News Archive: 2014

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 scientific advances and 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...

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 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 drugsand 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...