News Archive: 2014

Two new Rhodes Scholars with KI connections

The 2015 class of Rhodes Scholars includes three members of the MIT community, two of whom have close KI ties. Since his freshman year, senior biology major Elliot Akama-Garren has been an undergraduate researcher in KI Director Tyler Jacks's laboratory, where he studies the therapeutic potential of T cells in suppressing lung cancer. While at Oxford, he plans to pursue a master’s degree in integrated immunology before returning to the U.S. to begin MD-PhD studies. Senior chemical and biological engineering major Anisha Gururaj has worked with the Langer Lab and, more recently, with KI faculty member Michael Yaffe to design a low-cost, nonelectric fluid warmer for military trauma victims. At Oxford, she plans to pursue master’s degrees in engineering science research and public policy. more...

Curiouser and curiouser

In 2007, Steven Keating had his brain scanned out of sheer curiosity—he wanted to see what his brain looked like. While the scan showed nothing too out of the ordinary, his persisting interest in his brain would ultimately lead to the detection of a baseball-sized tumor that was removed this past August. Now a graduate student in the Department of Mechanical Engineering and based at the MIT Media Lab, Keating says that his curiosity saved his life and that his experience with cancer has fueled a strong interest in advocating for open sourcing health data. He spoke at the KI in October to share his story as part of a SOLUTIONS: with/in/sight event on IDH-mutant cancers. more...

Crucial convergence

KI member Phillip Sharp, Nobel laureate and Institute Professor, writes about MIT's history of convergence and the changing way we "do science." In the School of Science’s fall newsletter, he discusses the importance of bringing faculty and students together from the life sciences, physical sciences, mathematics, and engineering to tackle the world's growing challenges. As Sharp writes, “Convergence does not mean that different fields of study merely share their tools, but rather that the fields come together to re-conceptualize approaches to research and solving problems.” He cites the KI as an example, when in 2008, cancer biologists from MIT’s Center for Cancer Research joined engineers from the School of Engineering to create this new institute on campus. more...

Margarita Siafaca to retire at the end of 2014

Margarita Siafaca has been an integral part of MIT’s cancer research community since its formal inception. After 40 years in this community, Margarita, the Sharp Lab’s administrative lab manager, has decided to retire from MIT at the end of December. more...

Guiding light

While aptamers—single-stranded nucleic acids—offer promise as drug-delivery tools for cancer treatment, it has proven difficult to get them to tumor cells at therapeutic levels. Now, researchers in the laboratories of Robert Langer, the David H. Koch Institute Professor and member of the Koch Institute, and Daniel S. Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital, describe in the Proceedings of the National Academy of Sciences how a new light-triggered strategy can provide more accurate control over where aptamers accumulate. This strategy holds promise for using light triggering to improve the accuracy and effectiveness of drug delivery, especially as aptamers can be attached to a variety of therapeutic agents and delivery devices, including chemotherapy drugs, siRNA, and nanoparticles. more...

Bhatia’s disruptive technology nabs international acclaim

Koch Institute faculty member Sangeeta Bhatia has been selected as one of Foreign Policy magazine’s 100 Leading Global Thinkers of 2014 for her work developing inexpensive and noninvasive diagnostics for the early detection of colon cancer. The annual list identifies top minds with translational ideas in politics, business, technology, the arts, and the sciences that have the potential to impact millions around the world. This year’s list has a particular focus on disruptive ideas and technologies. The honorees were recognized at an event in Washington, D.C., where U.S. Secretary of State John Kerry was the keynote speaker. Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, was specifically recognized for developing a diagnostic driven by nanoparticles and a simple, inexpensive, paper-strip urine test that can reveal the presence of cancer within minutes. more...

The inside story: Implantable technology improves treatment

Working on implantable devices for drug delivery, KI member Michael Cima, David H. Koch Professor of Engineering, hopes to make cancer treatments safer, more effective, and more convenient. As these implantable devices advance toward the clinic, so does the promise for improving patient outcomes and experiences. more...

In fond remembrance

The KI community mourns the loss of Herman Eisen, a professor emeritus of biology and founding faculty member of the MIT Center for Cancer Research (CCR), who died Nov. 2 at age 96. Over a 70-year career, Eisen forged a path as a pioneering immunologist whose research has significantly shaped the field. He joined the MIT faculty in 1973, having been recruited by CCR founder Salvador Luria. Eisen retired from MIT in 1989, albeit only in the official sense: As a professor emeritus, he maintained an active laboratory and continued to advise students and postdocs, research, and publish until his very last day. “Herman was a true treasure: an inspiring colleague, a caring mentor, and a wonderful human being,” says Tyler Jacks, director of the Koch Institute and David H. Koch Professor of Biology. “We all aspire to be Herman Eisen.” more...

Life lessons from 34 years of fighting cancer

At TEDxCambridge in September, Koch Institute Director Tyler Jacks shared insights from his 34 years in the "maze" of cancer research. more...

Genome-editing technique speeds analysis of genes mutated in tumors

Cancer genome sequencing has revealed thousands of mutations linked with the disease, but identifying these cancer-driving mutations is an arduous process. It generally involves sifting through a deluge of data and developing mice that model a specific mutation, a process that can take a year or more. Now, researchers from Tyler Jacks’s lab have developed a new approach to rapidly model genetic mutations in mice by using the genome-editing technique CRISPR. The researchers, including co-lead authors Francisco Sanchez-Rivera and Thales Papagiannakopoulos, used their approach to examine individual genes’ roles in lung tumor growth. By modeling APC, a tumor-suppressor gene linked to colon cancer whose role in lung cancer is not well understood, they found that APC loss does indeed drive lung tumor progression. The researchers envision that this technique could one day be used to quickly and effectively study personalized treatment options for cancer patients by modeling mice based on the genetic profile of an individual patient’s tumor. more...

Oct. 22 webinar from the Koch Institute and Cell Signaling Technology - Targeting Cancer Pathways: Tumor Resistance

The Koch Institute and Cell Signaling Technology are proud to present this webinar, the first in a series focusing on the pathways that allow for cancer development and progression, the emerging research in identifying and targeting these pathways, and the innovations in the development of cancer treatment options. more...

Swallowing your next injection

Scared of needles? When it’s time for your next shot, imagine if you could simply swallow a pill instead. MIT researchers from the labs of KI member Robert Langer, the David H. Koch Institute Professor; KI member Daniel Anderson; and Daniel Blankschtein, professor of chemical engineering, have developed an ingestible drug capsule coated with tiny needles that can safely and painlessly inject drugs directly into the stomach lining. In fact, they found that this microneedle pill can deliver drugs more effectively than subcutaneous injection. The researchers tested their pill with insulin and predict that this modular platform will be most useful for delivering drugs to treat cancer, arthritis, and Crohn’s disease. Lead authors on this paper, which appeared in the Journal of Pharmaceutical Sciences, were Giovanni Traverso, Carl Schoellhammer, and Avi Schroeder. more...

Predicting the future with amino acids

Pancreatic cancer is too often detected in late stages and with a poor prognosis. While early detection is still a major hurdle to overcome, KI member Matthew Vander Heiden, the Eisen and Chang Career Development Professor, and collaborators from Dana-Farber Cancer Institute and the Broad Institute, have found that elevated levels of three amino acids, known as the branched chain amino acids, are an accurate predictor of pancreatic cancer diagnosis. Even blood samples taken from patients up to 10 years before diagnosis revealed evidence of protein breakdown and dysregulated metabolism. While researchers must examine why this early breakdown occurs and determine if this amino-acid signature could definitively be used for early diagnosis, these findings offer promise for cancer therapeutics that target metabolic pathways. more...

Koch Institute Member Awarded $500,000 Lemelson-MIT Prize

Dr. Sangeeta Bhatia, biomedical engineer and faculty member at the Koch Institute for Integrative Cancer Research at MIT, is the recipient of the 2014 $500,000 Lemelson-MIT Prize. Bhatia is recognized for designing and commercializing miniaturized technologies with applications to improve human health. The Lemelson-MIT Prize, celebrating its 20th year, honors outstanding mid-career inventors improving the world through technological invention and demonstrating a commitment to mentorship in science, technology, engineering and mathematics. This is the second consecutive year, and third overall, in which a Koch Institute faculty member has been awarded the prize. Dr. Angela Belcher, W.M. Keck Professor of Energy, received the prize in 2013, and Dr. Robert S. Langer, the David H. Koch Institute Professor, received the prize in 1998. This also is only the fourth time an MIT faculty member has received the prize in its 20-year history. more...

Special Symposium: Bridging the Gap in Ovarian Cancer

Join us on September 16 for Bridging the Gap in Ovarian Cancer, a special symposium for ovarian cancer patients, survivors, family members, advocates, researchers, and other interested members of the public. This free public event has been organized by the Koch Institute to share and discuss advances in science and technology to fight ovarian cancer and will highlight the power of bringing bioengineering, advanced cancer science, and clinical oncology together to solve today’s most challenging problems in ovarian cancer through collaborative, interdisciplinary research. Symposium attendees are invited to stay for our evening program, SOLUTIONS with/in/sight: Women Converge on Cancer, which will take place at the Koch Institute immediately following the reception. This evening program will feature remarkable women who are staunch advocates for cancer research. (Photo by MesserWoland / CC BY-SA 3.0) more...

SOLUTIONS with/in/sight: Women Converge on Cancer

From MIT's Great Dome to the rotunda on Capitol Hill, cancer research and associated advocacy efforts are changing the lives of patients everywhere. On September 16, join three staunch advocates for cancer research to learn more about the personal journeys and powerful collaborations at the forefront of the fight against cancer. Whether forging the convergence revolution, carving out new paths for research and funding, or elevating public conversation, these inspiring leaders embody the perseverance, partnerships, and progress that move the field ever forward. more...

Talk with Vik Muniz & Tal Danino at the Galeria Nara Roesler in Sao Paulo

In a conversation with bioengineer Tal Danino at the Galeria Nara Roesler, visting artist Vik Muniz presented on the innovative research that underlies his new Sandcastles and Colonies series and the results of his MIT residency. While undertaking a residency at MIT, Muniz started taking his research into high-technology materials to the extreme in order to develop his two new series. They both combine artistic ingeniousness and cutting-edge science work by leading names such as bioengineer Tal Danino, who was Muniz’s guest for the conversation Galeria Nara Roesler hosted on August 16. more...

RNA combination therapy for lung cancer offers promise for personalized medicine

Researchers in the Jacks, Anderson, and Langer Labs report in the Proceedings of the National Academy of Sciences that they have successfully delivered nanoparticles carrying small RNA therapies in a clinically relevant mouse model of lung cancer to shrink tumors and slow their growth. They found that their nanoparticle treatment extended life just as well as a standard-care chemotherapy drug, and furthermore, that the combination therapy of the nanoparticles and the drug together prolonged life by about an additional 25 percent. “Small-RNA therapy holds great promise for cancer,” Jacks says. “It is widely appreciated that the major hurdle in this field is efficient delivery to solid tumors outside of the liver, and this work goes a long way in showing that this is achievable.” more...

New technique allows for better study of hepatitis B and drug treatments

When a hepatocyte—the main liver cell type—is isolated from the liver for study in the lab, it quickly becomes unstable. As a result, it is normally difficult to study how HBV-infected cells respond to antiviral drugs. Now, in a paper published in the Proceedings of the National Academy of Sciences, members of Sangeeta Bhatia’s laboratory at MIT and Charles Rice’s laboratory at Rockefeller University describe how to effectively stabilize these liver cells and infect them robustly with HBV, which will allow researchers to study the immune response and investigate new treatments for the virus. HBV infects about 400 million people around the world and often leads to serious complications, including liver cancer. more...

A new way to rapidly study cancer-causing mutations

In a study appearing in Nature, researchers from the lab of KI Director and David H. Koch Professor of Biology Tyler Jacks, together with Phillip Sharp’s and Daniel Anderson’s labs, have shown that they can generate liver tumors in adult mice by using CRISPR, a gene-editing tool, to disrupt tumor suppressor genes p53 and pten. This technique allows for rapid screening of these mutations and tumors’ response to treatment without needing to undergo the long and expensive process of breeding a strain of mice with a particular mutation. “The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations. The flexibility of this technology, as delivery gets better in the future, will give you a way to pretty rapidly test those combinations,” says Institute Professor Phillip Sharp. The team is now working on ways to deliver the necessary CRISPR components to other organs, allowing them to investigate mutations found in other types of cancer. more...

Dressing drug molecules in layers

David H. Koch Professor in Engineering Paula Hammond and her laboratory have refined a technique to steadily release pain medications and other drugs to a specific part of the body over a time period as long as 14 months. In a paper published in the Proceedings of the National Academy of Sciences, the researchers describe using a layer-by-layer technique to attach diclofenac, an anti-inflammatory drug, to individual layers of biodegradable, nanoscale thin-film coating. The film can be used to coat implantable medical devices or nanoparticles that can be injected into a local site. This system will reduce the need for patients to take medication frequently and, as the treatment is localized, should reduce potential side effects from medication. Researchers will now study how to best optimize this drug-delivery system for different bodily environments and other drugs. more...

Cancer Immunotherapy Gets Flashy

Pom-poms, foam fingers, umbrellas, T-shirts, whistles…all the ingredients the KI community needs to hack the immune system to fight cancer. On April 25, approximately 180 friends, colleagues, and strangers gathered to turn cutting-edge biotechnology into a larger-than-life battle behind the KI building as part of the annual Cambridge Science Festival. Documented with words and video, the third annual biology flash mob was a smashing success, educating students and adults alike about the promise of adoptive T cell transfer and cancer immunotherapy. Well, maybe not such a success for the redshirts, who, as cancer cells, suffered a rather humiliating defeat at the hands T cells' aforementioned pom-poms and foam fingers…but at least they had fun. more...

Celebrating Anniversaries at the Koch Institute

June 1974…1964…1944…cancer research historians, time travelers, and fans of the number four thrilled at the convergence of special anniversaries occurring at MIT in June 2014. This year marked 40 years since MIT’s official foray into cancer research, and we celebrated with a formal program saluting advances made by members of our cancer research community and raising a glass to the progress yet to come. Among those honored were KI members Robert Weinberg, Daniel K. Ludwig Professor for Cancer Research and director of the KI’s Ludwig Center for Molecular Oncology—who was himself celebrating his 50th undergraduate MIT reunion—and Institute Professor Phillip Sharp—who turned 70 that day. Celebrations extended into the following week, when Sharpies reconnected at the Sharp Lab’s 40th reunion. Commemorating decades of discovery in the Sharp Lab, touching speeches and hilarious musical interludes proved true Sharp’s assertion that “culture is more important than strategy.” Here’s to another well-cultured 40 years! more...

Lees & Weinberg Tackle Unanswered Questions

Jacqueline Lees, associate director of the Koch Institute and professor of biology, and Robert Weinberg, Daniel K. Ludwig Professor for Cancer Research and director of the KI’s Ludwig Center for Molecular Oncology, each tackled a still-unanswered question about cancer biology in the July issue of Scientific American. Lees weighs in on the potential role of inflammation after cancer treatment and surgery in waking up dormant cancer cells, which in turn could interact with nearby normal cells and restart a tumor. According to Lees, the right sequence of drugs could suppress this interaction. When it comes to understanding the mechanisms underlying the metastasis process, Weinberg points out that how cancer cells adapt and survive in a new tissue after leaving the primary tumor site remains unknown. He hypothesizes that this process results from significant changes in gene expression. Inquiries like these help spark the bold new cancer treatment approaches in development at the KI. more...

Small Particles, Big Collaborations

Layer by layer, Hammond Lab trainees Stephen Morton and Nisarg Shah work individually and collaboratively to develop nanoparticles for hard-to-treat cancers. Morton focuses on drug delivery (see some of his nanoparticles here), and has been part of several studies that have demonstrated progress in fighting aggressive cancers, such as a triple-negative breast cancer project with the Yaffe Lab and non-small cell lung cancer with the Jacks Lab. Shah’s work centers on bone tissue, which poses special problems for joint replacement as well as cancer treatment. In the lab, he has assembled nanolayered coatings that help new bone tissue to grow into implants, forming a tighter bond. He and Morton are now adapting that approach for nanoparticle drug delivery to bone cancer or bone metastases. Partnerships like theirs typify the KI’s collaborative approach to cancer research. more...

Langer wins Kyoto Prize, Biotechnology Heritage Award

On June 20, the Inamori Foundation in Japan announced that Robert Langer, the David H. Koch Institute Professor, won the Kyoto Prize for Advanced Technology in the Biotechnology and Medical Technology field. The Kyoto Prize is presented annually to those who have made significant contributions to the “scientific, cultural, and spiritual betterment of mankind.” Langer was specifically recognized as an interdisciplinary pioneer in the fields of medicine and engineering. He will receive his prize in Kyoto on Nov. 10. more...

YAP, YAP, YAP: Talking About Cancer Pathways

Researchers, including co-senior authors Tyler Jacks, KI director and David H. Koch Professor of Biology, and William Hahn of Dana-Farber Cancer Institute and the Broad Institute, report in Cell that in cancers driven by the oncogene KRAS, a backup genetic path could allow cancer cells to survive even if the KRAS gene were turned off. This backup path involves YAP1, a gene that produces regulatory proteins. When KRAS was turned off in cancer cells in the lab, YAP1 gene expression replaced the need for KRAS and enabled them to survive. Furthermore, the study revealed that YAP1 is necessary for KRAS-driven cells to become cancerous, and that the ability for KRAS-driven cancers to become drug resistant may result from the interaction between the two oncogenes. “This study demonstrates the importance of the complex signaling pathways that cancer cells use to stay viable and proliferate,” says Jacks. “It also shines light on the YAP pathway as a potential target of anti-cancer therapy.” more...

Sights Set on Ovarian Cancer

With her sights set on ovarian cancer, KI faculty member Paula Hammond is using her expertise in nanoparticles to develop a delivery system rapidly applicable in the clinic. “Ovarian cancer in particular is compelling to me because it’s one of the few cancers where we haven’t made real progress in 30 or 40 years, so that the death rates are still the same,” says Hammond, David H. Koch Professor in Engineering. With support from a Teal Innovator Award, and in collaboration with Massachusetts General Hospital and Dana-Farber Cancer Institute, Hammond is developing sophisticated nanoparticles to deliver siRNA and siRNA/chemotherapy treatments that will enable clinicians to provide personalized treatments for advanced stage ovarian cancer patients. In conjunction with this research, Hammond and the Koch Institute will host Bridging the Gap in Ovarian Cancer on Sept. 16, a special symposium for ovarian cancer patients, survivors, family members, advocates, and other concerned members of the public. more...

KI Symposium Celebrates RNA Renaissance

On June 13, more than 1,000 cancer researchers, RNA biologists, clinical oncologists, and others gathered at the 13th annual KI Summer Symposium to hear updates on the latest breakthroughs in the creation of RNA-based gene-editing tools and the development and delivery of RNA-cancer medicines. Recent research successes have led to renewed optimism for the use of RNA-based therapies for cancer treatment, and KI investigators and research partners are playing notable roles in this resurgence. Symposium speakers included KI members Daniel Anderson, Sangeeta Bhatia, Laurie Boyer, and Phillip Sharp. more...

Basic Research: The Bedrock of MIT

“Basic research is the bedrock of MIT—and the foundation for tomorrow.” This rationale for supporting basic research, made in the latest issue of SPECTRVM, certainly rings true at the KI. The spirit of curiosity behind basic research allows investigators to delve into unanswered problems, forging a path that connects discovery and application of knowledge. “People think of basic and applied research as separate, but it’s an extremely important mix,” says KI member Ram Sasisekharan. “To have a higher probability of success in the applied arena, it’s extremely important to be well-grounded in the basic mechanism of the targets we’re after.” more...

I Love the Bright Life

The KI has been turning heads in Cambridge’s thriving biotech community this spring. On June 5, the KI hosted a TEDxCambridge simulcast and the evening's Innovation Lab, which showcased new technologies by local innovators. Among the featured exhibitors were the Manalis and Belcher Labs, sharing new tools and devices for cancer detection and analysis with guests from all three host venues. Several hundred visitors passed through the KI Public Galleries and auditorium that night, generating buzz, tweets, and new insights about the intersection of science, engineering, and entrepreneurship. more...

Building Bridges for Award-winning Melanoma Research

A team led by KI faculty member Darrell Irvine, along with Dana-Farber Cancer Institute investigators Kai Wucherpfennig and Michael Goldberg, received the Melanoma Research Alliance (MRA) Team Science Award to optimize T cell-targeting nanoparticles for improved melanoma treatment. The Team Science Award Program is the centerpiece of the MRA research funding portfolio and aims to promote collaborative, interdisciplinary, transformational melanoma research advances with the potential for rapid clinical translation. As such, it is no surprise that this team came together through the Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center designed to unite bioengineering, advanced cancer science, and clinical oncology to solve challenging problems in cancer research and care. The team's project was among the ten finalists in this year’s round of Bridge Project funding, and speaks to the power of the Bridge Project to establish new connections between unmet clinical needs and innovative technological solutions. Congratulations! more...

Hopkins a Powerful Voice for Change

Some people use their retirement to kick back, relax, and let someone else worry about the big questions, but not former KI faculty member and Professor Emerita Nancy Hopkins. On May 18, Hopkins delivered the baccalaureate address to Boston University’s Class of 2014. She spoke to them about expectations, discoveries, and ambitions that shaped her career and encouraged them to take on challenges and campaign for social justice (read the transcript here). Hopkins, known for her crusade for gender equality as well as for her investigations into the genetic underpinnings of cancer, received both accolades and an honorary Doctorate of Science at the school's All-University Commencement ceremony. Earlier in the month, she also spoke with The Story Exchange as part of their new series, “STEM Entrepreneurship - Where Are the Women?”, discussing her passion for biology and the obstacles that female scientists face as they seek to make a difference in their field and in the world (read more). Professor Hopkins’s insightful reflections prove that at every point along the career continuum, professors influence the next generation of learners. more...

Cancer Researchers on the Up-and-Up

Congratulations to KI faculty members Daniel Anderson, J. Christopher Love, and Laurie Boyer on being awarded tenure from MIT. Both Love and Anderson hold appointments in MIT’s Department of Chemical Engineering, bringing their respective expertise in bioanalytics and biomaterials to bear on the Koch Institute's mission (read more). Boyer, an extramural KI member, is a biochemist who develops high-throughput platforms for genome analysis. The granting of tenure to these three by MIT is a testament to the quality of their research and teaching. On June 13, Boyer and Anderson will speak at the KI’s annual summer symposium, "RNA Biology, Cancer, and Therapeutic Implications."

In other promotion-related news, Forest White was promoted to full Professor in the Department of Biological Engineering, and Matthew Vander Heiden, Howard S. (1953) and Linda B. Stern Career Development Professor, to Associate Professor in the Department of Biology. Congratulations to all! more...

Expanding the Playing Field for RNA Interference

RNA interference (RNAi), a process that turns off specific genes inside cells, holds great potential for treating diseases caused by malfunctioning genes, and has shown particular success targeting genes within the liver. However, the safe and effective delivery of gene-blocking RNA to tissues beyond the liver has proved challenging. In a recent study published in Nature Nanotechnology, researchers led by KI members Daniel Anderson, the Samuel A. Goldblith Professor of Applied Biology, and Robert Langer, the David H. Koch Institute Professor, reported the most successful RNAi-mediated gene silencing in non-liver tissues to date. The engineers encased short strands of RNA, called siRNA, within newly designed nanoparticles optimized to target endothelial cells, which line most organs, and they showed successful delivery of RNA to the kidneys and heart, among other organs. They also used lower doses of RNA than previous treatments, increasing the therapy’s safety and efficiency.

These results open the door to achieving the broad potential of RNAi therapeutics, silencing disease-causing genes in many parts of the body to treat many types of disease, including cancer. more...

Double Trouble for Aggressive Cancers

KI researchers led by Paula Hammond, David H. Koch Professor of Engineering, and Michael Yaffe, the David H. Koch Professor of Science, have engineered new, “smart” nanoparticles that directly target tumor cells to deliver multiple drugs in a staggered, precisely-timed regimen.

In 2012, the Yaffe Lab showed that the timing of drug administration can make a great difference in the success of combination treatments. Yaffe’s team discovered that pre-treating tumor cells with erlotinib, a therapeutic that shuts down uncontrolled tumor growth, before administering a DNA-damaging agent called doxorubicin, is more effective than giving the two drugs simultaneously.

As part of efforts to adapt the findings for patient care, Yaffe enlisted the help of KI colleague Paula Hammond. Hammond and her team designed dozens of nanoparticles to carry Yaffe’s treatment and found that liposomes, small droplets covered in a fatty shell, were most effective. With the first drug, erlotnib, injected in the outer layer, and the second, doxorubicin, contained in the inner core, the liposomes dispatched treatment to the cells at ideal intervals as the particles broke down in the body. In the study, published in Science Signaling, this treatment was shown to effectively knock out triple-negative breast tumors and non-small-cell lung tumors in mouse models. The researchers hope to expand time-staggered treatment to other types of chemotherapy.

This work was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Fund for Cancer Research. more...

Three Companies: Sasisekharan Startups Please Crowd

“It’s about the impact we can have on patient care,” says Ram Sasisekharan, KI faculty member and the Alfred H. Caspary Professor of Biological Engineering and Health Sciences and Technology, about his biotech startups. The three companies, profiled in MIT News, combine cutting-edge bioengineering with entrepreneurial spirit and, like so many other enterprises coming out of KI laboratories, find new ways to apply academic research to real world problems. Sasisekharan’s 2006 startup, Cerulean, is one of a handful of companies using nanotechnology to treat cancer, while his latest venture, Visterra, has an eye toward global health. His first company, Momenta (originally Mimeon), transforms the sequencing of complex molecules into the development of powerful, efficient, low-cost therapeutics. All three reside within minutes of the KI and owe their success to what Sasisekharan calls a “melting pot of people, ideas, opportunities” and “the convergence of biology, analytics, computation, and engineering” within the MIT ecosystem. more...

AACR Honors KI Faculty and Celebrates National Cancer Research Month

KI faculty member and Daniel K. Ludwig Professor for Cancer Research Richard Hynes has been elected as a member of this year’s AACR Academy Class of Fellows. The AACR Academy was created in 2013 to recognize scientists worldwide whose contributions to cancer research have driven significant innovation and progress against cancer. Hynes joins fellow KI faculty members Tyler Jacks, Robert Horvitz, Phillip Sharp, and Robert Weinberg, who were inducted last year. Other members of the 2014 class include David Livingston, KI Scientific Advisory Board member and co-leader of the Bridge Project, former Board member Titia de Lange, Sharp Lab alumnus and Nobel Prize winner Andrew Fire, and several KI collaborators, including Hans Clevers, Lewis Cantley, Joan Brugge, and Stephen Elledge.

In other AACR award news, KI faculty member and Howard S. (1953) and Linda B. Stern Career Development Professor, Matthew Vander Heiden, has received the AACR Gertrude B. Elion Cancer Research Award, a one-year, $75,000 grant to support cancer research. Vander Heiden will use this award to continue his pioneering studies into the mechanisms of cancer cell metabolism, one of the breakout hot topics of this year’s AACR annual meeting.

In addition to recognizing innovative work within the scientific community, AACR is dedicated to raising public awareness about cancer research through such initiatives as National Cancer Research Month, celebrated in May every year. more...

Samson Laboratory Develops a Test to Assess DNA Repair Systems

To protect DNA against environmental attacks such as radiation, UV light, and pollutants, cells have repair systems in place, ready to patch up damaged sites as needed. If not mended, DNA injuries can lead to cancer and other diseases. KI faculty member Leona Samson and her team have developed a test to examine at least four types of DNA repair capacity simultaneously and in less than 24 hours. Previous tests have only been able to evaluate one system at a time. The test, described in the Proceedings of the National Academy of Sciences, could help doctors identify people who are at higher risk of developing cancer, predict patients’ response to chemotherapy, or determine how much radiation treatment a patient can tolerate. more...

Cima Develops a Sensor for Measuring Tumors’ Oxygen Levels

A new sensor for measuring oxygen levels around tumors has been developed by researchers from the laboratory of KI faculty member and David H. Koch Professor in Engineering Michael Cima. The sensor, described in the Proceedings of the National Academy of Sciences, is an injectable device made of silicone, which is picked up in MRI scans. The sensor is the first MRI contrast agent that can be left in the body for long periods of time, allowing for the collection of oxygen tension over several weeks. Given that cancer cells thrive without oxygen and tumors in low-oxygen environments are generally more aggressive and resistant to treatment, long-term monitoring of oxygen tension will provide new insights into tumor growth and could aid therapeutic choices and tracking of treatment response. more...

A Muti-institutional Approach to Genome-guided Cancer Medicine

Researchers from the laboratory of KI faculty member Chris Love have joined forces with investigators at the Broad Institute and clinicians at Dana-Farber Cancer Institute to develop a modular set of experimental and analytical protocols for comprehensively sequencing and confidently determining single-point mutations in the DNA of circulating tumor cells (CTCs) from prostate cancer patients. The work, published in Nature Biotechnology, demonstrates that these techniques can provide a minimally invasive window into the genetics of metastatic prostate cancer to characterize the underlying cancer and define targeted treatments for individual patients. This proof-of-concept study sets the foundation for future comprehensive surveys of CTC genomics applied to other cancer types and across a large number of samples. The work was supported in part by a TRANSCEND grant through the KI's alliance with Janssen Pharmaceuticals, Inc. more...

Triple Threat: A New Breed of Nanoparticles

MIT chemists from the laboratory of Jeremiah Johnson and researchers from the group of KI faculty member and David H. Koch Professor in Engineering Paula Hammond have come together to develop a new method for building nanoparticles that carry the drugs cisplatin, doxorubicin, and camptothecin—three drugs that are often used in a combination treatment for ovarian cancer. In a study published in the Journal of the American Chemical Society, Johnson and colleagues demonstrated that the triple-threat nanoparticles could kill ovarian cancer cells more effectively than particles carrying only one or two drugs.

Instead of building a particle and then binding a drug, the new approach uses drug-loaded building blocks that can be attached to others in a very specific structure. The team is now working on four-drug particles with the goal of developing new treatment regimens that could better target cancer cells while avoiding the toxic side effects of traditional chemotherapy. “This is a new way to build the particles from the beginning,” Johnson said. “In principle, there’s no limitation on how many drugs you can add.” more...

Great IDH-tions for Cancer Metabolism

To sustain their uncontrolled proliferation, cancer cells exploit unusual metabolic pathways. A prime example is the prevalence of mutations in the enzyme IDH in several human cancers. Mutations in the IDH1 and IDH2 genes result in unusually high production of a cancer-promoting compound called 2-HG. At this year's American Association for Cancer Research (AACR) Annual Meeting, Agios Pharmaceuticals announced very promising phase I clinical data from AG-221, an oral drug that is a selective, potent inhibitor of the mutated form of IDH2. Of seven patients with acute myeloid leukemia due to a mutation in IDH2 who were treated with AG-221, six responded to treatment, and the drug eradicated cancer cells in five of them. While these patients have only been followed for a short time and more work is needed, the encouraging data illustrate the promise of targeting cancer metabolism to develop transformative medicines. KI faculty members and cancer metabolism experts Matthew Vander Heiden and David Sabatini serve as scientific advisors to Agios.

Mutant IDH1 in gliomas is also the subject of Vander Heiden’s Bridge Project collaboration with Dana-Farber’s William Kaelin and MGH’s Daniel Cahill. Using a non-invasive imaging method known as magnetic resonance spectroscopy (MRS) to scan for 2-HG in patients bearing IDH-mutant gliomas, before and after treatment, the researchers seek to determine whether drugs targeting mutant IDH are hitting their intended mark. They are also exploring alternative strategies to treat IDH1-mutant gliomas in addition to direct targeting of the mutant enzyme. more...

SU2C Names New Innovation in Collaboration Awards in Honor of Phillip A. Sharp

Stand Up To Cancer (SU2C), a charitable initiative that draws on the resources of the entertainment industry to encourage public support of ground-breaking, collaborative, and translational cancer research, and its scientific partner, the American Association for Cancer Research (AACR), have created the SU2C Phillip A. Sharp Innovation in Collaboration Awards. "I'm humbled by the decision to name this grant in my honor," said KI faculty member and Institute Professor Phillip A. Sharp, Chairperson of the SU2C Scientific Advisory Committee. The five inaugural awards, totaling $950,000, were awarded to attendees at the 2014 SU2C Scientific Summit and announced during this year’s AACR Annual Meeting. “Never before have scientists walked into a scientific meeting with the germination of an idea, and walked out with the funding to pursue it,” remarked Sharp. Going forward, awardees will be selected annually at the SU2C Scientific Summit, granting a total of up to $1 million each year. more...

Jacks Laboratory Develops Novel Mouse Model for Aggressive Thyroid Cancer

KI researchers from the Jacks Laboratory have developed and characterized a novel genetically engineered mouse that successfully models progression from papillary thyroid cancer, which has an excellent prognosis, to anaplastic thyroid cancer (ATC), a highly lethal disease in need of therapeutic improvements. “The low incidence of the disease has hindered systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies,” says KI postdoctoral researcher David McFadden, lead author of this work and also a thyroid cancer endocrinologist at the MGH Center for Endocrine Tumors. The new model, described in the Proceedings of the National Academy of Sciences, recapitulates the hallmarks of the human disease and expands the limited repertoire of preclinical models of aggressive thyroid cancers. The study also shows that, in this model, combination treatment with MEK and BRAF inhibitors results in enhanced anti-tumor activity as compared to treatment with a BRAF inhibitor alone, suggesting that this combination could be useful as a component of treatment regimens in human ATC. The group is now taking advantage of this new mouse model to better understand why some thyroid cancers progress to ATC and get insights into mechanisms of resistance to therapies. “The goal is to stay one step ahead of the human clinical trials and be able to inform the design of these human trials with the mechanistic details learned from the mouse,” says McFadden. This work was supported by the National Cancer Institute, the Howard Hughes Medical Institute, and an American Thyroid Association Research Award. more...

KI Collaborators Edit Genes to Correct Genetic Diseases

Using a new gene-editing system known as CRISPR to replace mutated DNA with the correct sequence, KI engineers and biologists from the Anderson, Jacks, and Sharp Laboratories have cured mice of a rare liver disorder caused by a single mutation in an enzyme needed to break down the amino acid tyrosine. This collaborative work, described in Nature Biotechnology, offers the first evidence that this technology can reverse disease symptoms in living animals. The team believes that recent advances in the delivery of nucleic acid therapeutics provide hope that CRISPR-mediated correction of genetic diseases may be translatable to humans. The research was funded by the National Cancer Institute, the National Institutes of Health, and the Marie D. and Pierre Casimir-Lambert Fund. more...

Cancer Research: We're Doin’ It Right

Science spotlighted the Koch Institute in a recent article about a new breed of researchers. The feature highlights the value of interdisciplinary work in developing novel approaches for cancer detection and treatment, and demonstrates how the KI embodies a growing emphasis on cross-disciplinary training and collaborative research to tackle cancer. In particular, the article recognizes KI faculty member Angela Belcher and her work on nano-based imaging of cancerous tissue as a cheaper and more thorough method of viewing smaller tumors. It also chronicles the career of former Langer Lab postdoc Daniel Heller, who explains how his first sojourn into biomedical research, here at the KI, led him to his current position leading a cancer nanomedicine laboratory at Memorial Sloan Kettering Cancer Center. Belcher, Heller, and KI Director Tyler Jacks describe how today’s researchers, at the KI and beyond, are bringing diverse toolkits to solve problems and meet changing clinical needs. Whether one is a seasoned cancer researcher or a new arrival to the field, this article offers a powerful reminder of how transformative the mission and work of the KI truly are. more...

Biogen Idec Dedicates New Building to Phillip A. Sharp

On February 11, 2014, Biogen, now Biogen Idec, celebrated the return of its headquarters to Binney Street in Cambridge. When Biogen first opened in 1982, Kendall Square was almost deserted. Today, Kendall Square is a vibrant bioscience community clustered around MIT’s campus and densely populated by high-profile biotech companies, research institutes, and start-ups. Biogen Idec's ceremonies included the dedication of one of its new buildings to Biogen co-founder, KI faculty member and Institute Professor, Phillip A. Sharp. The honor couldn’t be more fitting: Sharp’s career, his startup Biogen, and MIT’s biotech community helped build Kendall Square and launch the area's unprecedented biotech revolution. The Koch Institute is proud to be a part of this legacy; over the last five years, KI faculty members have formed 18 new companies, many of which are located in Kendall Square.

Coinciding with this dedication, MIT News recently featured Sharp’s scientific career, his finding the perfect environment at MIT's Center for Cancer Research, and his contributions to usher in MIT's “golden age” of biology. more...

The Many Elements of Stephen Lippard

The life, career, and far-reaching scientific influence of KI faculty member Stephen Lippard were featured in the March 17th cover story of Chemical & Engineering News. The profile details Lippard’s years of innovation and mentoring, which led to his earning the 2014 Priestley Medal, the American Chemical Society’s highest award, and MIT's James R. Killian Jr. Faculty Achievement Award, among many others.

A dedicated bioinorganic chemist—and an experienced harpsichord player—Lippard has mentored more than 100 graduate students, 170 postdocs, and countless undergraduates. Lippard's multidisciplinary research spans metalloenzymes, platinum-based cancer drugs, and molecular neuroscience, and is made all the more powerful by his commitment to collaboration, in the laboratory and at home. “Many of my contributions relied upon an important collaborator to teach me things I didn’t know,” he says. While supporting students and scientists, Lippard lost his own source of support, his wife Judy, to cancer last year. “It takes a special kind of person to be married to a scientist,” Lippard reflects. more...

Two Diseases, One Drug

Studies have suggested for years that certain drugs for treating diabetes, called biguanides, are associated with anti-cancer properties. Yet, how and for whom these drugs may be beneficial remained unknown. Researchers in the laboratory of KI faculty member David Sabatini have now discovered a major metabolic pathway that provides cancer cells with the ability to proliferate in low-glucose environments and is inhibited by biguanides. The team’s results, recently published in Nature, show that defects in this pathway make cancer cells more sensitive to glucose limitation. These defects, as well as impaired glucose utilization, are potential biomarkers for predicting which tumors will be more sensitive to biguanides. This work was funded in part by the Koch Institute Frontier Research Program. more...

Genetic Road Map from the Jacks Laboratory Reveals Potential New Targets for SCLC

Koch Institute biologists, including KI Director and David H. Koch Professor of Biology, Tyler Jacks, and KI postdocs David McFadden and Thales Papagiannakopoulos, have collaborated with geneticists from the Broad Institute to perform the most comprehensive genetic analysis to date of lung cancer progression and growth using a genetically-defined mouse model of small cell lung cancer (SCLC). The findings, recently published in Cell, identify new drug targets and offer deeper insight into the evolution and spread of SCLC, which is strongly associated with heavy tobacco use.

The investigators took advantage of key features of the mouse model, including the absence of exposure to cigarette smoke that contributes to the very high number of mutations observed in human SCLC tumors. By isolating DNA from tumors at different times and analyzing the genetic alterations that occur, the team discovered that early on, tumors produce many copies of a gene called Mycl1, which is known to promote tumor cell proliferation. Over time, cancer cells go on to lose a gene called Pten, which regulates a critical pathway that controls growth and survival. The loss of Pten allows tumor cells to grow very rapidly.

By comparing the genomes of cells from the original lung tumors and from tumors that later appeared in other sites, the researchers also analyzed how the cancer migrated to remote sites beyond the lung. They found that multiple subsets of tumor cells from the lung moved to the lymph nodes, whereas usually only a single subset spread from the lymph nodes to the liver. Continued genetic analysis will help identify the specific mutations associated with both metastasis and drug resistance in these tumors.

The study was funded by the Ludwig Center for Molecular Oncology at MIT, the Howard Hughes Medical Institute, the National Human Genome Research Institute, a National Institutes of Health-National Cancer Institute Career Development Award, and a Hope Funds for Cancer Research Fellowship. more...

Behind the Music with Michael Hemann

KI faculty member Michael Hemann, the Eisen and Chang Career Development Associate Professor of Biology at MIT, is hitting all the right notes in his quest to develop better ways to deploy chemotherapy. The Hemann Laboratory uses innovative approaches to discover how tumors develop resistance to chemotherapeutics and to identify genetic markers that can predict the success or failure of cancer treatments. What many people don’t know about Ohio native Michael Hemann, however, is that he once dreamed of becoming a museum curator. As part of a new series featuring recently tenured professors, MIT News sat down with Hemann to discuss his career, his research, and his passion for music. An avid bass guitar player, Hemann compares his role as a principal investigator in the lab with that of the bass guitar locking in the way a band sounds. “It’s my job to keep things together and let the rest of them be virtuosos,” he says. His approach seems to be working—he and his colleagues have already begun developing new combination therapies to overcome drug resistance. And that just plain rocks! more...

Hynes Lab Identifies Extracellular Proteins that Help Tumors Metastasize

KI faculty member and Daniel K. Ludwig Professor for Cancer Research Richard Hynes and a group of colleagues led by KI postdoc Alexandra Naba have discovered that certain proteins in the extracellular matrix, the supportive scaffold that gives tissues their structure, help cancer cells escape their original locations to spread through the body. The researchers identified dozens of proteins that surround highly metastatic breast cancer tumors, but not less aggressive tumors, and found that four of those proteins are critical to metastasis. The findings, which appear in the journal eLife, could lead to new tests that predict which tumors are most likely to metastasize, and may also help to identify new therapeutic targets for metastatic tumors. “In principle, one could imagine interfering with some of these extracellular proteins and blocking metastasis in a patient. We’re a long way from that, but it’s not inconceivable,” says Hynes. The researchers are now looking for extracellular matrix proteins that are overexpressed in metastatic colon and pancreatic cancers, and are also studying the role of extracellular matrix proteins in tissues to which tumors often metastasize. more...

Belcher's Work Featured in The Economist

KI faculty member and recent MIT-Lemelson Award winner Angela Belcher was featured in the March 8th issue of The Economist. The profile provides an overview of Belcher’s career and her multidisciplinary and eclectic research work, which spans batteries, digital touch-screens, cleanup of industrial wastewater, and new cancer-seeking viruses to detect and potentially treat cancer at its early stage. Belcher’s trademark toolkit is behind this broad array of applications: using genetically engineered microorganisms to manufacture new materials and devices. Her work making biodegradable batteries from viruses was also featured this month in The New Scientist. “There are so many areas we would like to be involved in, but we can’t do them all,” Belcher says. more...

Hammond Joins National “We The Geeks” Online STEM Discussion in Honor of Black History Month

Last February, KI faculty member and David H. Koch Professor in Engineering Paula Hammond participated in a live White House Google+ Hangout entitled “We the Geeks: Celebrating Black History Month.” The online conversation, hosted by the Office of Science and Technology Policy, brought together seven African American STEM innovators and educators to talk about how this country’s STEM workforce can be broadened, diversified, and strengthened.

Hammond described her childhood excitement for science, inspired by her high school chemistry class. “The magic of chemistry got me excited…that you can have something that never existed before by putting two things that are very different together,” she said. She also discussed her current research on nanomaterials—materials the size of one strand of hair split 10,000 times, she explained— including her work on nanoparticles that can deliver cancer treatments specifically to target tumor cells while avoiding healthy ones. more...

Senior Dylan Soukup Fights Cancer on Two Fronts

MIT senior and Koch Institute UROP Dylan Soukup was recently profiled by MIT News for his deep commitment to medicine, cancer research, and the MIT community.

Cancer has had a tremendous effect on Dylan Soukup's life; at the age of five months he was diagnosed with neuroblastoma. Soukup was cured by the time he was five, and although today he doesn’t remember having had cancer, the experience has had a lasting impact. One of the factors that drew him to MIT was the Koch Institute. As a sophomore, he began conducting research in the Jacks Laboratory. In addition to his work at the KI, Soukup is co-director of the MIT chapter of Camp Kesem, a summer program for children who have a parent with cancer. He also leads the MIT EMS team, providing emergency services to the MIT campus. It was in this role that Soukup met MIT Police Officer Sean Collier. Soukup's EMS ambulance was the first on the scene of the shooting in April 2013.

Soukup, who plans to become a surgeon, believes this tragic event, along with his involvement in the cancer research community at MIT, has fortified his ever-growing dedication to a career in medicine. “Working on the MIT ambulance and responding to the shooting of Officer Collier showed me the power of this community to support and rebuild,” he says. “Above all else, the Koch Institute, in showing me that the greatest minds are working together to approach cancer from every angle, has given me hope that someday my friends, my family, and my campers will be spared the devastation of cancer.” On February 25, the MIT EMS team that Soukup leads received the inaugural award of the Collier Medal for model service to the MIT community. The medal is a tribute to Officer Collier's commitment to serving MIT and a lasting reminder of his dedication. more...

Bhatia’s Paper-based Urine Test for Cancer, a Game Changer

MIT engineers led by KI faculty member Sangeeta Bhatia have developed a simple, cheap, paper-strip urine test that can reveal the presence of cancer within minutes. The paper-based diagnostic, described in the Proceedings of the National Academy of Sciences, can be performed on unprocessed samples without specialized equipment and can be modified to detect different types or stages of disease. This point-of-care, image-free test is a big leap forward in bringing cancer detection to settings with little medical infrastructure. In countries where more advanced diagnostics are available, it could provide an inexpensive alternative to imaging. The technology relies on nanoparticles that interact with tumor proteins called proteases, each of which releases hundreds of biomarkers detectable in a patient’s urine. In the original version of the technology, these biomarkers were detected using a highly specialized instrument called a mass spectrometer. Now, applying the same technology used in pregnancy tests, the researchers have adapted the particles so they can be analyzed on paper. The Bhatia Laboratory recently won a grant from MIT’s Deshpande Center for Technological Innovation to develop a business plan for a startup to commercialize the technology and perform clinical trials to bring this diagnostic to patients. The research has been profiled in media outlets including The Boston Globe, The Huffington Post, Boston Magazine, The Times of India, and The Indian Express, and was funded by a National Science Foundation Graduate Research Fellowship, a Mazumdar-Shaw International Oncology Fellowship, the Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Burroughs Wellcome Fund, the National Cancer Institute, and the Howard Hughes Medical Institute. more...

Irvine’s Albumin-targeted Vaccines Hitch a Ride to the Lymph Nodes to Boost Immunity

Vaccines made of small fragments of proteins produced by a disease-causing virus or bacterium are, in many cases, safer than those composed of inactivated versions of a virus. However, these peptide antigen vaccines often fail to provoke a strong enough immune response. In a paper published in Nature, KI faculty member Darrell Irvine and his team describe the development of a new way to deliver such vaccines directly to the immune cell depots, the lymph nodes. Their strategy takes advantage of the function of a protein in the bloodstream known as albumin, which is a transporter of fatty acids. Inspired by an existing procedure for targeting imaging dyes to the lymph nodes, the team’s vaccines are designed to bind to albumin, triggering the immune cells to capture the albumin and take it to the lymph nodes. In animal tests, these "hitchhiking" vaccines provoked immune responses up to 30 times stronger than those generated by the peptide antigens alone. This approach could be especially useful for delivering HIV vaccines and for stimulating the body’s immune system to attack tumors. more...

Sharp Calls for Increased Links between Discovery, Innovation, and Entrepreneurship

KI faculty member and Institute Professor Phillip A. Sharp, the AAAS President, echoed the KI’s emphasis on interdisciplinary research in his opening President’s Address at this year’s AAAS meeting in Chicago. “If discovery is to come to the aid of our great global challenges of climate change, poverty and disease,” Sharp said, “we have no choice but to become much better at linking discovery, innovation, and entrepreneurship.” Sharp himself is both scientist and entrepreneur; he has co-founded two companies, Biogen (now Biogen Idec) and Alnylam Pharmaceuticals, which build on his research developing therapeutic methods to switch genes on and off through RNA interference (RNAi). Sharp encouraged attendees to consider and foster links between biological, physical, computational and engineering sciences, which form “the blueprint for future innovation.” more...

Anderson and Langer’s Nature-mimicking Nanoparticles

A new study published in the Proceedings of the National Academy of Sciences and featured in The Boston Globe describes the work of KI faculty members Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering, and Robert Langer, the David H. Koch Institute Professor, in designing new nanoparticles that efficiently and selectively deliver snippets of genetic material that turn off disease-causing genes (an approach known as RNA interference) in the liver. These nanoparticles, which are inspired by tiny particles that carry cholesterol through the body, silence target genes in the liver more efficiently than any previous delivery system. The technology has already been licensed for commercial development and holds great promise to treat cancer by selectively blocking mutated cancer-causing genes. more...

Bridge Project Team Sets New Standard for In Vivo Discovery of New Targets for Cancer Immunotherapy

The recent release of promising clinical data from cancer immunotherapies has generated considerable optimism in the cancer research community. Recent work has shown that targeting inhibitory receptors on T cells can result in clinical benefits in patients with advanced cancers. However, the regulatory switches of the immune function in immunosuppressive tumors are not well understood. A multidisciplinary group of investigators, including the Bridge Project-funded team composed of KI faculty members Hidde Ploegh and Chris Love, and Dana-Farber Cancer Institute's Kai Wucherpfennig, used short hairpin RNA (shRNA) screening to identify genes that modify the action of tumor-infiltrating CD8+ T cells in mice bearing melanomas. The group identified the regulatory phosphatase Ppp2r2d as a target and showed that knocking down this gene in T cells enabled their accumulation in tumors and delayed tumor growth. This groundbreaking study, published in Nature, provides a new approach to further dissecting the function of immune cells in vivo and identifying new targets for cancer therapy. The work was partially supported by the Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center designed to bring bioengineering, advanced cancer science, and clinical oncology together to solve challenging problems in cancer research and care. more...

Combining Biology and Engineering to Improve Drug Discovery

A recent MIT News article highlights how KI faculty member Linda Griffith is fusing systems biology and tissue engineering to accelerate drug discovery and better understand how cells metabolize drugs—and why some chemotherapies fail in treating cancers. “I myself had triple-negative breast cancer, and I came to appreciate how hard it is to develop new cancer drugs to treat patients,” she says. Griffith is using a 3D “bioreactor” model of the human liver that she previously developed to study what causes metastatic triple-negative breast cancer cells to die or to proliferate. She also leads one of the research efforts under the Microphysiological Systems or “body on a chip” research program at MIT, a project funded by DARPA that aims to replicate human physiological systems on a single platform to look at how they crosstalk. As the Director of the MIT Center for Gynepathology Research, Griffith has collaborated with KI faculty member Douglas Lauffenburger and surgeon Keith Isaacson of Newton-Wellesley Hospital on a systems biology approach to study inflammation in endometriosis. The latter work was recently featured in The Boston Globe and The New Yorker. more...

Hemann & Chen Combine Forces against Resistant Tumors

KI faculty members Michael Hemann, the Eisen and Chang Career Development Associate Professor of Biology, and Jianzhu Chen, the Ivan R. Cottrell Professor of Immunology, have discovered a new treatment for drug-resistant tumors using a combination of existing drugs. In a study published in Cell, the KI team showed that the simultaneous administration of an antibody drug called alemtuzumab (which is FDA-approved for some cancers and in clinical trials for some forms of lymphoma) and cyclophosphamide (a drug that is often given to cancer patients) makes tumor cells more vulnerable to the antibody treatment. Cyclophosphamide stimulates the immune response in bone marrow, eliminating the reservoir of cancer cells that can produce new tumors after treatment and avoiding tumor recurrence. The researchers also reported good results by combining cyclophosphamide with rituximab, another antibody drug used to treat lymphoma and leukemia. They now plan to test cyclophosphamide with other types of antibody drugs for breast and prostate tumors. This research was funded by the MIT Ludwig Center for Molecular Oncology, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the Singapore-MIT Alliance for Research and Technology, the German Research Foundation, and the National Cancer Institute. First author and former KI postdoc Christian Pallasch plans to begin testing the alemtuzumab-cyclophosphamide treatment in lymphoma patients. more...

KI Member Angelika Amon Receives Genetics Society of America Medal

The KI congratulates faculty member Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, on receiving the 2014 Genetics Society of America Medal. The medal, established in 1981, honors elegant and highly meaningful contributions to modern genetics in the past 15 years. Amon is being recognized by the wider genetics community for her contributions to uncovering key principles of the cell cycle and cell division. more...

Manalis Measures Miniscule Masses

KI faculty member Scott Manalis has created a new sensor that can measure weights at the attogram scale, or one millionth of a trillionth of a gram. This work appears in the Proceedings of the National Academy of Sciences and also involves KI faculty members Angela Belcher and Sangeeta Bhatia.

Manalis developed an earlier version of the device, called a suspended microchannel resonator. It measures the mass of living cells as they flow through a narrow channel etched in a tiny silicon cantilever that behaves like a diving board. His team subsequently used it to track the growth and other physical properties of cancer cells such as density, stiffness, and friction. Now, by shrinking the entire system, the researchers have improved its resolution 30-fold. This allows them to weigh small viruses, extracellular vesicles, and nanoparticles to better understand their composition and function. The Manalis team plans to use the new suspended nanochannel resonator for high-precision detection and monitoring of cancer progression and treatment response. For example, glioblastoma tumors secrete large quantities of biological vesicles known as exosomes, and the investigators are using their new device to detect exosomes in blood samples of patients with this type of brain cancer. more...

Ludwig Center Receives $90M for Cancer Research Endowment at MIT

The Ludwig Center at MIT is one of six centers to receive a total of $540 million in new financial support from Ludwig Cancer Research on behalf of its founder, the late American shipping magnate Daniel K. Ludwig. The new gift adds to the endowments established in 2006 to create the Ludwig Centers at each institution, and is one of the largest in MIT's history.

Headed by Koch Institute member and Daniel K. Ludwig Professor for Cancer Research at MIT Robert Weinberg, the Ludwig Center for Molecular Oncology at MIT is focused on understanding and disrupting the metastatic spread of cancer. Ludwig funds currently support six faculty members, all of whom are located at the KI, along with several fellowships for students and postdoctoral researchers.

“We are extremely grateful to receive this gift in support of cancer research,” said Tyler Jacks, a Daniel K. Ludwig Scholar at the Ludwig Center at MIT and director of the Koch Institute, “and we are committed to using these funds to make a meaningful impact on the important problem of metastasis." The Ludwig gift adds considerable strength and long-term sustainability to MIT's interdisciplinary approach to cancer research, and has been profiled in media outlets including MIT News, The Boston Globe, The Wall Street Journal, and USA Today. more...

Koch Institute for Integrative Cancer Research
Massachusetts Institute of Technology
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News Archive: 2014

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