from the S. Leslie Misrock (1949) Frontier Research Fund for Cancer Nanotechnology and by the Charles and Marjorie Holloway Foundation, the Ovarian Cancer Research Foundation, and the Breast Cancer Alliance. |
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RUNX, RUNX as Fast as You Can
The Jacks Lab is analyzing lung tumors’ evolution by measuring structural changes to chromatin—the mix of proteins, DNA, and RNA that makes up cells’ chromosomes that can alter gene expression. In work published by Cancer Cell, researchers showed that these epigenomic modifications can characterize the progression of cancer cells from early stage to later, more aggressive stages. They also identified a transcription factor—a molecule known as RUNX2—that influences metastasis in these evolving cells. Looking at both mouse and human tumors, the team found that elevated levels of RUNX2 are associated with increased tumor cell aggressiveness, suggesting that it could be used as a biomarker to predict patient outcomes. |
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Michelson Prize for Michael Birnbaum
Michael Birnbaum received the Michelson Prize for Human Immunology and Vaccine Research 2020 to identify target antigens for HIV vaccine development. His team’s novel methodology for studying immune cells’ antigen recognition repertoire has multiple applications for other diseases, including cancer and COVID-19, and exemplifies the type of promising early career research supported by the prize. |
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Fewer Needles, More STING
A programmable microparticle developed by Langer Lab researchers could make STING-based cancer therapies easier for patients to complete. In a study appearing in Science Translational Medicine and supported in part by a Ludwig Postdoctoral Fellowship and a Misrock Postdoctoral Fellowship, researchers found the microparticles to be as effective against tumors as multiple injections in mouse models of melanoma and breast cancer, with a reduced chance of metastasis. |
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2020 Visions: A Virtual Celebration Join us on September 22 & 24 for a two-part virtual celebration of 2020 Visions, the tenth annual Image Awards exhibition now on display in the Koch Institute Public Galleries. Celebrating biological beauty and transformative technologies, this year’s displays embrace a variety of visualization techniques to examine the inner workings of microscopic communities and human health. Over the course of two “lunch & learn” webinars, image creators will share the science and stories behind their award-winning visuals. |
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Shedding Metabolite on Pancreatic Cancer
Vander Heiden Lab researchers are using a novel nutrient-labeling approach to understand metabolic differences between cell types. A new study published in eLife examines enzyme activity of tumor cells and fibroblasts in organoid cell cultures and mouse models of pancreatic ductal adenocarcinoma, and suggests potential pathways for curtailing tumor growth.
This work was funded in part by the MIT Center for Precision Cancer Medicine. Proof of concept investigations were conducted with support from the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund. |
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Nanoparticles on Trachea to Greatness
Bhatia Lab researchers are breathing new life into their signature protease activity nanosensors. Chemical modifications to synthetic biomarkers (previously used to develop urinary diagnostics for pneumonia and cancer) allow the nanoparticles to release a peptide-based “breath signal” in the presence of respiratory disease. The re-engineered system, described in Nature Nanotechnology, can be used for both diagnosis and monitoring of disease progression or treatment. The researchers are modeling future iterations of the technology on inhalers and breathalyzer tests, and hope to use it to detect specific pathogens such as the SARS-CoV-2 virus |
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Standing Up to Pancreatic Cancer
Congratulations to Will Freed-Pastor and fellow Lustgarten Laboratory for Pancreatic Cancer Research at MIT researchers on the receipt of a Phillip A. Sharp Innovation in Collaboration Award from Stand Up To Cancer. The Jacks Lab/Dana Farber Cancer Institute team, in conjunction with researchers at Fred Hutchinson Cancer Research Center, will use tumor organoids and engineered T cells to develop novel interventions against pancreatic cancer. |
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Wittrup Lab Sticks It to Tumors
The Wittrup Lab's “Velcro vaccine” is the not-so-secret weapon behind Cullinan Oncology’s newly launched subsidiary, Cullinan Amber. The company aims to enhance cytokine-based immunotherapy using the lab’s collagen-binding technology, which confines these powerful yet toxic treatments to the tumor microenvironment. |
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Campus Shuts Down, Nelson Steps Up
Toni-Ann Nelson, an undergraduate researcher from Alcorn State University, has been working with MSRP-Bio and Jacks Lab graduate student Amanda Cruz to understand the genetic underpinnings of non-small cell lung cancer...in unexpectedly quantitative ways. Thanks to the MIT campus closure, Nelson has developed a new computational skillset that will help transform her lifelong passion for cancer research into new cancer biology pathways. |
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On the Node Again
Elicio Therapeutics is developing the Irvine Lab’s lymph node targeting vaccine technology to fight COVID-19. With promising preclinical evidence of increased T cell and antibody response against coronavirus proteins, the company hopes to accelerate clinical translation using insight gained from their already-completed manufacturing and toxicology studies in KRAS-driven cancers. |
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Two More Against Tumors
Two studies from the Yaffe Lab showcase the versatility of interdisciplinary approaches to accelerate deep understanding of biological phenomena.
In the first paper, appearing in Nature Communications, researchers show that Brd4 function is necessary to block collisions on genomic DNA between sites of RNA transcription and DNA replication. Read more »
A second paper in Cell Reports describes a computer program called Transite, which allows researchers to find key RNA-binding proteins from any gene expression dataset. In the paper, researchers identified a new RNA-binding protein, hnRNPC, as a modulator of chemotherapy resistance. Read more » |
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