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    The tenured engineers of 2023

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    In 2023, MIT granted tenure to nine faculty members across the School of Engineering. This year’s tenured engineers hold appointments in the departments of Biological Engineering, Civil and Environmental Engineering, Electrical Engineering and Computer Science (which reports jointly to the School of Engineering and MIT Schwarzman College of Computing), Materials Science and Engineering, and Mechanical Engineering, as well as the Institute for Medical Engineering and Science (IMES).

    “I am truly inspired by this remarkable group of talented faculty members,” says Anantha Chandrakasan, dean of the School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “The work they are doing, both in the lab and in the classroom, has made a tremendous impact at MIT and in the wider world. Their important research has applications in a diverse range of fields and industries. I am thrilled to congratulate them on the milestone of receiving tenure.”

    This year’s newly tenured engineering faculty include:

    Michael Birnbaum, Class of 1956 Career Development Professor, associate professor of biological engineering, and faculty member at the Koch Institute for Integrative Cancer Research at MIT, works on understanding and manipulating immune recognition in cancer and infections. By using a variety of techniques to study the antigen recognition of T cells, he and his team aim to develop the next generation of immunotherapies.  
    Tamara Broderick, associate professor of electrical engineering and computer science and member of the MIT Laboratory for Information and Decision Systems (LIDS) and the MIT Institute for Data, Systems, and Society (IDSS), works to provide fast and reliable quantification of uncertainty and robustness in modern data analysis procedures. Broderick and her research group develop data analysis tools with applications in fields, including genetics, economics, and assistive technology. 
    Tal Cohen, associate professor of civil and environmental engineering and mechanical engineering, uses nonlinear solid mechanics to understand how materials behave under extreme conditions. By studying material instabilities, extreme dynamic loading conditions, growth, and chemical coupling, Cohen and her team combine theoretical models and experiments to shape our understanding of the observed phenomena and apply those insights in the design and characterization of material systems. 
    Betar Gallant, Class of 1922 Career Development Professor and associate professor of mechanical engineering, develops advanced materials and chemistries for next-generation lithium-ion and lithium primary batteries and electrochemical carbon dioxide mitigation technologies. Her group’s work could lead to higher-energy and more sustainable batteries for electric vehicles, longer-lasting implantable medical devices, and new methods of carbon capture and conversion. 
    Rafael Jaramillo, Thomas Lord Career Development Professor and associate professor of materials science and engineering, studies the synthesis, properties, and applications of electronic materials, particularly chalcogenide compound semiconductors. His work has applications in microelectronics, integrated photonics, telecommunications, and photovoltaics. 
    Benedetto Marelli, associate professor of civil and environmental engineering, conducts research on the synthesis, assembly, and nanomanufacturing of structural biopolymers. He and his research team develop biomaterials for applications in agriculture, food security, and food safety. 
    Ellen Roche, Latham Family Career Development Professor, an associate professor of mechanical engineering, and a core faculty of IMES, designs and develops implantable, biomimetic therapeutic devices and soft robotics that mechanically assist and repair tissue, deliver therapies, and enable enhanced preclinical testing. Her devices have a wide range of applications in human health, including cardiovascular and respiratory disease. 
    Serguei Saavedra, associate professor of civil and environmental engineering, uses systems thinking, synthesis, and mathematical modeling to study the persistence of ecological systems under changing environments. His theoretical research is used to develop hypotheses and corroborate predictions of how ecological systems respond to climate change. 
    Justin Solomon, associate professor of electrical engineering and computer science and member of the MIT Computer Science and Artificial Intelligence Laboratory and MIT Center for Computational Science and Engineering, works at the intersection of geometry, large-scale optimization, computer graphics, and machine learning. His research has diverse applications in machine learning, computer graphics, and geometric data processing.  More

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      Making sense of cell fate

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      Despite the proliferation of novel therapies such as immunotherapy or targeted therapies, radiation and chemotherapy remain the frontline treatment for cancer patients. About half of all patients still receive radiation and 60-80 percent receive chemotherapy.

      Both radiation and chemotherapy work by damaging DNA, taking advantage of a vulnerability specific to cancer cells. Healthy cells are more likely to survive radiation and chemotherapy since their mechanisms for identifying and repairing DNA damage are intact. In cancer cells, these repair mechanisms are compromised by mutations. When cancer cells cannot adequately respond to the DNA damage caused by radiation and chemotherapy, ideally, they undergo apoptosis or die by other means.

      However, there is another fate for cells after DNA damage: senescence — a state where cells survive, but stop dividing. Senescent cells’ DNA has not been damaged enough to induce apoptosis but is too damaged to support cell division. While senescent cancer cells themselves are unable to proliferate and spread, they are bad actors in the fight against cancer because they seem to enable other cancer cells to develop more aggressively. Although a cancer cell’s fate is not apparent until a few days after treatment, the decision to survive, die, or enter senescence is made much earlier. But, precisely when and how that decision is made has not been well understood.

      In an open-access study of ovarian and osteosarcoma cancer cells appearing July 19 in Cell Systems, MIT researchers show that cell signaling proteins commonly associated with cell proliferation and apoptosis instead commit cancer cells to senescence within 12 hours of treatment with low doses of certain kinds of chemotherapy.

      “When it comes to treating cancer, this study underscores that it’s important not to think too linearly about cell signaling,” says Michael Yaffe, who is a David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. “If you assume that a particular treatment will always affect cancer cell signaling in the same way — you may be setting yourself up for many surprises, and treating cancers with the wrong combination of drugs.”

      Using a combination of experiments with cancer cells and computational modeling, the team investigated the cell signaling mechanisms that prompt cancer cells to enter senescence after treatment with a commonly used anti-cancer agent. Their efforts singled out two protein kinases and a component of the AP-1 transcription factor complex as highly associated with the induction of senescence after DNA damage, despite the well-established roles for all of these molecules in promoting cell proliferation in cancer.

      The researchers treated cancer cells with low and high doses of doxorubicin, a chemotherapy that interferes with the function with topoisomerase II, an enzyme that breaks and then repairs DNA strands during replication to fix tangles and other topological problems.

      By measuring the effects of DNA damage on single cells at several time points ranging from six hours to four days after the initial exposure, the team created two datasets. In one dataset, the researchers tracked cell fate over time. For the second set, researchers measured relative cell signaling activity levels across a variety of proteins associated with responses to DNA damage or cellular stress, determination of cell fate, and progress through cell growth and division.

      The two datasets were used to build a computational model that identifies correlations between time, dosage, signal, and cell fate. The model identified the activities of the MAP kinases Erk and JNK, and the transcription factor c-Jun as key components of the AP-1 protein likewise understood to involved in the induction of senescence. The researchers then validated these computational findings by showing that inhibition of JNK and Erk after DNA damage successfully prevented cells from entering senescence.

      The researchers leveraged JNK and Erk inhibition to pinpoint exactly when cells made the decision to enter senescence. Surprisingly, they found that the decision to enter senescence was made within 12 hours of DNA damage, even though it took days to actually see the senescent cells accumulate. The team also found that with the passage of more time, these MAP kinases took on a different function: promoting the secretion of proinflammatory proteins called cytokines that are responsible for making other cancer cells proliferate and develop resistance to chemotherapy.

      “Proteins like cytokines encourage ‘bad behavior’ in neighboring tumor cells that lead to more aggressive cancer progression,” says Tatiana Netterfield, a graduate student in the Yaffe lab and the lead author of the study. “Because of this, it is thought that senescent cells that stay near the tumor for long periods of time are detrimental to treating cancer.”

      This study’s findings apply to cancer cells treated with a commonly used type of chemotherapy that stalls DNA replication after repair. But more broadly, the study emphasizes that “when treating cancer, it’s extremely important to understand the molecular characteristics of cancer cells and the contextual factors such as time and dosing that determine cell fate,” explains Netterfield.

      The study, however, has more immediate implications for treatments that are already in use. One class of Erk inhibitors, MEK inhibitors, are used in the clinic with the expectation that they will curb cancer growth.

      “We must be cautious about administering MEK inhibitors together with chemotherapies,” says Yaffe. “The combination may have the unintended effect of driving cells into proliferation, rather than senescence.”

      In future work, the team will perform studies to understand how and why individual cells choose to proliferate instead of enter senescence. Additionally, the team is employing next-generation sequencing to understand which genes c-Jun is regulating in order to push cells toward senescence.

      This study was funded, in part, by the Charles and Marjorie Holloway Foundation and the MIT Center for Precision Cancer Medicine. More

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      Novo Nordisk to support MIT postdocs working at the intersection of AI and life sciences

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      MIT’s School of Engineering and global health care company Novo Nordisk has announced the launch of a multi-year program to support postdoctoral fellows conducting research at the intersection of artificial intelligence and data science with life sciences. The MIT-Novo Nordisk Artificial Intelligence Postdoctoral Fellows Program will welcome its first cohort of up to 10 postdocs for a two-year term this fall. The program will provide up to $10 million for an annual cohort of up to 10 postdoc for two-year terms.

      “The research being conducted at the intersection of AI and life sciences has the potential to transform health care as we know it,” says Anantha Chandrakasan, dean of the School of Engineering and Vannevar Bush Professor of Electrical Engineering and Computer Science. “I am thrilled that the MIT-Novo Nordisk Program will support early-career researchers who work in this space.”

      The launch of the MIT-Novo Nordisk Program coincides with the 100th anniversary celebration of Novo Nordisk. The company was founded in 1923 and treated its first patients with insulin, which had recently been discovered in March of that year.

      “The use of AI in the health care industry presents a massive opportunity to improve the lives of people living with chronic diseases,” says Thomas Senderovitz, senior vice president for data science at Novo Nordisk. “Novo Nordisk is committed to the development of new, innovative solutions, and MIT hosts some of the most outstanding researchers in the field. We are therefore excited to support postdocs working on the cutting edge of AI and life sciences.”

      The MIT-Novo Nordisk Program will support postdocs advancing the use of AI in life science and health. Postdocs will join an annual cohort that participates in frequent events and gatherings. The cohort will meet regularly to exchange ideas about their work and discuss ways to amplify their impact.

      “We are excited to welcome postdocs working on AI, data science, health, and life sciences — research areas of strategic importance across MIT,” adds Chandrakasan.

      A central focus of the program will be offering postdocs professional development and mentorship opportunities. Fellows will be invited to entrepreneurship-focused workshops that enable them to learn from company founders, venture capitalists, and other entrepreneurial leaders. Fellows will also have the opportunity to receive mentorship from experts in life sciences and data science.

      “MIT is always exploring opportunities to innovate and enhance the postdoctoral experience,” adds MIT Provost Cynthia Barnhart. “The MIT-Novo Nordisk Program has been thoughtfully designed to introduce fellows to a wealth of experiences, skill sets, and perspectives that support their professional growth while prioritizing a sense of community with their cohort.”

      Angela Belcher, head of the Department of Biological Engineering, the James Mason Crafts Professor of Biological Engineering and Materials Science, and member of the Koch Institute for Integrative Cancer Research, and Asu Ozdaglar, deputy dean of academics for the MIT Schwarzman College of Computing and head of the Department of Electrical Engineering and Computer Science, will serve as co-faculty leads for the program.

      The new program complements a separate postdoctoral fellowship program at MIT supported by the Novo Nordisk Foundation that focuses on enabling interdisciplinary research. More

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      Four from MIT receive NIH New Innovator Awards for 2022

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      The National Institutes of Health (NIH) has awarded grants to four MIT faculty members as part of its High-Risk, High-Reward Research program.

      The program supports unconventional approaches to challenges in biomedical, behavioral, and social sciences. Each year, NIH Director’s Awards are granted to program applicants who propose high-risk, high-impact research in areas relevant to the NIH’s mission. In doing so, the NIH encourages innovative proposals that, due to their inherent risk, might struggle in the traditional peer-review process.

      This year, Lindsay Case, Siniša Hrvatin, Deblina Sarkar, and Caroline Uhler have been chosen to receive the New Innovator Award, which funds exceptionally creative research from early-career investigators. The award, which was established in 2007, supports researchers who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant.

      Lindsay Case, the Irwin and Helen Sizer Department of Biology Career Development Professor and an extramural member of the Koch Institute for Integrative Cancer Research, uses biochemistry and cell biology to study the spatial organization of signal transduction. Her work focuses on understanding how signaling molecules assemble into compartments with unique biochemical and biophysical properties to enable cells to sense and respond to information in their environment. Earlier this year, Case was one of two MIT assistant professors named as Searle Scholars.

      Siniša Hrvatin, who joined the School of Science faculty this past winter, is an assistant professor in the Department of Biology and a core member at the Whitehead Institute for Biomedical Research. He studies how animals and cells enter, regulate, and survive states of dormancy such as torpor and hibernation, aiming to harness the potential of these states therapeutically.

      Deblina Sarkar is an assistant professor and AT&T Career Development Chair Professor at the MIT Media Lab​. Her research combines the interdisciplinary fields of nanoelectronics, applied physics, and biology to invent disruptive technologies for energy-efficient nanoelectronics and merge such next-generation technologies with living matter to create a new paradigm for life-machine symbiosis. Her high-risk, high-reward proposal received the rare perfect impact score of 10, which is the highest score awarded by NIH.

      Caroline Uhler is a professor in the Department of Electrical Engineering and Computer Science and the Institute for Data, Systems, and Society. In addition, she is a core institute member at the Broad Institute of MIT and Harvard, where she co-directs the Eric and Wendy Schmidt Center. By combining machine learning, statistics, and genomics, she develops representation learning and causal inference methods to elucidate gene regulation in health and disease.

      The High-Risk, High-Reward Research program is supported by the NIH Common Fund, which oversees programs that pursue major opportunities and gaps in biomedical research that require collaboration across NIH Institutes and Centers. In addition to the New Innovator Award, the NIH also issues three other awards each year: the Pioneer Award, which supports bold and innovative research projects with unusually broad scientific impact; the Transformative Research Award, which supports risky and untested projects with transformative potential; and the Early Independence Award, which allows especially impressive junior scientists to skip the traditional postdoctoral training program to launch independent research careers.

      This year, the High-Risk, High-Reward Research program is awarding 103 awards, including eight Pioneer Awards, 72 New Innovator Awards, nine Transformative Research Awards, and 14 Early Independence Awards. These 103 awards total approximately $285 million in support from the institutes, centers, and offices across NIH over five years. “The science advanced by these researchers is poised to blaze new paths of discovery in human health,” says Lawrence A. Tabak DDS, PhD, who is performing the duties of the director of NIH. “This unique cohort of scientists will transform what is known in the biological and behavioral world. We are privileged to support this innovative science.” More

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      Differences in T cells’ functional states determine resistance to cancer therapy

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      Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in humans. Some patients with NSCLC receive a therapy called immune checkpoint blockade (ICB) that helps kill cancer cells by reinvigorating a subset of immune cells called T cells, which are “exhausted” and have stopped working. However, only about 35 percent of NSCLC patients respond to ICB therapy. Stefani Spranger’s lab at the MIT Department of Biology explores the mechanisms behind this resistance, with the goal of inspiring new therapies to better treat NSCLC patients. In a new study published on Oct. 29 in Science Immunology, a team led by Spranger lab postdoc Brendan Horton revealed what causes T cells to be non-responsive to ICB — and suggests a possible solution.

      Scientists have long thought that the conditions within a tumor were responsible for determining when T cells stop working and become exhausted after being overstimulated or working for too long to fight a tumor. That’s why physicians prescribe ICB to treat cancer — ICB can invigorate the exhausted T cells within a tumor. However, Horton’s new experiments show that some ICB-resistant T cells stop working before they even enter the tumor. These T cells are not actually exhausted, but rather they become dysfunctional due to changes in gene expression that arise early during the activation of a T cell, which occurs in lymph nodes. Once activated, T cells differentiate into certain functional states, which are distinguishable by their unique gene expression patterns.

      The notion that the dysfunctional state that leads to ICB resistance arises before T cells enter the tumor is quite novel, says Spranger, the Howard S. and Linda B. Stern Career Development Professor, a member of the Koch Institute for Integrative Cancer Research, and the study’s senior author.

      “We show that this state is actually a preset condition, and that the T cells are already non-responsive to therapy before they enter the tumor,” she says. As a result, she explains, ICB therapies that work by reinvigorating exhausted T cells within the tumor are less likely to be effective. This suggests that combining ICB with other forms of immunotherapy that target T cells differently might be a more effective approach to help the immune system combat this subset of lung cancer.

      In order to determine why some tumors are resistant to ICB, Horton and the research team studied T cells in murine models of NSCLC. The researchers sequenced messenger RNA from the responsive and non-responsive T cells in order to identify any differences between the T cells. Supported in part by the Koch Institute Frontier Research Program, they used a technique called Seq-Well, developed in the lab of fellow Koch Institute member J. Christopher Love, the Raymond A. (1921) and Helen E. St. Laurent Professor of Chemical Engineering and a co-author of the study. The technique allows for the rapid gene expression profiling of single cells, which permitted Spranger and Horton to get a very granular look at the gene expression patterns of the T cells they were studying.

      Seq-Well revealed distinct patterns of gene expression between the responsive and non-responsive T cells. These differences, which are determined when the T cells assume their specialized functional states, may be the underlying cause of ICB resistance.

      Now that Horton and his colleagues had a possible explanation for why some T cells did not respond to ICB, they decided to see if they could help the ICB-resistant T cells kill the tumor cells. When analyzing the gene expression patterns of the non-responsive T cells, the researchers had noticed that these T cells had a lower expression of receptors for certain cytokines, small proteins that control immune system activity. To counteract this, the researchers treated lung tumors in murine models with extra cytokines. As a result, the previously non-responsive T cells were then able to fight the tumors — meaning that the cytokine therapy prevented, and potentially even reversed, the dysfunctionality.

      Administering cytokine therapy to human patients is not currently safe, because cytokines can cause serious side effects as well as a reaction called a “cytokine storm,” which can produce severe fevers, inflammation, fatigue, and nausea. However, there are ongoing efforts to figure out how to safely administer cytokines to specific tumors. In the future, Spranger and Horton suspect that cytokine therapy could be used in combination with ICB.

      “This is potentially something that could be translated into a therapeutic that could increase the therapy response rate in non-small cell lung cancer,” Horton says.

      Spranger agrees that this work will help researchers develop more innovative cancer therapies, especially because researchers have historically focused on T cell exhaustion rather than the earlier role that T cell functional states might play in cancer.

      “If T cells are rendered dysfunctional early on, ICB is not going to be effective, and we need to think outside the box,” she says. “There’s more evidence, and other labs are now showing this as well, that the functional state of the T cell actually matters quite substantially in cancer therapies.” To Spranger, this means that cytokine therapy “might be a therapeutic avenue” for NSCLC patients beyond ICB.

      Jeffrey Bluestone, the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the University of California-San Francisco, who was not involved with the paper, agrees. “The study provides a potential opportunity to ‘rescue’ immunity in the NSCLC non-responder patients with appropriate combination therapies,” he says.

      This research was funded by the Pew-Stewart Scholars for Cancer Research, the Ludwig Center for Molecular Oncology, the Koch Institute Frontier Research Program through the Kathy and Curt Mable Cancer Research Fund, and the National Cancer Institute. More