The David H. Koch Institute for Integrative Cancer Research at MITThe David H. Koch Institute for Integrative Cancer Research at MIT

Massachusetts Institute of Technology

National Cancer Institute Cancer Center

Science + Engineering... Conquering Cancer Together

Going Chiral

Controlling chirality—the so-called “handedness” of a molecule’s structure—improves the performance of drug-delivering nanoparticles, according to new research from the Langer Lab. The Advanced Materials study showed that when coated in the “right-handed” form of amino acid cysteine, nanoparticles avoided destruction by enzymes and penetrated cancer cells more easily.   more...

Transforming Early Detection: More Than Meets the A.I.

KI member and computer scientist Regina Barzilay spoke with The New York Times and PBS’s FRONTLINE about how her own breast cancer diagnosis inspired her to use machine learning tools to empower physicians and patients alike. Working with physician Connie Lehman, Barzilay’s A.I. systems are improving mammography and enabling earlier detection—and prediction—of the disease. more...

Lumicell Hits the Home Stretch

KI startup Lumicell launched a pivotal trial for its Lumicell Imaging System, a final step toward FDA approval for the innovative image-guided cancer surgery technology. Supported early on by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the system was developed by KI member Linda Griffith, with MIT collaborator Moungi Bawendi and former KI administrator W. David Lee ’69. Lumicell’s system pairs an injectable contrast agent with a hand-held, single-cell resolution imager to scan surgical margins for residual cancer cells. Proprietary software produces real-time images that help surgeons take immediate action to prevent repeat surgeries, lower healthcare costs, and improve patient outcomes. more...

Co-lead author Leanne Li standing by mini-MRI used in the study.

New target for small cell lung cancer

Researchers in the Jacks and Vander Heiden labs identified a new therapeutic target for small cell lung cancer (SCLC), an especially aggressive form of lung cancer with limited options for treatment. In a study appearing in Science Translational Medicine and funded in part by the MIT Center for Precision Cancer Medicine, the team used genetic screens to search for SCLC targets that could be tested relatively quickly and easily in a clinical setting. Researchers discovered a metabolic vulnerability to the loss of DHODH, a key enzyme in the pyrimidine synthesis pathway. They also found that a DHODH inhibitor brequinar—already approved for use in patients as an immunosuppressant—slowed tumor progression and increased survival in SCLC mouse models and was effective in treating two of four patient-derived small cell lung cancer tumor models.  more...

Cell-based Therapy Squeezes into Human Trials

Paving the way for SQZ Biotech’s first human trial, the FDA accepted the company’s IND application for a cell-based therapeutic vaccine to treat HPV-positive tumors, including reproductive and head and neck cancers. SQZ’s therapies, based on research by the KI’s Langer and Irvine labs, with MIT collaborator Klavs Jensen, activate the immune system against cancer. SQZ’s signature CellSqueeze device opens a temporary hole in a cell membrane through which materials can pass, in this case inserting tumor-associated antigens into peripheral blood mononuclear cells (PBMCs). Proof-of-concept studies demonstrating the potential of both the device and a strategy using B-cells (one type of PBMC) were supported by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund. more...

Bhatia’s Biomarkers Bring Insight to the Clinic

Glympse Bio, founded by Sangeeta Bhatia, will move its early detection and monitoring strategy into patients as part of Gilead’s NASH clinical program. The Bhatia lab’s activity-based nanosensors for cancer, fibrosis, and other conditions release synthetic urinary biomarkers into the body when they encounter diseased cells. Developed in part with support from the Koch Institute Frontier Research Program, they will help determine disease stage and treatment responses in real time. NASH, or non-alcoholic steatohepatitis, is an advanced form of fatty liver disease linked to obesity and a major risk factor for liver cancer, for which there are few treatment options. more...

Introducing the 2019-2020 Convergence Scholars

The Marble Center for Cancer Nanomedicine and the MIT Center for Precision Cancer Medicine are pleased to announce the 2019-2020 class of Convergence Scholars. The Convergence Scholars Program (CSP) provides postdoctoral trainees with opportunities to further their experiences and skills beyond the research laboratory. Scholars will learn more about science project development, policy, technology transfer, education and outreach, business and finances, industry, and the clinic. more...

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 fellow KI investigators 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." more...

Golden Anniversary for Luria's Gold Medal

Fifty years ago, on the heels of a historic summer, microbiologist and MIT professor Salvador E. Luria learned he had just won the Nobel Prize. Shortly after the passage of the National Cancer Act of 1971 Luria successfully applied for funds to build a cancer research facility at MIT, overseeing its construction and recruiting scientists with expertise in genetics, immunology, and cell biology. As inaugural director, Luria and his founding faculty opened the MIT Center for Cancer Research in 1974, and quickly set the standard for investigating the fundamental nature of cancer.  Faculty members isolated the first human oncogene, discovered RNA splicing, and made numerous other seminal contributions to cancer biology and genetics, laying the groundwork for new methods to treat and diagnose cancer. In tribute to the individual who spearheaded the formation of the MIT’s first dedicated cancer research effort the Koch Institute is working, with friends and the MIT administration, to name the Koch Institute’s main meeting space the Salvador E. Luria Auditorium.   more...

Combating 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.  more...

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. more...

Holding Court

On October 4, 2019, 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 a 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 for Integrative Cancer Research. Hockfield's advocacy for the convergence of biology and engineering helped lay the foundation for this building—which, as Hammond pointed out, is 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.     Photo credit: Gretchen Ertl     more...

KI Executive Director Steps Down

Anne Deconinck 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. more...

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. more...

Koch Institute Faculty Position Available

The Koch Institute for Integrative Cancer Research, together with the MIT Department of Biology invites applications for a junior or senior faculty appointment. Appointments are expected to be in the MIT Department of Biology, but other departments in the MIT School of Science or School of Engineering will be considered, if appropriate. We are particularly interested in candidates who will help promote and provide diversity. This is an open search with regard to field of study and specific research focus, but we encourage applications related to basic biological mechanisms relevant to cancer as well as computational and machine learning approaches to cancer research. The successful candidate will have laboratory space in the Koch Institute. Candidates must hold a PhD in the biological, chemical, physical, mathematical, or computational sciences, or in an engineering field; or an MD; or equivalent terminal degree. To apply, submit application materials online. Completed applications will be reviewed starting October 1, 2019.     more...

A Triple Threat

KI member and Marble Center for Cancer Nanomedicine director Sangeeta Bhatia talks with Upworthy about her uphill climb through the worlds of engineering, medicine, and entrepreneurship, and her continued commitment to pushing boundaries as a scientist and mentor. Bhatia discusses the challenges of increasing the number of women in the STEM pipeline and credits early flexible support with helping her balance the demands the challenges of starting an ambitious research program and a new family. more...

Trailblazers of Glory

KI faculty member Regina Barzilay 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 if 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.

Congratulations to both!      more...

The Mighty Mighty Ketones

Ketone bodies—molecules produced by the breakdown of fat—promote the regeneration of stem cells in the intestinal lining, according to new work from the laboratory of Ömer Yilmaz. In a study appearing in Cell, researchers found that intestinal stem cells produced unusually high levels of ketone bodies, even in the absence of a ketogenic (high-fat) diet, and that these molecules stimulate the Notch pathway to boost stem cell production. Comparisons of diets in mice suggest that ketogenic diets may help repair damage to the intestinal lining, which can occur in cancer patients receiving radiation or chemotherapy. This research was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the MIT Stem Cell Initiative, and The Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center. more...

Turning the 'Phage on Chemotherapy

A subset of white blood cells known as macrophages play a central role in the ridding the body of unwanted cellular threats. However, some microenvironments can render macrophages inactive. Chen Lab researchers, in collaboration with investigators at the University of Southampton, set out to combat bone marrow-resident tumors that are generally resistant to treatment. They demonstrated that low doses of cyclophosphamide chemotherapy activated macrophages when combined with therapeutic antibodies. The combination cleared bone marrow-resident tumor cells, such as B cell lymphoma and breast cancers. The results, published in Cancer Immunotherapy Research, suggest that treating cancer patients with low-dose chemotherapy will not only kill tumor cells directly, but could also aid in immunotherapy via macrophage activation in resistant organs. The immunotherapeutic potential of macrophages was featured in the KI’s 2016 Image Awards exhibition. more...

In Remembrance: David H. Koch (1940-2019)

MIT alumnus and MIT Corporation life member emeritus David H. Koch has died at age 79. After receiving the SB (1962) and SM (1963) in chemical engineering at MIT, Koch joined his family’s business, Koch Industries, in 1970. He became president of Koch Engineering in 1979 and served as executive vice president of Koch Industries until he retired for health reasons in 2018.     Koch’s death follows a long battle with prostate cancer, first diagnosed in 1992. Koch has said his experience with the disease encouraged him to become a “passionate crusader” for cancer research. The Koch Institute for Integrative Cancer Research stands as a legacy to that passion. His $100 million gift in 2007 enabled MIT to establish the Koch Institute for Integrative Cancer Research and begin construction of its home in Building 76, where scientists and engineers work together under one roof in pursuit of powerful, new ways to diagnose, treat, and ultimately prevent cancer.         “David’s magnificent gift paved the way for our building, for numerous professorships held by our faculty, and for our unique approach to cancer research,” said Tyler Jacks, director of the Koch Institute and David H. Koch Professor of Biology. “I will always be profoundly grateful for his vision and generosity.     more...

The Condense-ated Version

Two new studies from the laboratories of KI members Richard Young and Phillip Sharp give a clearer picture of how specialized droplets called condensates may govern the transcription—or conversion—of DNA into RNA. Transcription relies on the coordination of multiple molecules and processes to orchestrate gene activity and regulation. Emerging research into the mechanisms behind these functions point to condensates as a key element in facilitating the necessary interactions.

In a Molecular Cell study, researchers found that weak interactions among disordered regions of transcription factors and other molecules may help determine whether a condensate forms at a stretch of DNA that regulates gene activity. Read more

A Nature study found that separate condensates form for transcription initiation and for splicing and transcriptional elongation, and that the phosphorylation of RNA polymerase II (one component of the transcription machinery) changes a protein’s affinity for one condensate type or the other. Read more.

Young and others have formed a company called Dewpoint Therapeutics to translate condensate biology into potential treatments for a wide variety of diseases, including cancer. more...

Nothing But Blue Skies

The American Institute of Chemical Engineers (AIChE) endowed a fellowship program in the name of David H. Koch Institute Professor Robert Langer. The new Langer Prizes for Innovation and Entrepreneurial Excellence award unrestricted grants of up to $100,000 to researchers in pursuit of "blue sky" ideas, with preference to those working in chemical and biological engineering. “It is my wish that these fellowships will help future innovators to achieve the big dreams — dreams that can make the world a better place,” said Langer in a video statement. The first recipients will be announced in September. Read more.   more...

Curiosity: A Tribute to Steven Keating

With deep admiration for his ready and profound intellectual curiosity, the Koch Institute notes the passing of Steven Keating SM ’12, PhD ’16, from brain cancer at the age of 31. Then a graduate student in mechanical engineering, Keating spoke about his experience with cancer as part of the Koch Institute’s with/in/sight public lecture series in 2014, shortly after surgery to remove a baseball-sized tumor from his brain.

Like many at MIT, he loved data, and he collected a great deal of his own—everything from scans to sequencing information, including 3D computer analyses he used to fabricate models of his own tumor and pilot a technique for faster, cheaper, and better modeling. In fact, it was the IDH mutation revealed by his tumor biopsy that led Keating to the Koch Institute, where Matthew Vander Heiden and Bridge Project collaborators are using 2HG, an ongogenic metabolite produced by mutant IDH, as a biomarker to detect and monitor IDH-mutant cancers. Citing the role knowledge of his previous MRI scans played in his timely diagnosis, Keating became a passionate advocate for patients to have better access to their own health information and for open-sourcing patient data to advance research on cancer and other diseases. Learn more. more...

T cells being activated with a vaccine that accumulates in the lymph nodes.

The Hitchhiker's Guide to Immunotherapy

It's no Ford Prefect, but this is one CAR-T that's going places. New research from KI and Marble Center for Cancer Nanomedicine member Darrell Irvine and fellow immune engineer Dane Wittrup, published in Science, takes advantage of the Irvine Lab's hitchhiking vaccine technology to turbo-charge T cells. By stimulating engineered cells' CARs (chimeric antigen receptors) inside the lymph node, the repurposed vaccine was able to activate and expand the population of tumor-killing T cells for a variety of cancer types, including solid tumors for which immunotherapy has previously proven ineffective. The technology has been licensed to biotechnology company Elicio Therapeutics and is expected to begin clinical tests within the next few years. So long and thanks for all the antigens! more...

defects in the mitotic spindle produced by two drugs that interfere with cancer cell division

Synergy Sleuths

The Yaffe Lab developed a software program to solve a veritable whodunnit behind a surprisingly powerful new combination of cancer drugs. Hoping to complement the DNA-damaging effect of PLK1 inhibitors, researchers tested a MTH1 inhibitor, a type of drug known to block DNA repair, and found the combination killed far more cancer cells than either drug alone without disrupting healthy cells. However, they could not confirm that the combination attacked the cancer cells' DNA repair pathways. To identify a more likely suspect, the researchers developed a program that analyzes gene expression data to track down the cellular pathways most affected by the drugs. In this case, their new analytical tool revealed that both drugs targeted the formation of the mitotic spindle during cell division, albeit in different ways. Their findings, published in Cell Systems, could accelerate the clinical use of these inhibitors for combination cancer therapy. The work was funded in part by the MIT Center for Precision Cancer Medicine, the Charles and Marjorie Holloway Foundation, and The Bridge Project. more...

Angelika Amon Named 2019 "Great Immigrant"

Many congratulations to Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, on being named to the Carnegie Corporation of New York's 2019 list of Great Immigrants, Great Americans. Released every July 4th, the list celebrates naturalized U.S. citizens who “strengthen America’s economy, enrich our culture and communities, and invigorate our democracy through their lives, their work, and their examples.” Amon, originally from Austria, made the list for her work on cell growth and division and how errors in this process contribute to cancer, aging, and birth defects. more...

2019 Karches Mentorship Prize Now Open for Nominations

The Peter Karches Mentorship Prize is awarded annually to up to four trainees (post-doctoral associates, post-doctoral fellows, and/or graduate students) serving as mentors to high school and undergraduate students, as well as to technicians with undergraduate degrees obtained in the past five years, while working in KI laboratories. 

Each laboratory in our building will be able to nominate up to two mentors for consideration for the prize and, therefore, the PIs will need to be involved in the decision-making in this process. Previous winners of the Karches Prize are ineligible for nomination. Nominations must be submitted to ki-fellowships@mit.edu by noon Monday, October 9, 2019. Winners will be announced at the KI Retreat. See prize details and nomination form here.

In addition to recognizing the contributions of trainee mentors at the KI, this prize celebrates Peter Karches’s extraordinary legacy. Mr. Karches spent his career at Morgan Stanley, rising to become president and chief operating officer of Morgan Stanley’s institutional securities and investment banking group. A passionate horse racing fan, he bred and raced thoroughbreds, and co-chaired the New York Racing Association. After a long battle with chronic lymphocytic leukemia, Mr. Karches passed away in April 2006. In honor of Mr. Karches’s generosity, intellect, and steadfast commitment to family and friends, James Goodwin, a close friend of the Karches family, has established the Peter Karches Mentorship Prize at the KI.             more...

Unmasking Mutant Cancer Cells

Researchers in the Jacks and White Laboratories have identified a new dosing routine for a well-studied class of anti-cancer drugs that makes tumor cells more easily recognizable to the immune system. The team found that trading traditional bolus dosing for sustained, low-level dosing of heat shock protein (HSP) inhibitors increased the number of mutated protein fragments presented on the surfaces of tumor cells. Their approach, described in Clinical Cancer Research, could improve immunotherapy's effectiveness across more cancer types with fewer side effects and reinvigorate clinical investigations of promising HSP inhibitors. The research was inspired by and builds on work, partly supported by the Koch Institute Frontier Research Program, of late MIT biologist and KI member Susan Lindquist. more...

Taris Touts Trial Success

Taris Biomedical, founded by David H. Koch Professor of Engineering Michael Cima and David H. Koch Institue Professor Robert Langer, has made exciting headway in translating its approach to treating muscle-invasive bladder cancer. TAR-200 is an implantable device developed by the Cima and Langer Labs that continuously administers gemcitabine, a chemotherapy drug, for multiple weeks. First, Taris shared positive results from an ongoing study of the device alone, which suggest therapeutic benefit to both patients who undergo radical cystectomy and those unfit for surgical intervention. Two weeks later, the company announced the dosing of the first patient in a new clinical trial, in collaboration with Bristol-Myers Squibb, that combines the device with nivolumab, an approved cancer immunotherapy. more...

Mouse melanoma tumor slice with collagen-binder anchored to collagen surronding

Killing Tumors with Cytokine-ness

Immune cell signaling proteins, known as cytokines, are highly toxic—not just to tumors but, unfortunately, to healthy tissue as well. Wittrup Lab researchers are delivering cytokines directly into solid tumors and using the collagen-binding protein lumican to confine these cell-killing proteins within the tumoral space. Their strategy, described in Science Translational Medicine, leverages the protective layer of collagen produced by the cancer cells to prevent leakage of these toxic agents into the bloodstream and opens up previously-closed avenues for combination immunotherapy. Read more. more...

Give Her an Inchworm, She'll Go the Extra Mile

Ritu Raman and her inchworm-like creations were honored by MIT Technology Review in their annual celebration of "35 Innovators Under 35." A postdoc in the laboratories of Michael Cima and Robert Langer, Raman combines traditional and biological materials to create robots and machines that interact with their environment and take action. Her 3D-printed biohybrid designs have the potential to improve both human and environmental health.  Learn more about biohybrid design in Raman and Langer's review article in Advanced Materials and read her reflections on her career in this interview with HubWeek. more...

Compound Interest

Researchers in the laboratories of KI faculty members Michael Hemann and Graham Walker discovered a compound that may make cancer cells more susceptible to cisplatin and similar cancer therapies on the first and, importantly, subsequent doses. Cisplatin and drugs like it work by severely damaging the DNA of cancer cells, which have often lost one of the more reliable means of DNA repair. The newly-identified compound, known as JH-RE-06, interferes with a key component of translesion synthesis, a less accurate DNA repair pathway that not only helps cells survive chemotherapy, but introduces mutations that might confer resistance to future treatment. The study, appearing in Cell and funded in part by the MIT Center for Precision Cancer Medicine, found that the combination killed many more cells than cisplatin alone and that surviving cells were far less able to generate new mutations. more...

Backpacks on the Fast Track

Torque Therapeutics, founded by KI Associate Director Darrell Irvine, has fast-tracked its Deep-Primed T cell immunotherapy program, potentially expediting approval for its use for patients with relapsed or intractable solid tumors and lymphomas. Currently in clinical trials, the technology attaches nanoparticle "backpacks" to T cells that have been programmed to target and attack tumors. The backpacks deliver immune-stimulating drugs that help T cells survive and function while avoiding some of the toxic side effects that come with systemic delivery of drugs. more...

Scholar of Repute

Congratuations to KI faculty member Stefani Spranger, one of seven researchers selected as a 2019 Pew-Stewart Scholar for Cancer Research. Jacks Lab alum Michel DuPage and Hemann Lab alum Luke Gilbert were also selected. A partnership between the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust, the scholarship program supports researchers pursuing groundbreaking work focused on better understanding the origins, diagnosis, and treatment of cancer. Spranger will use the four-year grant to examine how the makeup of patients’ tumor immune microenvironment contributes to their response to immunotherapy. Additionally, Spranger received a 2019 Young Investigator Award from The Melanoma Research Alliance. more...

Accelerating Healthcare Solutions with David Lee

David Lee (1969) returned to MIT 40 years after graduation to develop low-cost, high-impact healthcare solutions. The work he has done in the 15 years since will have a tremendous impact on the treatment of patients with sepsis, transplants, and several forms of cancer. More immediately, it’s the topic of a presentation Lee will give as part of Tech Reunion 2019, to mark his 50th class reunion.  From old school skills to next generation devices, business to bedside, hear how Lee's MIT collaborations (and support from the Koch Institute Frontier Research Program) helped him begin a second career, found two businesses, and impact people’s lives for the better. He presents, “Accelerating healthcare solutions: Re-engaging in technology at MIT 40 years post-graduation,” on June 7, from 3-4:30 PM in the Koch Institute Auditorium. MIT alumni and Tech Reunion attendees welcome! more...

Better Breast Cancer Risk Prediction

A deep-learning model developed by KI member and Delta Electronics Professor Regina Barzilay can predict from a mammogram if a patient is likely to develop breast cancer within five years. Trained on mammograms and outcomes from more than 60,000 patients at Massachusetts General Hospital, the model learned to spot patterns in mammograms that are precursors to malignant tumors. Published in Radiologythe model performed significantly better than existing approaches, and could be used in the future to build personalized breast cancer screening plans. Read more.

At last month's SOLUTIONS with/in/sight, Barzilay was joined by her co-author, Harvard Medical School Professor and Director of Breast Imaging at Massachussetts General Hospital Constance Lehman, to talk about the new model and earlier work using deep-learning models to screen for dense breast tissue. Managing Director of The Boston Globe and STAT Linda Pizzuti Henry moderated the discussion, with an introduction from MIT president emerita and KI faculty member Susan Hockfield. Watch videomore...

Guiding Light

A new system developed by the laboratory of KI member and James Mason Crafts Professor Angela Belcher could pinpoint ovarian tumors during debulking surgery and improve survival rates for patients. Most ovarian cancers are diagnosed in advanced stages of the disease, after tumors—often quite small—have spread so abundantly throughout the abdomen that it is difficult for a surgeon to remove them all. In a mouse study led by Mazumdar-Shaw International Oncology Fellow Neelkanth Bardhan and published in ACS Nano, researchers identified tumors as small as 0.2 millimeters with a combination of near-infrared light and single-walled carbon nanotubule probes. Researchers are seeking approval for a FDA phase 1 clinical trial for the system and plan to adapt it for monitoring patients for recurrence of tumors and for early-stage diagnosis of ovarian cancer. The system was developed with support from the Koch Institute Frontier Research Program and later tested with support from the Bridge Project. more...

Your Summer Reading Is Here

Susan Hockfield's book, The Age of Living Machines has officially hit the bookshelves. Offering a glimpse into a possible future driven by the convergence of biology and engineering, Hockfield describes how researchers at the KI, MIT, and beyond are assembling the "biological parts list" developed from 20th-century revelations in molecular biology and genetics into a stunning array of "living machines" to solve some of the most important—and difficult—challenges of the 21st century. Get a sneak peek into this exciting new book at MIT News or on WGBH's Greater Boston. more...

 Aneuploidy in Prostate Cancer

Prostate cancers with higher levels of aneuploidy—an abnormal number of chromosomes—also come with higher lethality risk for patients, according to a new study from a Bridge Project team co-led by Angelika Amon, KI member and Kathleen and Curtis Marble Professor in Cancer Research, and Harvard T.H. Chan School of Public Health faculty member Lorelei Mucci. Using a collection of prostate cancer tumor samples, researchers extrapolated the degree of aneuploidy from each sample's genetic sequencing information and compared it to information about patient outcomes. Patients with a higher degree of aneuploidy were five times more likely to die from the disease. The findings, published in Proceedings of the National Academy of Sciencessuggest that aneuploidy could be used to more accurately predict patients' prognosis and to identify patients who might need more aggressive treatment.  more...

Alpaca Punch

In two studies appearing in Proceedings of the National Academy of Sciences, researchers from the laboratory of Richard Hynes, KI member and Daniel K. Ludwig Professor for Cancer Research, showed how tumors and metastases could be imaged and treated with lightweight antibodies (or, "nanobodies") derived from alpacas. The nanobodies target the extracellular matrix (ECM), which plays important roles in cancer cell survival, invasion, and development, and is more genetically stable, less heterogenous, and easier to access than cancer cells. 

The researchers, led by Mazumdar-Shaw International Oncology Fellow Noor Jailkhani, built a nanobody library for ECM proteins that were abundant in the tumor microenvironment, but absent from healthy tissues. In one study, researchers treated mouse cancer models with radioisotope-labled nanobodies. PET/CT imaging revealed clearly visible tumors and metastases. In the companion study, they used the same nanobodies to develop nanobody-based chimeric antigen receptor (CAR) T cells to target solid tumors.     more...

"And the Academy and awards go to..."

...Paula Hammond, Ed Boyden, and Aviv Regev, for their election to the National Academy of Sciences. Hammond, David H. Koch Professor in Engineering and head of MIT's Department of Chemical Engineering, is being honored for her work in nanomedicine, using biomaterials to enable targeted drug delivery and self-assembled materials systems for electrochemical energy devices. Boyden, Y. Eva Tan Professor in Neurotechnology, develops new tools for probing, analyzing, and engineering brain circuits. Regev, Professor of Biology, studies the molecular circuitry that governs the function of mammalian cells in health and disease. 

...Robert Langer, the David H. Koch Institute Professor, for the 2019 Dreyfus Prize in the Chemical Sciences, awarded by The Camille and Henry Dreyfus Foundation "for discoveries and inventions of materials for drug delivery systems and tissue engineering that have had a transformative impact on human health through chemistry." This prestigious prize in chemistry and related fields was focused this year on advances that have benefited human health. Notably, Langer is the first chemical engineer to receive it.

...Sangeeta Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science, for winning the 2019 Othmer Gold Medal from the Science History Institute for adapting technologies developed in the computer industry for medical innovation and for advocacy for diversity in science and engineering.

...Angela Koehler, the Goldblith Career Development Professor in Applied Biology, for receipt of the NSF CAREER Award. The award will support her work designing and synthesizing new chemical compounds that can change the "master program" that turns genes on and off in a cell. Koehler also won the MIT School of Engineering's 2019 Junior Bose Award for Teaching Excellence.

...Regina Barzilay, the Delta Electronics Professor, for making the "Top 100 AI Leaders in Drug Discovery and Advanced Healthcare" compiled by Deep Knowledge Analytics. more...

Row, Row, Row Your Bot

Microrobots developed by Bhatia Lab researchers swim through the bloodstream with a payload of nanoparticles in their wake. Inspired by the flagella of bacteria, researchers equipped microbots with helical propellers and placed them in a fluidic model designed to simulate disease-like environments. When an external magnet is applied, the micropropellers rotate, generating flow disruptions that drag nanoparticles along with them. Researchers also conscripted the iron oxide-producing bacteria Magnetospirillum magneticum to generate the wake. Their findings, described in Science Advances, could help overcome the challenge of moving drug-carrying nanoparticles out of blood vessels and into tumors or other target tissues.  more...

What's On Your Plate?

Cancer cell metabolism—as well as tumor growth and drug sensitivity—is profoundly influenced by the nutrient profile of the surrounding microenvironment. However, according to new research from the laboratory of KI member Matthew Vander Heiden, the nutrient composition of tumor interstitial fluid is significantly different from the plasma that feeds normal cells. Research in mice also shows variation based on diet and tumor location and site of origin. The findings, published in eLife with former KI postdoc Alex Muir as co-senior author, suggest that model cancer cells grown in media that more closely replicate physiological nutrient levels might better predict which genes are essential to tumor metabolism. The research was funded in part by the MIT Center for Precision Cancer Medicine and the Ludwig Center for Molecular Oncologymore...

New Images in Bloom

On the first day of spring, the 2019 Koch Institute Image Award winners unveiled the latest visuals to grace the lightboxes in the Koch Institute Public Galleries. Featuring a range of topics from developmental biology to machine learning, the ninth annual exhibition celebrates the diversity of MIT's biomedical research and the many fields that contribute to our understanding of cancer and the fight against it. View the images in Cell Picture Show, see photos and presentations from the opening event, or read more in STAT. more...

In Like a Lion

This spring, KI faculty member Susan Hockfield continues to champion causes for which she has a long-standing passion—the convergence of the life, physical, and engineering sciences, the advancement of women in the sciences, and support and funding for the research community.     Hockfield has penned a new book on convergence, The Age of Living Machines, which she will discuss with NPR and WBUR host Robin Young at a KI public event on May 16. Register now!         Last month, Hockfield spoke at the American Museum of Natural History in New York City, at the launch of the Lyda Hill Foundation’s IF/THEN initiative to inspire girls to consider STEM careers.         Hockfield also received the Geoffrey Beene Foundation Builders of Science Award, one of Research!America’s 2019 Advocacy Awards recognizing individuals who advance research and public health to benefit individuals worldwide.     more...

A Tale of Two Acidities

Scientists have long understood that an acidic microenvironment is associated with more aggressive cancer cells, and have attributed tumors' higher acidity to its oxygen-deprived interior. However, a study led by KI faculty member Frank Gertler mapped acidic regions to the tumor surface as well as to its interior. In a paper appearing in Cancer Research, researchers also showed that acidic cells ramped up production of proteins that promote invasion and metastasis and that this process could be reversed in mice by making the tumor environment less acidic.  more...

But what he really wants to do is direct...

Tyler Jacks, cancer researcher, mouse model pioneer and now...movie star? Jacks lends his voice and reflections to Breakthrough, a brand new documentary about 2018 Nobel Prize winner (and 2019 KI Summer Symposium keynote speaker) Jim Allison. Fresh off its SXSW premiere showing and follow-on screening at the AACR annual meeting, the documentary hits MIT this coming June. Stay tuned for details, and in the meantime, read more in The Washington Post and The Daily Mail. more...

Amon to Co-Direct Alana Down Syndrome Center

KI faculty member Angelika Amon will co-direct the new Alana Down Syndrome Center, which will be established at MIT's Picower Institute for Learning and Memory with a $28.6 million gift from the Alana Foundation. Amon's lab will bring its expertise in aneuploidy and chromosomal instability in cancer to the study of Down Syndrome, a condition characterized by extra genetic material from some or all of chromosome 21. Read more or watch a video. more...

TGI Pi Day

The Koch Institute’s first ever Pi Day Challenge was a success, thanks to all who participated! 135 donors stepped up, unlocking Jim Goodwin’s challenge gift and ultimately raising more than $20,000 for the Koch Institute Frontier Research Program. The program launches early-stage, proof-of-concept research with the potential to have major impact on cancer detection, treatment, and monitoring. With Frontier’s annual request for research proposals coming up, it is never too late to contribute—we rely on gifts all year round to support our most innovative cancer research projects. more...

The Building Blocks of Creative Chemistry

A Chemical & Engineering News profile of David H. Koch Professor of Engineering Paula Hammond traces her passion for chemical engineering, from her early fascination in high school with the creative potential of chemistry to her current work here at the Koch Institute. Hammond harnesses electrostatic properties of materials to build nanoparticles that address a vast array of engineering problems, from storing electochemical energy to timing and targeting the delivery of cancer drugs.

Of course, as a longtime mentor to students and, currently, the head of MIT's Department of Chemical Engineering, Hammond's recognition of the power of multiple perspectives is not limited to the nanoscale. "Excellence is gained from diversity," she says, which helps us "make inroads into difficult problems because we put together people who have different ways in which they approach problems."  more...

Myc Drop

A research team led by KI faculty member Angela Koehler developed a strategy for reducing the activity of Myc, one of the most common, but notoriously difficult to target cancer-promoting genes. Scientists have tried–and failed–for decades to develop drugs that block the Myc protein, which is overexpressed in about 70% of cancers. In a study appearing in Cell Chemical Biology, researchers discovered a new compound that ties up Myc's binding partner, Max. The compound stabilizes bonds between two Max molecules, leaving unpartnered Myc molecules to be broken down within cells. The compound, which the study found to suppress tumor growth in mouse models, has been licensed by Kronos Bio for further study and development.  more...

Taking a Deep Dive with DOLPHIN

DOLPHIN, a non-invasive imaging system from the laboratories of KI faculty members Angela Belcher and Paula Hammond, uses near-infrared light to find tiny tumors no more than a few hundred cells large. In a study appearing in Scientific Reports, researchers used their imaging system to track a 0.1-millimeter fluorescent probe through the digestive tract of a living mouse. The study also showed that DOLPHIN (which stands for "Detection of Optically Luminescent Probes using Hyperspectral and diffuse Imaging in Near-infrared") can detect the probes to a tissue depth of 8 centimeters–about 5 centimeters deeper than any existing biomedical optical imaging technique. The researchers are adapting their imaging technology for early diagnosis of ovarian and other cancers that are currently difficult to detect until late stages. The study was led by Mazumdar-Shaw International Oncology Fellow Neelkanth Bardhan, and was supported by the Koch Institute Frontier Research Program and the Bridge Projectmore...

BE the Change You Want to See

KI faculty member Angela Belcher, the James Mason Crafts Professor, will be the next head of MIT's Department of Biological Engineering (BE). Her research spans multiple areas and focuses on harnessing nature’s processes in order to design technologically important materials and devices for medicine, energy, and the environment. When Belcher's appointment begins on July 1, the MIT School of Engineering will have a record high number of women leading departments (four of eight), among them fellow KI faculty member Paula Hammond, head of the Department of Chemical Engineering and David H. Koch Professor of Engineering. Belcher's KI and BE colleague Scott Manalis, the Andrew and Erna Viterbi Professor, will support her as associate department head.  more...

Spectrum of Opportunity

In an MIT Spectrum profile, KI faculty member Stefani Spranger talks about the advantages and challenges of building a lab at the forefront of cancer immunotherapy research. Like many new labs, Spranger's interdisciplinary team has the opportunity to explore a range of investigative approaches, but hasn't yet had time to build up funding, name recognition, and other resources to support them in their work. That's where an endowed professorship, such as Spranger's appointment last year as the Howard S. (1953) and Linda B. Stern Career Development Professor, can make a big difference.  more...

Acoustic Cell

Manalis Lab researchers have devised a way to use acoustic waves to measure changes in stiffness as cells go through the cell division cycle over several generations. Appearing in Nature Methods, the technique adapts the laboratory's signature mass-measuring technology and can be used to study biological phenomena such as programmed cell death or metastasis. It could also be combined with mass and growth rate measurements to predict how individual cancer patients will respond to particular drugs.  more...

All That and a Bag of MicroColonyChips

Measuring the toxic effects that chemical compounds have on cells is critical for developing cancer drugs and in fields like environmental regulation. The current gold-standard cell toxicity test, the colony formation assay, is time-consuming and labor intensive, while quicker tests sacrifice accuracy and sensitivity. The MicroColonyChip retains the sensitivity of the colony formation assay, but is fast and fully automated, delivering data in days rather than weeks. The chip was recently developed by the Engelward laboratory, in part using code developed by KI faculty member Sangeeta Bhatia and former KI postdoc and Mazumdar-Shaw International Oncology Fellow David K. Wood. The technology, described in Cell Reports, could help researchers identify and evaluate new drugs faster, advance personalized medicine applications, and support regulatory use. Leona Samson, KI faculty member emerita, also contributed to the work.  more...

Better Mammography through AI

Regina Barzilay's work using AI algorithms for early detection of breast cancer was highlighted in a New York Times feature about technology and health care. With current diagnostic tools, it is difficult to determine if a suspicious lesion seen in a mammogram is high risk, benign or malignant, leading to false positive results that then lead to unnecessary biopsies and surgeries for thousands of women annually. Barzilay's system, now in use at MGH, uses machine learning to detect similarities between a patient’s breast and a database of 70,000 images for which the malignant or benign outcome was known. You can hear Barzilay talk about her work in interviews with WBUR and CNBC. Barzilay co-chairs the KI's summer symposium about machine learning and cancer on June 14. more...

Tortoises All the Way Down

A new oral insulin delivery capsule could one day replace daily injections for people with type 1 diabetes. Developed by a team led by KI faculty member Robert Langer and longtime collaborator Giovanni Traverso, the capsule, made of stainless steel and biodegradable polymer components, injects a small needle made of compressed insulin into the stomach wall before passing harmlessly through the digestive system. To make sure that the pill lands in the correct orientation to the stomach wall, the researchers developed new device designs that were inspired by the shape of the leopard tortoise, whose angled shell ensures it can roll back on its feet no matter how it falls. In a study published in Science, researchers showed that the capsule could deliver other protein drugs that, like insulin, are too large or delicate to be absorbed undamaged by the digestive system. The team is working with Novo Nordisk to refine the technology and optimize its manufacturing process. more...

Sizing Up Cells

Why are cells of the same type all the same size? In a study published in Cell, researchers in the laboratory of KI member Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, grew yeast and human cells to several times their normal size and found that the cells' transcription machinery could no longer make enough RNA and protein to support normal function. The team's experiments also uncovered that this process contributes to loss of cell function when cells become senescent.  more...

Lung Microbiome Corrupted in Cancer

A new Cell paper from the Jacks Lab shows how lung cancer can co-opt crosstalk between the lung’s microbiome, or resident bacteria, and the immune system. Generally, resident bacteria in the lung are stable and in relatively low abundance, but in cancer, the system is disrupted. The overall population of bacteria increases, but the diversity of types of bacteria is reduced. Immune cells called gamma delta T cells proliferate and produce cytokines, or signaling molecules, ultimately promoting inflammation and tumor growth and survival. As lung bacteria become more disrupted the cycle intensifies, creating a feedback loop that supports tumor development and progression. Findings from this study have important therapeutic implications, both for breaking the feedback loop via drugs targeting key cytokines or bacterial strains and for intercepting lung cancer by managing the lung bacteria in early-stage or high-risk populations. Read more. more...

Angelika Amon wins 2019 Vilcek Award

Many congratulations to KI member Angelika Amon on winning a 2019 Vilcek Foundation Prize in Biomedical Science. The prize honors immigrant scientists whose contributions have “extraordinary implications for our understanding of human biology and our prospects for treating human disease.” Amon's work has provided crucial insights into cell growth and division, and how errors in these processes contribute to birth defects and cancer. She and her fellow prizewinners will be honored at a gala in New York this spring.  more...

Lunch Lines of Inquiry

Thanks to a fortuitous connection in the Koch Café, it is now possible to longitudinally study cancer progression and treatment response in genetically engineered mouse models using circulating tumor cells. A new microfluidic platform, described in Proceedings of the National Academy of Sciences, combines expertise from the Manalis, Jacks, Shalek, and Vander Heiden Lab to capture and genomically profile these vanishingly rare cells from a single awake mouse without depleting the animal’s limited blood supply.  more...

Just Breathe

A truly inspired combination of messenger RNA with a degradable polymer from the KI’s Anderson and Langer labs may make inhalable mRNA treatments for lung diseases possible. Once inside a cell, mRNA can induce cells to produce disease-fighting proteins, but its therapeutic potential is limited by how quickly and easily the body can break it down. In a proof-of-concept study appearing in Advanced Materials, researchers successfully delivered the combination of mRNA and stabilizing polymer to lung cells in mice using an inhalable mist. The work was partially supported by TranslateBio, which has begun testing an inhalable form of mRNA in a Phase 1/2 clinical trial in patients with cystic fibrosis. Listen in at Scientific American or read more at MIT News. more...

The Medium Matters

The Atlantic outlines scientists’ growing realization that the widespread use of generic cell culture media for cancer research may have inadvertently skewed outcomes of animal cell studies for decades. In its examination of the recent push to create media that better reflect the chemical profiles of the cellular environment, the piece highlights KI member David Sabatini’s 2017 study that showed cancer cells are much less responsive to the chemotherapy drug Adrucil when grown in a medium that more closely replicates the nutrients in human blood. Former KI postdoc Alexander Muir also gets a nod for recent work that points to limitations even in these new, more realistic media. The study, which was carried out in the laboratory of KI associate director and MIT Center for Precision Cancer Medicine member Matthew Vander Heiden, shows that nutrient levels of the fluid inside a tumor differ from those in the blood.  more...

Beyond Cancer Genomics

In an essay for Science Signaling, KI faculty member Michael Yaffe, the David H. Koch Professor of Science, makes a case for looking at cancer not as a disease of genetics, but as a disease of signaling. Yaffe argues that although genetic approaches have resulted in extraordinary insights into the disease, signaling information should be incorporated into the clinical decision-making process. He advocates for improving protein-based measurement technologies to analyze tumor cell signaling in clinical samples. This emphasis on expanding the cancer research focus from genetics to a broader program is echoed by other researchers and initiatives at MIT. For example, at MIT’s Center for Precision Cancer Medicine (which Yaffe directs), researchers explicitly incorporated non-genomic approaches into the fundamental mission and research portfolio. more...

Headphone Jacks

Tyler Jacks sat down with Transnetyx founder and CEO Bob Bean to share his path to cancer research and his insights into building a career in science, the power of mentorship, and putting together a great lab. Listen in at the Highly Cited podcast. more...

Festschrift for Bob

Bioengineering & Translational Medicine published a tribute issue (a.k.a. “festschrift”) in honor of the KI's own Bob Langer and fellow chemical engineering luminary Nicholas Peppas on behalf of the American Institute of Chemical Engineers and its Society for Biological Engineering. In the issue’s foreward, KI alumnus Aaron C. Anselmo writes that their work has “advanced the visibility of drug delivery and biomaterials in the scientific landscape, especially within chemical engineering, and has inspired young professionals to follow their paths.”  more...