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Wednesday, March 16th, 2016
| Time |
Event |
| 12:05a |
U.S. News gives top rankings to MIT graduate programs in engineering, business MIT’s graduate program in engineering has once more placed at the top of U.S. News & World Report’s annual list of the nation’s graduate programs. The Institute has held the No. 1 spot since 1990, when the magazine first ranked such programs.
The MIT Sloan School of Management also placed highly, coming in as the No. 5 graduate program in business for the third year in a row.
MIT’s graduate program in engineering was the only one to earn an overall score of 100. It was followed by Stanford University (87), the University of California at Berkeley (81), and Caltech (75).
The U.S. News list also ranked individual engineering disciplines across universities; top honors went to MIT for aerospace engineering, chemical engineering, computer engineering, electrical/electronics/communications engineering (tied with Stanford and Berkeley), materials engineering, and mechanical engineering (tied with Stanford). MIT also received the No. 2 ranking in nuclear engineering and biomedical engineering (tied with Georgia Tech).
In the rankings of graduate programs in business, MIT Sloan ranked fifth, behind programs at Harvard University, Stanford, the University of Chicago, and the University of Pennsylvania.
MIT Sloan’s graduate programs in information systems, production/operations, and supply chain/logistics were again ranked first this year; the Institute’s graduate program in entrepreneurship was also highly ranked, at No. 3 (tied with Harvard).
U.S. News does not issue annual rankings for all doctoral programs, but revisits many every few years. In the magazine’s 2014 evaluation of PhD programs in the sciences, five MIT programs earned a No. 1 ranking: biological sciences (tied with Harvard and Stanford); chemistry (tied with Caltech and Berkeley, and with a No. 1 ranking in the specialty of inorganic chemistry); computer science (tied with Carnegie Mellon University, Stanford, and Berkeley); mathematics (tied with Princeton University, and with a No. 1 ranking in the specialty of discrete mathematics and combinations); and physics. In a 2013 evaluation of graduate programs in economics, MIT tied for first place with Harvard, Princeton, and Chicago, with a No. 1 ranking in the specialty of econometrics.
U.S. News bases its rankings of graduate schools of engineering and business on two types of data: reputational surveys of deans and other academic officials, and statistical indicators that measure the quality of a school’s faculty, research, and students. The magazine’s less-frequent rankings of programs in the sciences, social sciences, and humanities are based solely on reputational surveys. | | 12:05a |
Why some tumors withstand treatment New cancer drugs allow doctors to tailor treatment based on the genetic profile of a patient’s tumor. However, these drugs don’t work at all in some patients, and they lose their effectiveness in others.
A new study from MIT and Massachusetts General Hospital reveals why a certain class of these drugs, known as kinase inhibitors, doesn’t always halt tumor growth. The researchers found that while kinase inhibitors successfully shut down their targets, they also provoke cells to turn on a backup system that can take over for the one knocked out by the drug.
The team also showed that disrupting both systems with a combination of drugs yields much better results, in a study of mice.
“We’ve discovered a previously unappreciated mechanism involved in resistance to targeted therapeutics,” says Douglas Lauffenburger, the Ford Professor of Bioengineering and head of MIT’s Department of Biological Engineering. “Its presence appears to be associated with poor response to some kinase inhibitors in clinical patients. And we’ve demonstrated that in mice adding a drug against this resistance mechanism allows the original targeted drug to work when otherwise it wouldn’t.”
Lauffenburger, who is also an affiliate member of MIT’s Koch Institute for Integrative Cancer Research, is the senior author of the study, which appears in the March 16 online edition of Cancer Discovery. The lead authors are Miles Miller, a former MIT graduate student who is now a postdoc at Harvard Medical School, and Madeleine Oudin, a Koch Institute postdoc.
Bypass system
Kinase inhibitors, frequently used against breast, ovarian, and other cancers, work by disrupting cell signaling pathways that stimulate cells to grow, proliferate, or become invasive. Doctors usually prescribe them based on whether a patient’s tumor is overexpressing a cancer-driving protein such as epithelial growth factor receptor (EGFR).
However, these drugs can fail even in tumors where they should work. About half of these failures are caused by genetic mutations that allow cancer cells to evade the drug’s actions, but the rest are unexplained, Lauffenburger says.
Based on their previous studies of endometriosis (when uterine tissue grows into surrounding organs), Lauffenburger and his colleagues suspected there could be a backup pathway helping cancer cells to sidestep the effects of kinase inhibitors. In those studies, the researchers found that invasive endometrial cells become “addicted” to a certain growth signal, and that this pathway actually shuts off other growth pathways. Drugs that shut down the primary pathway can have the unintended effect of activating those backup systems.
The MIT team wondered if the same thing might be happening in cancer cells. They focused on melanoma and triple-negative breast cancer, two very aggressive forms of cancer that are often driven by EGFR ligands (molecules that activate the receptor), which help the cancer cells to become motile and invasive.
They found that when EGFR ligands bind to receptors on the cancer cell surface, they not only trigger a cascade of cellular reactions that promotes invasiveness but also activate a positive feedback loop: Enzymes called proteases release EGFR ligands from the cell surface so they can bind to even more receptors, strengthening the pro-invasion signal.
The researchers found that those proteases also chop off receptors that initiate other pro-invasion pathways. Essentially, the cancer cells become addicted to the EGFR-driven pathway and shut off competing pathways because they don’t need them, Lauffenburger says.
“The cells have the capability for other inputs, but if they’re already signaling through one, they’re perfectly happy to shut down the rest,” he says.
Consequently, when doctors give a kinase inhibitor that shuts off the EGFR pathway, it also shuts off the proteases, allowing the backup pathways, which are no longer being suppressed, to take over.
More accurate predictions
The researchers also showed that these cleaved receptor proteins can be detected in blood samples from patients, and that the protein levels correlate with how well EGFR inhibitors work for individual patients.
High levels of cleaved proteins mean that there is a lot of potential for the backup system to kick in, and kinase inhibitors will not be effective. However, if these protein levels are low, that suggests the backup system is not very strong in that patient’s tumor.
“The discovery seems to identify those patients who will go on to receive long-term clinical benefit versus those whose tumors will quickly adapt and circumvent treatment, by virtue of a blood-based test that can be performed at baseline or within days of initiating treatment,” says Keith Flaherty, an author of the paper and director of developmental therapeutics at the MGH Cancer Center, who hopes to begin performing this kind of test in patients.
The study also suggests that patients whose tumors have a strong backup system could benefit from receiving an EGFR inhibitor plus a drug that shuts down the secondary pathway. One candidate is a type of drug known as an AXL inhibitor, which is now in clinical trials. In mouse studies, the MIT team found that treating tumors with that combination of drugs was much more effective than giving either one alone.
“Not only can the activation of this novel drug resistance mechanism be identified in patients by measuring (blood) serum receptor levels, but it is therapeutically tractable by combined targeting of cell surface receptors and intracellular signaling molecules. This important study provides novel mechanisms, new biomarkers, and the potential for rapid implementation to improving patient outcomes,” says Gordon Mills, a professor of medicine and immunology at the University of Texas MD Anderson Cancer Center, who was not involved in the research.
Other MIT authors include Frank Gertler, a professor of biology and member of the Koch Institute, Linda Griffith, a professor of biological engineering and mechanical engineering and affiliate member of the Koch Institute, graduate student Stephanie Wang, research scientist Aaron Meyer, and technical associate Jenny Tadros.
The research was funded by the National Cancer Institute Centers for Cancer Systems Biology program. | | 9:08a |
Administration addresses student recommendations In December 2015, student leaders from the Black Students’ Union (BSU) and the Black Graduate Student Association (BGSA) presented MIT’s senior administration with recommendations for making the Institute a more welcoming and inclusive place for all members of its community. The Academic Council, chaired by President L. Rafael Reif, is partnering with the students to consider all the recommendations and move forward with steps to address them.
Those changes that can be implemented soon will be in place within a matter of months; others will take more time. A dedicated Academic Council working group, convened by Vice President Kirk Kolenbrander and consisting of students, faculty, and senior officers, will share a public progress report around the time of spring break.
The report will outline the actions being taken in the shorter term, including enhancements to orientation for incoming students and the recruitment of a specialized mental health counselor, according to Kolenbrander. For the longer-term goals, the working group will describe its plan for moving forward.
The process “has been very collaborative, very productive, and very strategic in terms of thinking of cooperative ways that we can best meet the needs of students,” says DiOnetta Jones Crayton, associate dean for undergraduate education and director of the Office of Minority Education. Crayton is a member of a staff group Kolenbrander convened in the fall to advance the Institute’s partnership with a number of student groups working on diversity and inclusion issues.
“The opportunity to collaboratively work toward creative solutions feels more like a group effort than a negotiation. I am proud that MIT can put a group like this together to tackle systematic issues swiftly but delicately,” says junior Rasheed Auguste, co-chair of the BSU and a participant in the Academic Council working group.
Both sets of student recommendations, one focusing on the undergraduate experience, the other on graduate students, originated with a November conversation between the student leaders and President Reif, who reached out to see how the students were feeling in the wake of racially charged incidents taking place at the time on other campuses.
The administration has also encouraged other groups at MIT to make their own suggestions and has received “well over 80 different recommendations,” according to Kolenbrander. All of the suggestions have several “deep themes” in common, he says, and to keep the task manageable, the working group is focusing now on the recommendations from the BSU and BGSA while also laying a path for considering all of the others. “All constituencies have a voice and need to be engaged,” Kolenbrander says.
One of the BSU recommendations, namely to reaffirm MIT’s commitment to accessibility and affordability by increasing financial aid, has already been addressed: MIT announced on March 4 that the Institute’s undergraduate financial aid budget for 2016-17 will increase by 10.4 percent, a change that will result in more generous MIT scholarships for nearly all students who receive financial aid.
Other advances are very close to finalization. Undergraduate orientation in 2016 will include small-group conversations on diversity, facilitated by trained faculty and staff. And discussions are underway to make diversity training a component of the activities for incoming graduate students.
Leadership at MIT Medical is working to recruit a specialist with expertise in race-based traumatic stress and other psychological issues affecting under-represented minorities on campus.
An analysis is nearing completion that will capture data on undergraduate retention rate and flow within departments. This will be accompanied by a plan for data release practices, in order to ensure student privacy. Additionally, Institutional Research is working with the students on questions to pilot in the upcoming senior survey.
Responding to the students’ call in December, every member of Academic Council has agreed to participate in unconscious-bias training this semester. Additionally, this week Institute Community and Equity Officer Ed Bertschinger is hosting the first in a series of unconscious bias trainings that all faculty, students, and staff are invited to take part in.
Responses to other recommendations, including those that require action by every department, are still in progress. Kolenbrander is confident that the ultimate outcomes will reflect the student recommendations in spirit, even if the steps taken by each department are not identical. “We can have conversations that lead us toward an articulation of our shared values, and we can get everyone to sign off on that. Those conversations are going on now,” Kolenbrander says. | | 2:00p |
“Lost” memories can be found In the early stages of Alzheimer’s disease, patients are often unable to remember recent experiences. However, a new study from MIT suggests that those memories are still stored in the brain — they just can’t be easily accessed.
The MIT neuroscientists report in Nature that mice in the early stages of Alzheimer’s can form new memories just as well as normal mice but cannot recall them a few days later.
Furthermore, the researchers were able to artificially stimulate those memories using a technique known as optogenetics, suggesting that those memories can still be retrieved with a little help. Although optogenetics cannot currently be used in humans, the findings raise the possibility of developing future treatments that might reverse some of the memory loss seen in early-stage Alzheimer’s, the researchers say.
“The important point is, this a proof of concept. That is, even if a memory seems to be gone, it is still there. It’s a matter of how to retrieve it,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory.
Tonegawa is the senior author of the study, which appears in the March 16 online edition of Nature. Dheeraj Roy, an MIT graduate student, is the paper’s lead author.
Lost memories
In recent years, Tonegawa’s lab has identified cells in the brain’s hippocampus that store specific memories. The researchers have also shown that they can manipulate these memory traces, or engrams, to plant false memories, activate existing memories, or alter a memory’s emotional associations.
Last year, Tonegawa, Roy, and colleagues found that mice with retrograde amnesia, which follows traumatic injury or stress, had impaired memory recall but could still form new memories. That led the team to wonder whether this might also be true for the memory loss seen in the early stages of Alzheimer’s disease, which occurs before characteristic amyloid plaques appear in patients’ brains.
To investigate that possibility, the researchers studied two different strains of mice genetically engineered to develop Alzheimer’s symptoms, plus a group of healthy mice.
All of these mice, when exposed to a chamber where they received a foot shock, showed fear when placed in the same chamber an hour later. However, when placed in the chamber again several days later, only the normal mice still showed fear. The Alzheimer’s mice did not appear to remember the foot shock.
“Short-term memory seems to be normal, on the order of hours. But for long-term memory, these early Alzheimer’s mice seem to be impaired,” Roy says.
“An access problem”
The researchers then showed that while the mice cannot recall their experiences when prompted by natural cues, those memories are still there.
To demonstrate this, they first tagged the engram cells associated with the fearful experience with a light-sensitive protein called channelrhodopsin, using a technique they developed in 2012. Whenever these tagged engram cells are activated by light, normal mice recall the memory encoded by that group of cells. Likewise, when the researchers placed the Alzheimer’s mice in a chamber they had never seen before and shined light on the engram cells encoding the fearful experience, the mice immediately showed fear.
“Directly activating the cells that we believe are holding the memory gets them to retrieve it,” Roy says. “This suggests that it is indeed an access problem to the information, not that they’re unable to learn or store this memory.”
The researchers also showed that the engram cells of Alzheimer’s mice had fewer dendritic spines, which are small buds that allow neurons to receive incoming signals from other neurons.
Normally, when a new memory is generated, the engram cells corresponding to that memory grow new dendritic spines, but this did not happen in the Alzheimer’s mice. This suggests that the engram cells are not receiving sensory input from another part of the brain called the entorhinal cortex. The natural cue that should reactivate the memory — being in the chamber again — has no effect because the sensory information doesn’t get into the engram cells.
“If we want to recall a memory, the memory-holding cells have to be reactivated by the correct cue. If the spine density does not go up during learning process, then later, if you give a natural recall cue, it may not be able to reach the nucleus of the engram cells,” Tonegawa says.
“This is a remarkable study providing the first proof that the earliest memory deficit in Alzheimer’s involves retrieval of consolidated information,” says Rudolph Tanzi, a professor of neurology at Harvard Medical School, who was not involved in the research. “As a result, the implications for treatment of memory deficits Alzheimer’s disease based on strengthening synapses are extremely exciting.”
Long-term connection
The researchers were also able to induce a longer-term reactivation of the “lost” memories by stimulating new connections between the entorhinal cortex and the hippocampus.
To achieve this, they used light to optogenetically stimulate entorhinal cortex cells that feed into the hippocampal engram cells encoding the fearful memory. After three hours of this treatment, the researchers waited a week and tested the mice again. This time, the mice could retrieve the memory on their own when placed in the original chamber, and they had many more dendritic spines on their engram cells.
However, this approach does not work if too large a section of the entorhinal cortex is stimulated, suggesting that any potential treatments for human patients would have to be very targeted. Optogenetics is very precise but too invasive to use in humans, and existing methods for deep brain stimulation — a form of electrical stimulation sometimes used to treat Parkinson’s and other diseases — affect too much of the brain.
“It’s possible that in the future some technology will be developed to activate or inactivate cells deep inside the brain, like the hippocampus or entorhinal cortex, with more precision,” Tonegawa says. “Basic research as conducted in this study provides information on cell populations to be targeted, which is critical for future treatments and technologies.” |
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