What's the Big Idea ?; Heads Together for Brain Cancer; Ritu Raman named L’Oréal USA Fellow

The Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center (DF/HCC), took home top honors at the inaugural Xconomy Awards, winning the coveted "Big Idea" award for its simple-yet-revolutionary strategy of bringing together MIT researchers with physician-scientists from DF/HCC to "bridge the gap" between bench and bedside to accelerate novel research approaches and technologies into the clinic. The award marks a significant milestone in the public recognition of the Bridge Project, which was launched in 2012 by founding donor Arthur Gelb, KI Director Tyler Jacks, and DF/HCC Deputy Director David Livingston, but the initiative itself shows no signs of resting on its laurels. Thus far, the Bridge Project has advanced 37 joint projects, with a new funding cycle on the horizon, and boasts 11 invention disclosures, 4 companies, and, as of press time, 7 projects in or close to the clinic. Read about the award here and stay tuned for our next issue as we highlight KI member Sangeeta Bhatia's "Innovation at the Intersection" Xconomy Award win!

Researchers from the Hemann, Lees, and Sharp laboratories joined forces in the fight against glioblastoma. Using a novel screen, the collaborative team identified PRMT5 as a protein involved in the tumors’ growth, and found that PRMT5 uses a special type of gene splicing to promote this growth.The researchers showed that inhibiting PRMT5 halted cancer cell growth in mice, and also identified a biomarker that could be used to predict which patients would benefit from treatment with existing PRMT5 inhibitors, at least one of which is currently in clinical trials for cancer. Their findings, described in Cancer Cell, help explain PRMT5’s poorly understood role in cancer and offer opportunities to improve current therapies and develop new ones. The team hopes to develop nanoparticles to help PRMT5 inhibitors cross the blood-brain barrier, and is also looking at PRMT5’s role in other tumor types.

This work was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund. Read more and watch recent Lees Lab PhD recipient Monica Stanciu present this research as part of the Koch Institute’s SOLUTIONS with/in/sight: Fast-Moving Frontiers program.

In recognition of her contributions to the advancement of STEM fields and for her support of women and girls in science, Langer Lab postdoc Ritu Raman has been awarded the L’Oréal USA For Women in Science Fellowship. The L’Oréal USA For Women in Science Fellowship recognizes female scientists at a critical early stage in their careers with grants to advance their postdoctoral research. Raman, who was also recently named one of six Convergence Scholars by the Marble Center for Cancer Nanomedicine, plans to use her L’Oréal USA award funds to support her research developing bio-hybrid materials for long-term sensing and drug delivery, and her collaborations with scientists, engineers, and clinicians across the country. A staunch advocate for STEM education and outreach, Ritu hopes to one day open her own lab to teach others how to build with adaptive materials, and develop curricula that explore the ethics and mechanics of building with biology. Read more.

Jacks Lab researchers are exploring a new way to treat aggressive lung cancer driven by "undruggable" mutations in the KRAS gene. A second gene, KEAP1, is mutated alongside KRAS in about 17% of lung adenocarcinoma cases. The team discovered that in those cases, the cancer cells rely on the use of glutamine, an amino acid essential for metabolic processes, as an energy source. Inhibiting glutaminase, an enzyme critical for glutamine metabolism, would thus offer a new method to treat tumors that harbor KRAS and KEAP1 mutations. Indeed, the researchers found that blocking glutaminase, using the small molecule inhibitor CB-839, reduced tumor growth in culture and in mice. These findings, described in Nature Medicine, offer a potential strategy for identifying the lung cancer patients that would likely respond well to CB-839 in the clinic. CB-839 is currently in Phase 1 clinical trials for KRAS-mutant lung cancer. Read more.

Congratulations to KI member and Daniel K. Ludwig Professor for Cancer Research, Richard Hynes, for being named the recipient of the 2017 David Rall Medal from the National Academy of Medicine (NAM). Hynes was chosen for his leadership as the co-chair of the NAM/NAS Report Committee on Human Genome Editing. To honor his recent award, Hynes sat down with NAM to discuss his research, his inspiration for getting involved in policy work, and his thoughts on how to better engage public interest in science and medicine — read here.

Researchers in the laboratory of KI member Timothy Lu have been working to develop targeted immunotherapies to attack cancer cells. Through the use of customized DNA/RNA sequences, the team has designed a synthetic gene circuit that is activated by transcriptional signals expressed by tumor cells, triggering a combinatorial immune response. Their bioengineered "switch" requires two cancer-specific signals to be present before it turns on, making it more accurate than current therapies, and can also be customized to recognize and target different cancer types. Read more.

Salil Garg (Sharp Lab), Jiang He (Bhatia Lab), and Michael Mitchell (Langer Lab) were all named 2017 STAT Wunderkinds for their work "blazing new trails as they attempt to answer some of the biggest questions in medicine." Langer Lab alumni Carl Schoellhammer, CEO of Suonobio, and Armon Sharei, CEO of SQZ Biotech, were both among Business Insider's 30 biotech leaders under 40 list. Sharei also received the "Young Innovator" award at this year's Xconomy Awards!

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US and despite some advances in treatment approaches, the long-term survival of patients remains extremely poor. Mutations in KRAS are a hallmark of this cancer type, occurring in >90% of cases, making this gene an attractive therapeutic target. New research from the laboratory of Tyler Jacks, a David H. Koch Professor of Biology and director of the Koch Institute, investigated whether PDAC cells are dependent on KRAS for their growth. Using CRISPR/ Cas9 to completely delete KRAS, the researchers determined that a subset of PDAC cells are still able to survive. However, the cells that do survive are sensitive to inhibitors of the PI3K pathway, suggesting that the simultaneous inhibition of KRAS and PI3K would be a viable combinatorial therapeutic strategy.

There's na-no ifs, ands, or buts about it — nanotechnology is clearly a driving force in the prolific career of Robert Langer, member of the KI and the Marble Center for Cancer Nanomedicine. For his work on the design and development of novel carriers for improved small molecule drug delivery, Langer was awarded the 2017 Kabiller Prize in Nanoscience and Nanomedicine from Northwestern University’s International Institute for Nanotechnology. The Kabiller Prize honors outstanding achievement in the field of nanotechnology and its application to medicine and biology. Read more about Langer's latest honor, view the accompanying video, or listen to him on the NorthwesternU podcast.

This fall marks the 13th year of the Margaret A. Cunningham Immune Mechanisms of Cancer Fellowships, supported by the John D. Proctor Foundation and the Rhode Island Foundation’s Margaret A. Ames and Robert S. Ames Donor Advised Fund. On October 10, John Proctor, MIT Sloan alumnus and trustee of the John D. Proctor Foundation, was on hand at the Koch Institute to meet and talk with current and former Cunningham Fellows about their research projects. The fellowship program was created in memory of Proctor’s wife, Margaret, in 2004, and supports graduate students, medical students and post-doctoral fellows engaged in novel, independent research projects in cancer immunology. Cunningham Fellowship recipients have gone on to positions in academia, industry, and medicine.

Researchers, physicians, and patients alike received encouraging news this fall from MIT startup Alnylam, a pioneer in the field of RNA interference (RNAi) therapy. The pharmaceutical company, founded in 2002 by a team of scientists, including KI faculty member and MIT Institute Professor Phillip Sharp, announced the first-ever positive Phase 3 results for an RNAi therapeutic. This news opens up a new class of medicines for gene therapy in multiple areas as RNAi is disease-agnostic. Sharp Lab alumnus Andrew Fire received the Nobel Prize in 2006, along with Craig Mello, for its discovery; many current KI researchers are working to advance RNAi and related technologies.

Join the Koch Institute as we host Upstage Lung Cancer for “From Bench to Broadway” on Thursday, December 7. This evening of live performances of Broadway hits will benefit groundbreaking research for early detection and diagnosis of lung cancer through the Koch Institute Frontier Research Program. The show begins at 7:30 PM, following a silent auction at 6:00 PM. Learn more and buy tickets here.