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Golden Anniversary for a Gold Medal

It’s Nobel season and this year commemorates the 50th anniversary of the prize being awarded to late MIT microbiologist Salvador E. Luria. Luria was recognized, along with two colleagues, for discoveries on the replication and genetics of viruses called bacteriophages; however, he is best known at MIT for a distinction garnered later in his career. As the founder and first director of the MIT Center for Cancer Research, he laid the foundation for MIT’s notable achievements in molecular and cellular oncology, which continue at the Koch Institute today. Learn more about Luria’s role in establishing MIT as a cancer research powerhouse, and new efforts to recognize his influence via the Koch Institute’s primary gathering spot, the auditorium.


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Big Questions in Cancer Biology

Since Luria’s day we have learned a great deal about cancer biology, but there are still fundamental aspects we don’t understand. Such topics are the subject of two recent reviews, papers we don’t often cover but are worth an exception today. First, for our many friends and readers who ask about diet and cancer, Koch Institute associate director Matthew Vander Heiden lays out a framework for thinking about and studying the relationship between the altered metabolism of cancer cells and the diet that we, as individual organisms, eat (hint, it’s not a 1:1 relationship). A second review, from Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, looks at the role aneuploidy, or incorrect chromosome number, plays in the development and treatment of cancer, where it is a feature of more than 90% of solid tumors. Her take? Context is key. 
 

Holding Court

On October 4, MIT's North Court was renamed in honor of Susan Hockfield, MIT’s 16th —and first female and first life scientist—president. Festivities included a reception and dedication ceremony with music and remarks given by Robert Millard ’73, chairman of the MIT Corporation, James Champy ’63 SM ’65, lifetime member emeritus of the MIT Corporation, and Paula Hammond ’84 PhD ’93, the David H. Koch (1962) Professor of Engineering and head of the Department of Chemical Engineering. Among the many achievements noted was the establishment of the Koch Institute. Hockfield’s advocacy for the convergence of biology and engineering helped pave the way for both the building itself and the research approach within—the combination of which, as Hammond pointed out, has made the Koch Institute the site with the highest rate of intra-MIT co-authorship as well as the top inventing building on campus. We are grateful for Hockfield’s championship and proud that our “backyard” will bear her name.


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A Few Bad Apples

Hynes Lab researchers present the most comprehensive analyses to date of the extracellular matrix (ECM) of pancreatic cancer. Their findings, published in Proceedings of the National Academy of Science, reveal previously unknown molecular changes during cancer progression in both mouse models and human patients, and distinguish ECM proteins produced by tumor cells from those produced by stromal cells—the dense and fibrotic connective tissue that surrounds and interweaves tumors. Although stromal cell-derived proteins comprise the bulk of the tumor ECM, it is actually a set of tumor cell-derived proteins that correlate most strongly with poor patient survival. These findings may help explain why previous strategies for general depletion of the stroma added to poor patient outcomes, and suggest more precise ECM manipulations as pancreatic cancer treatments.


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KI Executive Director Steps Down

Anne E. Deconinck, PhD bids farewell to the Koch Institute, where she has served as Executive Director for seven years. In this role, Deconinck has overseen various outreach efforts including external collaborations, industrial and clinical partnerships, communications, and community building. Throughout her 17-year tenure in research administration at MIT, she has been a dedicated proponent of interdisciplinary research approaches and basic science. Deconinck is leaving to pursue new opportunities in industry. A search for the next Executive Director will commence this fall.

Bhatia and Young Elected to the National Academy of Medicine

Congratulations to KI faculty members Sangeeta Bhatia and Richard Young on their election to the National Academy of Medicine. Bhatia was honored for “pioneering small-scale technologies to interface cells with synthetic platforms.” She is one of only 25 individuals who have been elected to all three National Academies—a distinction shared with our own Paula Hammond and Robert Langer. Young was honored “for fundamental insights into gene control in human health and disease, invention of widely used new technologies, and the development of novel therapeutics for cancer.”

 

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Vaccine with a Double STING

A new vaccine from the laboratory of KI faculty member Daniel Anderson targets mRNA to immune cells using lipid nanoparticles. The nanoparticles, described in Nature Biotechnology, protect antigen-coding mRNA from breaking down in the injection site and guide the payload to antigen-presenting immune cells that will in turn attract and stimulate T cells and other immune cells. Further, the lipid polymers themselves boost T cell activity by activating the STING (stimulator of interferon genes) pathway. The team is working to build a library of additional immune-stimulating nanoparticle structures and screen them to identify the designs that best boost the vaccine’s effectiveness against individual cancers and other diseases.

 

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Honor Roll

Her polymeric nanomaterials may self-assemble, but for many of Paula Hammond’s students, assembling a career is no easy feat. Hammond was recognized with MIT’s Office of Graduate Education’s Committed to Caring (C2C) award. Praised for her listening skills, her ability to help students navigate MIT’s many programs, and her commitment to improving departmental diversity and inclusion, it is easy to “C2C” why Hammond was a standout choice for this honor. Hammond talks about the importance of mentorship and community for her own career in this talk given at the “Talented 12” symposium, hosted by C&EN at this year’s American Chemical Society national meeting.

Congratulations as well to KI graduate students Lauren Stopfer (White Lab), Lauren Milling (Irvine Lab), and Jared Kehe (Blainey Lab), named to the 2019 cohort of Siebel Scholars. Selected on the basis of academic achievement and demonstrated leadership, these three bioengineers join a network of more than 1,400 scholars, researchers, and entrepreneurs.

Finally, a well deserved shoutout to Koch Institute collaborator William G. Kaelin, Jr. (and his co-awardees) on winning the Nobel Prize in Physiology or Medicine for his discoveries of how cells sense and adapt to oxygen availability. In an interview with NBC News, Kaelin’s Bridge Project collaborator Matthew Vander Heiden described how these discoveries could contribute to the development of new drugs. In a less publicized editorial conversation here at the Koch Institute, he commented, “This is important work and a great moment for basic biology, and Bill is a real stand-up guy.” We agree!

Combating Drug Resistance in Pancreatic Cancer

The chemotherapy gemcitabine is among the most effective pancreatic cancer therapies, yet nearly all patients fail to respond or quickly develop resistance. A recent Cancer Research paper highlights work by the Hemann Lab, in collaboration with the Vander Heiden group, to better understand how pancreatic tumor stroma—prominent fibrotic tissue that surrounds the tumor— limits gemcitabine response. Their findings implicate a metabolite known as deoxycytidine, which is secreted by stromal cells called pancreatic stellate cells, and inhibits gemcitabine processing in tumor cells. Their work suggests that reducing deoxycytidine production in the stellate cells may increase the efficacy of gemcitabine and similar therapies. This work was supported in part by a David H. Koch Fellowship and the MIT Center for Precision Cancer Medicine; KI members Jacqueline Lees and Doug Lauffenburger are also senior authors.

 

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Trailblazers of Glory

Congratulations to KI faculty member Regina Barzilay, who won “Digital Trailblazer” at the 2019 Xconomy Awards in Boston for her widely reported work using AI algorithms for early detection of breast cancer. Now in use at MGH, the deep-learning system can predict from a mammogram whether a patient is likely to develop breast cancer as many as five years in advance.

Also of note, friend of the KI Linnea Olson won Xconomy’s “Patients First” award for her advocacy of patient-centered approaches to drug discovery and development. Olson was a patient of Jacks Lab alumna and former Charles W. and Jennifer C. Johnson Clinical Investigator Alice Shaw, and in 2013 shared with the KI community her experience with stage IV lung cancer and clinical trials. 

 

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Pod People

You’ve heard one podcast, you should hear ’em all. Tune in to these wave-worthy interviews and find out what makes our community tick:

  • Institute Professor and Nobel laureate Phillip Sharp talks with Luke Timmerman about his journey from farm field to MIT lab.
  • Paula Hammond brings her perspectives on nanomedicine, public outreach, and interdisciplinary collaboration to the Nano Tube.
  • Amon Lab graduate student Summer Morrill shares her surprising evolution from would-be genetic counselor to molecular biologist in the final episode of BioGenesis’s debut season.

In Good Company

Ome-goodness, it’s a new approach to epigenetic drugs! Flagship Pioneering announced its debut of Omega Therapeutics, which builds on work by Koch Institute members Richard Young and Rudolf Jaenisch. The company is poised to break new ground in drug development by focusing on gene expression.

Another Jaenisch-founded company, Fate Therapeutics, has been cleared by the FDA to begin clinical studies evaluating its off-the-shelf natural killer cell-based immunotherapy FT596. The tests will target multiple proteins implicated in B-cell lymphoma and chronic lymphocytic leukemia.

In other immuno-oncology news, Verseau Therapeutics has emerged from stealth mode, armed with siRNA delivery technology originally developed by Koch Institute members Daniel Anderson and Robert Langer. The company aims to tackle cancer with their first macrophage checkpoint modulator.

Foundation Medicine, Inc., whose founding scientific advisors include Koch Institute member Eric Lander, will team up with Natera, Inc. to develop and commercialize novel assays using circulating tumor DNA for cancer monitoring and personalized medicine.

 

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