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Remembering David Baltimore

MIT Koch Institute

With sadness, the Koch Institute marks the passing of Professor David Baltimore. A founding faculty member and formative influence behind the MIT Center for Cancer Research, he was not only a ground-breaking researcher but also a compelling and thoughtful voice for science. 

His discovery of reverse transcriptase changed the prevailing scientific dogma, earned him a 1975 Nobel Prize, and directly enables work in life sciences and biomedical laboratories everywhere. His decades-long advocacy work impacted national policy debates on topics such as recombinant DNA research, the AIDS epidemic, and genome editing.

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SeqWell S3: Better Than the Original

MIT News

Shalek and Love Lab researchers have increased the resolution on their signature high-throughput single-cell RNA-sequencing platform using a simple molecular biology trick known as "second-strand synthesis." The new and improved Seq-Well S3, described in Immunity, provides a five- and tenfold increase in identification of genes and RNA transcripts, respectively, and was applied to characterize various inflammatory skin conditions. The team is also using the technology to profile cancer cells, supported in part by the Bridge Project.

Breaking Up Isn't Hard to Do

Nature Communications

Cell division may look like hard work, but a team led by the Manalis Lab and including the Vander Heiden and Yaffe Labs found that mitosis may take much less energy than expected. In a study appearing in Nature Communications, researchers measured the membrane potential of mitochondria (the powerhouses of the cell) at single-cell resolution and then, using an “electrical circuit” mathematical model, estimated that mitochondria produce ATP (the cell’s primary fuel) about half as quickly during mitosis than outside mitosis.

This study was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the MIT Center for Precision Cancer Medicine, the Lustgarten Foundation, and the Ludwig Center at MIT.

NIH Honors Transformative Potential

MIT News

Congratulations to Michael Birnbaum on receipt of a National Institutes of Health New Innovators Award for his work using peptide-MHC lentivirus display to identify repertoire-scale T cell antigens. Administered through the High Risk, High Reward program, the award celebrates highly innovative and unusually impactful research by extraordinarily creative early career scientists. Birnbaum, who joined the Koch Institute faculty in 2016, uses protein engineering, structural biology, and bioinformatics to understand and manipulate immune-cell recognition and signaling.

Rising Stars

Endpoints News

Endpoints named Kronos Bio as one of 11 most promising startups in biotech. Built on high-throughput screening techniques developed by MIT Center for Precision Cancer Medicine member Angela Koehler, the company takes aim at “undruggable” cancer targets. Skyhawk, which draws on the research and expertise of several KI members, also made the list.

Advancing AI in Medicine

MIT News

KI member Regina Barzilay is the first-ever winner of the Association for the Advancement of Artificial Intelligence’s Squirrel AI Award for Artificial Intelligence for the Benefit of Humanity, a new $1 million prize to honor individuals whose work in the field has had a transformative impact on society. Barzilay is being recognized for her work building machine learning models to develop antibiotics and other drugs, and to detect and diagnose breast cancer at early stages. In 2019 she spoke at the Koch Institute’s with/in/sight lecture series about her collaboration with MGH’s Constance Lehmann to improve mammography through artificial intelligence and co-chaired the Koch Institute's annual summer symposium, on the integration of machine learning and cancer research. In addition to her own laboratory research, she is also working to make her diagnostic tools available for underprivileged populations around the world.

Cornering Cancer

Nature Communications

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.

Campus Shuts Down, Nelson Steps Up

MIT Biology

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.

Rapid Transite Accelerates Computational Analysis

Cell Reports

Members of the Yaffe group have been developing computational methods to examine RNA-binding proteins as a class of molecules that might broadly be involved in how tumors respond to chemotherapy. In a Cell Reports paper, the researchers describe a computer program they developed called Transite, which systematically infers which RNA-binding proteins are influencing gene expression through changes in RNA stability and degradation. Transite is broadly available at Transite and has already been used to perform hundreds of analyses.

This work was supported in part by the MIT Center for Precision Cancer Medicine and the Charles and Marjorie Holloway Foundation.

On the Node Again

Elicio Therapeutics

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.

RUNX RUNX As Fast As You Can

MIT News

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.