Author: mantulin

New MIT initiative delves into the biology of stem cells and cancer stem cells, seeks ways to identify, purify, and propagate them.

Koch Institute

October 16, 2018

How does the body renew itself? How do cancer cells use the same or similar processes to form tumors and spread throughout the body? How might we use those processes to heal injuries or fight cancer?

A new research program at MIT is tackling fundamental biological questions about normal adult stem cells and their malignant counterparts, cancer stem cells. Launched last spring with support from Fondation MIT, the MIT Stem Cell Initiative is headed by Jacqueline Lees, the Virginia and D.K. Ludwig Professor of Cancer Research, professor of biology, and associate director of the Koch Institute for Integrative Cancer Research. Other founding members of the initiative are Robert Weinberg, a professor of biology, Whitehead Institute member, and director of the Ludwig Center at MIT; and Omer Yilmaz, an assistant professor of biology.

Rare power

Normal adult stem cells have been defined for more than a half-century. Relatively rare, they are undifferentiated cells within a tissue that divide to produce two daughter cells. One remains in the stem cell state to maintain the stem cell population, a process called self-renewal. The second daughter cell adopts a partially differentiated state, then goes on to divide and differentiate further to yield multiple cell types that form that tissue. In many fully formed adult tissues, normal stem cells divide periodically to replenish or repair the tissue. Importantly, this division is a carefully controlled process to ensure that tissues are restricted to the appropriate size and cell content.

Cancer stem cells are also of long-standing interest and share many similarities with normal adult stem cells. They perform the same division but, rather than differentiating, the additional cells produced by the second daughter cell amass to form the bulk of the tumor. Following surgery or treatment, cancer stem cells can regrow the tumor — and are frequently resistant to chemotherapy — making them especially dangerous. This unique ability of normal and cancer stem cells to both self-renew and form a tissue or tumor is referred to by researchers as “stemness,” and has important implications for biomedical applications.

Because of the key role they play in tissue maintenance and regeneration, normal stem cells hold great promise for use in repairing damaged tissues. Cancer stem cells, correspondingly, are the lifeblood of tumors. Although relatively rare within tumors, they are particularly important because they possess the ability to create tumors and are also chemotherapy-resistant. As a result, cancer stem cells are thought to be responsible for tumor recurrence after remission, and also for the formation of metastases, which account for the majority of cancer-associated deaths. Accordingly, an anti-cancer stem cell therapy that can target and kill cancer stem cells is one of the holy grails of cancer treatment — a means to suppress both tumor recurrence and metastatic disease.

Hiding in plain sight

One of the fundamental challenges to studying normal and cancer stem cells, and to ultimately harnessing that knowledge, is developing the ability to identify, purify, and propagate these cells. This has often proved tricky, as another key similarity between normal and cancer stem cells is that neither is visibly different from other cells in a tissue or tumor. Thus, a major goal in stem cell and cancer stem cell research is finding ways to distinguish these rare specimens from other cells, ideally by identifying unique surface markers that can be used to purify stem cell and cancer stem cell populations and enable their study.

The MIT Stem Cell Initiative is applying new technologies and approaches in pursuit of this goal. More specifically, the program aims to:

• identify the stem cells and cancer stem cells in various tissues and tumor types;
• determine how these cells change during aging (in the case of normal stem cells) or with disease progression (in the case of degenerative conditions and cancer); and
• determine the similarities and differences between normal and cancer stem cells, with the goal of finding vulnerabilities in cancer stem cells that can be viable and specific targets for treatment.

Ultimately, the ability to identify, purify, and establish various populations of stem cells and cancer stem cells could help researchers better understand the biology of these cells, and learn how to utilize them more effectively in regenerative medicine applications and target them in cancer.

When biology meets technology

MIT Stem Cell Initiative studies focus on normal and cancer stem cells of epithelial tissues. Epithelia are one of four general tissue types in the body; they line most organs and are where the vast majority of cancers arise. Epithelial cells from different organs share some biological properties, but also have distinct differences reflecting the organ’s specific role and/or environment. In particular, the MIT Stem Cell Initiative has focused on the breast and colon, as these tissues are quite different from each other, yet each constitutes a major portion of cancer incidence.

New technologies are enabling the researchers to make significant headway in these investigations, progress that was not feasible just a few years ago. Specifically, they are using a combination of specially cultured cells, sophisticated and highly controllable mouse models of cancer, and single-cell RNA sequencing and computational analysis techniques that are uniquely suited to extracting a great deal of information from the relatively small number of stem cells.

While breast and colon work is ongoing, MIT Stem Cell Initiative members are planning studies of additional tissues and recruiting collaborators for pilot projects. The results of the researchers’ studies will advance understandings of stem cell regulation and may ultimately lead to advances in tissue regeneration and/or cancer analysis and treatment.

Lustgarten Foundation names MIT laboratory to improve understanding and treatment of a deadly disease

Erika Reinfeld | Koch Institute

October 12, 2018

Genetically complex and hard to detect in its early stages, pancreatic cancer is the fourth leading cause of cancer mortality in the U.S. It is also a long-standing staple of the MIT cancer research portfolio, with multiple active projects at the Koch Institute and beyond seeking to transform the way the disease is studied and treated.

On Sept. 21, the Lustgarten Foundation, the nation’s largest private funder of pancreatic cancer research, honored MIT’s commitment to pancreatic cancer research with the naming of the Lustgarten Laboratory for Pancreatic Cancer Research at MIT. The Lustgarten Laboratory is headed by Tyler Jacks, director of the Koch Institute and the David H. Koch Professor of Biology.

The Lustgarten Foundation’s investment will support postdocs, graduate students, technicians and a senior scientist for its duration. The Lustgarten Lab’s goals are to better understand the immunological conditions and genetic events that contribute to the development of pancreatic cancer, to study the disease on a single-cell level in both humans and mouse models, and to develop novel high throughput tools for culture and drug testing using mini-organs known as organoids.

The Jacks lab is ideally suited for this massive undertaking, thanks to its solid portfolio of pancreatic cancer research, developed with the support of the Lustgarten Foundation and others, and its deep connections with both biology and engineering laboratories at the Koch Institute and across the MIT campus.

At the dedication ceremony, David Tuveson, the chief scientist of the Lustgarten Foundation, praised the Jacks lab’s “collective skills and talents” and its “highly collaborative approach” as the driving force behind many advances in pancreatic cancer research over the last two decades, a legacy of which Tuveson is part.

Of mice and mentorship

Jacks is widely considered a pioneer in the development of engineered mouse models of human cancers. It was in his laboratory, then a part of MIT’s Center for Cancer Research, the predecessor to the Koch Institute, that Tuveson began work on what would become the KPC mouse model of pancreatic ductal adenocarcinoma (PDAC). The model, which centers around the exploitation of commonly mutated genes Kras (a cancer driver) and p53 (a tumor suppressor) is now the gold standard for pre-clinical studies of the disease. With it, scientists can trace the development of tumors inside a living pancreas from a single mutated cell to metastatic invasion of distant organs.

In a way, the model presents a microcosm of the robust training environment within the Jacks Lab. Current postdoctoral researcher and designated Lustgarten Lab lead scientist Will Freed-Pastor praises his mentor’s willingness to step back and give his mentees space to make their own marks on the world. “Training future leaders,” he says, “is one of Tyler’s most valuable contributions to the field.”

With the new resources from Lustgarten, Jacks looks forward to bringing even more researchers into field and applying knowledge gained from his lab’s work in lung cancer, immunology, and gene editing to the unique challenges of pancreatic tumors.

“We have a formidable team and it is only going to get stronger,” Jacks says. “We are grateful for the Lustgarten Foundation’s investment in our work as it allows us to recruit new investigators from across MIT who have never worked in pancreatic cancer before but whose tools and approaches will help us develop new treatment paradigms for early diagnosis and intervention.”

A signature investment

The naming of the Lustgarten Laboratory for Pancreatic Cancer Research at MIT is happening side-by-side with that of Brian Wolpin’s lab across the river at Dana-Farber Cancer Institute. In addition to serving as the Jacks lab’s clinical liaison, Wolpin has collaborated on pancreatic cancer research with Matthew Vander Heiden, professor of biology and associate director of the Koch Institute.

The dual investment represents a milestone for the Lustgarten Foundation — the second and third lab spaces dedicated to pancreatic cancer research — in its 20th anniversary year. Tuveson heads the first, Cold Spring Harbor Laboratory, where he is now a professor and the director of the Cancer Center.

“We are so excited to usher in a new era of pancreatic cancer research,” says Kerri Kaplan, president and chief executive officer of the Lustgarten Foundation. “Twenty years ago, this was truly an ‘orphan’ disease, but thanks to the commitment and innovative approaches of these researchers at MIT and beyond, we are rapidly expanding our knowledge and ability to improve patient outcomes.”

As a researcher himself and the shepherd of MIT’s transition from the Center for Cancer Research to the Koch Institute, Jacks has long sought to balance basic science research with clinical applications. Pancreatic cancer was among the first disease areas identified as a priority for the Bridge Project, the Koch Institute’s signature collaboration between MIT and Dana-Farber/Harvard Cancer Center. The Lustgarten Foundation was among the primary supporters of the Bridge Project in its inaugural year. Even with these resources, however, pancreatic cancer continues to be a difficult disease to approach.

Jacks and his colleagues describe the Lustgarten investment as high-risk, high-reward — an innovation fund to move beyond incremental improvements at both the bench and the bedside.

“This gives us the freedom to ask very challenging questions about cancer cells themselves and the immune system,” Freed-Pastor says.

Jacks agrees. “This is exactly the right time for this work,” he says. “We understand so much more about this disease than we did two decades ago, and we now have the teams and technologies to transform that knowledge into actionable solutions for patients. We are honored by the Lustgarten Foundation’s trust in that endeavor.”

MacArthur “geniuses” in machine learning and synthetic biology to serve as faculty co-leads; Nobel laureate to chair advisory board of new research center.

School of Engineering

October 3, 2018

Regina Barzilay and James Collins have been named the faculty co-leads of the Abdul Latif Jameel Clinic for Machine Learning in Health, or J-Clinic, effective immediately, announced Anantha Chandrakasan, dean of the School of Engineering and chair of J-Clinic. Institute Professor Philip Sharp will also serve as the chair of J-Clinic’s advisory board.

Launched on Sept. 17, J-Clinic is the fourth major collaborative effort between MIT and Community Jameel, the social enterprise organization founded and chaired by Mohammed Abdul Latif Jameel ’78. A key part of the MIT Quest for Intelligence, J-Clinic will focus on developing machine learning technologies to revolutionize the prevention, detection, and treatment of disease. It will concentrate on creating and commercializing high-precision, affordable, and scalable machine learning technologies in areas of health care ranging from diagnostics to pharmaceuticals.

“J-Clinic will make a difference in patients’ lives everywhere from major hospitals to villages in the developing world. It will draw on MIT’s longstanding strengths in biomedical fields, on our decades of collaboration with the concentration of world-class teaching hospitals in Boston, and on our proximity to the world’s major biotech companies in Kendall Square,” says Chandrakasan.

Barzilay is the Delta Electronics Professor of Electrical Engineering and Computer Science at MIT and an investigator at the Computer Science and Artificial Intelligence Laboratory (CSAIL). She also co-directs a Machine Learning for Pharmaceutical Discovery and Synthesis Consortium that aims to develop AI algorithms for automation of drug design. Barzilay is a recipient of a MacArthur Fellowship, the National Science Foundation CAREER award, the MIT Technology Review TR35 Award, and a Microsoft Faculty Fellowship. She was also elected an Association of Computational Linguistics Fellow and an Association for the Advancement of Artificial Intelligence Fellow. Barzilay received her BS and MS from Ben-Gurion University of the Negev, Israel. She earned a PhD in computer science from Columbia University and did her postdoctoral work at Cornell University.

“Today almost every aspect of our life is driven by machine learning predictions — be it travel, banking or entertainment. The only area where we do not benefit from this powerful technology is the one which impacts us the most, our health care,” says Barzilay. “The goal of the center is to change it. We aim to bring the best of AI technology we develop in our labs at MIT to hospitals and clinics in the U.S. and around the world.”

Collins is the Termeer Professor of Medical Engineering and Science, a professor of biological engineering at MIT, and a member of the Harvard-MIT Health Sciences and Technology faculty. He is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University and an Institute Member of the Broad Institute of MIT and Harvard. Collins’s numerous honors include a Rhodes Scholarship, a MacArthur Fellowship, and an NIH Director’s Pioneer Award. He is an elected member of all three national academies: the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine. He is also a member of the American Academy of Arts and Sciences, the National Academy of Inventors, and the World Academy of Sciences. Collins earned an BA in physics from the College of the Holy Cross and a PhD in medical engineering from the University of Oxford.

“Machine learning is the defining technology of this decade, though its impact on health care thus far has been meager. Through J-Clinic, we plan to train the next generation of scientists and engineers at the interface of machine learning and biomedicine, so as to enable the development of innovative AI-based technologies that can be used to improve lives of patients around the world,” says Collins. “I am honored to have the opportunity to work with Regina, Phil, and Anantha on this exciting new venture.”

Sharp is an Institute Professor at MIT in the Koch Institute for Integrative Cancer Research. In 1993 he shared the Nobel Prize in physiology or medicine for the discovery of split genes and in 2004 was awarded the National Medal of Science. He co-founded Biogen and served on its board for 29 years. In 2002, he co-founded Alnylam Pharmaceuticals and continues to serve on its board. He is chair of the scientific advisory committee of Stand Up to Cancer and a proponent of Convergence, the engagement of engineering, computational and physical sciences in biomedical science.

“The J-Clinic is an exciting opportunity for MIT scientists to bring machine learning to health care. I look forward to chairing its advisory group to accelerate its growth and impact,” says Sharp.

J-Clinic’s efforts will be global and multifaceted, says Chandrakasan. “J-Clinic’s remarkable leadership team will bring the world many exciting new healthcare solutions,” he says.

MIT.nano building, the largest of its kind, will usher in a new age of nanoscale advancements.

David L. Chandler | MIT News Office

September 24, 2018

Nanotechnology, the cutting-edge research field that explores ultrasmall materials, organisms, and devices, has now been graced with the largest, most sophisticated, and most accessible university research facility of its kind in the U.S.: It is the new $400 million MIT.nano building, which will have its official opening ceremonies next week.

The state-of-the-art facility includes two large floors of connected clean-room spaces that are open to view from the outside and available for use by an extraordinary number and variety of researchers across the Institute. It also features a whole floor of undergraduate chemistry teaching labs, and an ultrastable basement level dedicated to electron microscopes and other exquisitely sensitive imaging and measurement tools.

“In recent decades, we have gained the ability to see into the nanoscale with breathtaking precision. This insight has led to the development of tools and instruments that allow us to design and manipulate matter like nature does, atom by atom and molecule by molecule,” says Vladimir Bulović, the Fariborz Maseeh Professor in Emerging Technology and founding director of MIT.nano. “MIT.nano has arrived on campus at the dawn of the Nano Age. In the decades ahead, its open-access facilities for nanoscience and nanoengineering will equip our community with instruments and processes that can further harness the power of nanotechnology in service to humanity’s greatest challenges.”

“In terms of vibrations and electromagnetic noise, MIT.nano may be the quietest space on campus. But in a community where more than half of recently tenured faculty do work at the nanoscale, MIT.nano’s superb shared facilities guarantee that it will become a lively center of community and collaboration, says MIT President L. Rafael Reif. “I am grateful to the exceptional team — including Provost Martin Schmidt, Founding Director Vladimir Bulovic, and many others — that delivered this extraordinarily sophisticated building on an extraordinarily inaccessible construction site, making a better MIT so we can help to make a better world.”

Accessible and flexible

The 214,000-square-foot building, with its soaring glass facades, sophisticated design and instrumentation, and powerful air-exchange systems, lies at the heart of campus and just off the Infinite Corridor. It took shape during six years of design and construction, and was delivered exactly on schedule and on budget, a rare achievement for such a massive and technologically complex construction project.

“MIT.nano is a game-changer for the MIT research enterprise,” says Vice President for Research Maria Zuber. “It will provide measurement and imaging capabilities that will dramatically advance science and technology in disciplines across the Institute.”

At the heart of the building are two levels of clean rooms — research environments in which the air is continuously scrubbed and replaced to maintain a standard that allows no more than 100 particles of  0.5 microns or larger within a cubic foot of air. To achieve such cleanliness, work on the building has included strict filtration measures and access restrictions for more than a year, and at the moment, with the spaces not yet in full use, they far exceed that standard.

All of the lab and instrumentation spaces in the building will be used as shared facilities, accessible to any MIT researcher who needs the specialized tools that will be installed there over the coming months and years. The tools will be continually upgraded, as the building is designed to be flexible and ready for the latest advances in equipment for making, studying, measuring, and manipulating nanoscale objects — things measured in billionths of a meter, whether they be technological, biological, or chemical.

Many of the tools and instruments to be installed in MIT.nano are so costly and require so much support in services and operations that they would likely be out of reach for a single researcher or team. One of the instruments now installed and being calibrated in the basement imaging and metrology suites — sitting atop a 5-million-pound slab of concrete to provide the steadiest base possible — is a cryogenic transmission electron microscope. This multimillion dollar instrument is hosted in an equally costly room with fine-tuned control of temperature and humidity, specialized features to minimize the mechanical and electromagnetic interference, and a technical support team. The device, one of two currently being installed in MIT.nano, will enable detailed 3-D observations of cells or materials held at very low liquid-nitrogen temperatures, giving a glimpse into the exquisite nanoscale features of the soft-matter world.

Almost half of the MIT.nano’s footage is devoted to lab space — 100,000 square feet of it — which is about 100 times larger in size than the typical private lab space of a young experimental research group at MIT, Bulović says. Private labs typically take a few years to build out, and once in place often house valuable equipment that is idle for at least part of the time. It will similarly take a few years to fully build out MIT.nano’s shared labs, but Bulović expects that the growing collection of advanced instruments will rarely be idle. The instrument sets will be selected and designed to drastically improve a researcher’s ability to hit the ground running with access to the best tools from the start, he says.

Principal investigators often “find there’s a benefit to contributing tools to the community so they can be shared and perfected through their use,” Bulović says. “They recognize that as these tools are not needed for their own work 24/7, attracting additional instrument users can generate a revenue stream for the tool, which supports maintenance and future upgrades while also enhancing the research output of labs that would not have access to those tools otherwise.”

A facility sized to meet demand

Once MIT.nano is fully outfitted, over 2,000 MIT faculty and researchers are expected to use the new facilities every year, according to Bulović. Besides its clean-room floors, instrumentation floor, chemistry labs, and the top-floor prototyping labs, the new building also houses a unique facility at MIT: a two-story virtual-reality and visualization space called the Immersion Lab. It could be used by researchers studying subcellular-resolution images of biological tissues or complex computer simulations, or planetary scientists walking through a reproduced Martian surface looking for geologically interesting sites; it may even lend itself to artistic creations or performances, he says. “It’s a unique space. The beauty of it is it will connect to the huge datasets” coming from instruments such as the cryoelectron microscopes, or from simulations generated by artificial intelligence labs, or from other external datasets.

The chemistry labs on the building’s fifth floor, which can accommodate a dozen classes of a dozen students each, are already fully outfitted and in full use for this fall. The labs allow undergraduate chemistry students an exceptionally full and up-to-date experience of lab processes and tools.

“The Department of Chemistry is delighted to move into our new state-of-the-art Undergraduate Teaching Laboratories (UGTL) in MIT.nano,” says department head Timothy Jamison. “The synergy between our URIECA curriculum and this new space enables us to provide an even stronger educational foundation in experimental chemistry to our students. Vladimir Bulović and the MIT.nano team have been wonderful partners at all stages — throughout the design, construction, and move — and we look forward to other opportunities resulting from this collaboration and the presence of our UGTL in MIT.nano.”

The building itself was designed to be far more open and accessible than any comparable clean-room facility in the world. Those outside the labs can watch through MIT.nano’s many windows and see the use of these specialized devices and how such labs work. Meanwhile, researchers themselves can more easily interact with each other and see the sunshine and the gently waving bamboo plants outdoors as a reminder of the outside world that they are working to benefit.

A courtyard path on the south side of the building is named the Improbability Walk, in honor of the late MIT Institute Professor Emerita Mildred “Millie” Dresselhaus. The name is a nod to a statement by the beloved mentor, collaborator, teacher, and world-renowned pioneer in solid-state physics and nanoscale engineering, who once said, “My background is so improbable — that I’d be here from where I started.”

Those who walk through the building’s sunlight-soaked corridors and galleries will notice walls surfaced with panels of limestone from the Yangtze Platform of southwestern China. The limestone’s delicate patterns of fine horizontal lines are made up of tiny microparticles, such as bits of ancient microorganisms, laid down at the bottom of primeval waters before dinosaurs roamed the Earth. The very newest marvels to emerge in nanotechnology will thus be coming into existence right within view of some of their most ancient minuscule precursors.

New faculty join the departments of Biology, Brain and Cognitive Sciences, Chemistry, Physics, Mathematics, and Earth, Atmospheric and Planetary Sciences.

School of Science

September 21, 2018

The MIT School of Science recently welcomed 10 new professors in the departments of Biology Brain and Cognitive Sciences, Chemistry, Physics, Mathematics, and Earth, Atmospheric and Planetary Sciences.

Tristan Collins conducts research at the intersection of geometric analysis, partial differential equations, and algebraic geometry. In joint work with Valentino Tosatti, Collins described the singularity formation of the Ricci flow on Kahler manifolds in terms of algebraic data. In recent work with Gabor Szekelyhidi, he gave a necessary and sufficient algebraic condition for existence of Ricci-flat metrics, which play an important role in string theory and mathematical physics. This result lead to the discovery of infinitely many new Einstein metrics on the 5-dimensional sphere. With Shing-Tung Yau and Adam Jacob, Collins is currently studying the relationship between categorical stability conditions and existence of solutions to differential equations arising from mirror symmetry.

Collins earned his BS in mathematics at the University of British Columbia in 2009, after which he completed his PhD in mathematics at Columbia University in 2014 under the direction of Duong H. Phong. Following a four-year appointment as a Benjamin Peirce Assistant Professor at Harvard University, Collins joins MIT as an assistant professor in the Department of Mathematics.

Julien de Wit develops and applies new techniques to study exoplanets, their atmospheres, and their interactions with their stars. While a graduate student in the Sara Seager group at MIT, he developed innovative analysis techniques to map exoplanet atmospheres, studied the radiative and tidal planet-star interactions in eccentric planetary systems, and constrained the atmospheric properties and mass of exoplanets solely from transmission spectroscopy. He plays a critical role in the TRAPPIST/SPECULOOS project, headed by Université of Liège, leading the atmospheric characterization of the newly discovered TRAPPIST-1 planets, for which he has already obtained significant results with the Hubble Space Telescope. De Wit’s efforts are now also focused on expanding the SPECULOOS network of telescopes in the northern hemisphere to continue the search for new potentially habitable TRAPPIST-1-like systems.

De Wit earned a BEng in physics and mechanics from the Université de Liège in Belgium in 2008, an MS in aeronautic engineering and an MRes in astrophysics, planetology, and space sciences from the Institut Supérieur de l’Aéronautique et de l’Espace at the Université de Toulouse, France in 2010; he returned to the Université de Liège for an MS in aerospace engineering, completed in 2011. After finishing his PhD in planetary sciences in 2014 and a postdoc at MIT, both under the direction of Sara Seager, he joins the MIT faculty in the Department of Earth, Atmospheric and Planetary Sciences as an assistant professor.

Ila Fiete uses computational and theoretical tools to better understand the dynamical mechanisms and coding strategies that underlie computation in the brain, with a focus on elucidating how plasticity and development shape networks to perform computation and why information is encoded the way that it is. Her recent focus is on error control in neural codes, rules for synaptic plasticity that enable neural circuit organization, and questions at the nexus of information and dynamics in neural systems, such as understand how coding and statistics fundamentally constrain dynamics and vice-versa.

After earning a BS in mathematics and physics at the University of Michigan, Fiete obtained her PhD in 2004 at Harvard University in the Department of Physics. While holding an appointment at the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara from 2004 to 2006, she was also a visiting member of the Center for Theoretical Biophysics at the University of California at San Diego. Fiete subsequently spent two years at Caltech as a Broad Fellow in brain circuitry, and in 2008 joined the faculty of the University of Texas at Austin. She joins the MIT faculty in the Department of Brain and Cognitive Sciences as an associate professor with tenure.

Ankur Jain explores the biology of RNA aggregation. Several genetic neuromuscular disorders, such as myotonic dystrophy and amyotrophic lateral sclerosis, are caused by expansions of nucleotide repeats in their cognate disease genes. Such repeats cause the transcribed RNA to form pathogenic clumps or aggregates. Jain uses a variety of biophysical approaches to understand how the RNA aggregates form, and how they can be disrupted to restore normal cell function. Jain will also study the role of RNA-DNA interactions in chromatin organization, investigating whether the RNA transcribed from telomeres (the protective repetitive sequences that cap the ends of chromosomes) undergoes the phase separation that characterizes repeat expansion diseases.

Jain completed a bachelor’s of technology degree in biotechnology and biochemical engineering at the Indian Institute of Technology Kharagpur, India in 2007, followed by a PhD in biophysics and computational biology at the University of Illinois at Urbana-Champaign under the direction of Taekjip Ha in 2013. After a postdoc at the University of California at San Francisco, he joins the MIT faculty in the Department of Biology as an assistant professor with an appointment as a member of the Whitehead Institute for Biomedical Research.

Kiyoshi Masui works to understand fundamental physics and the evolution of the universe through observations of the large-scale structure — the distribution of matter on scales much larger than galaxies. He works principally with radio-wavelength surveys to develop new observational methods such as hydrogen intensity mapping and fast radio bursts. Masui has shown that such observations will ultimately permit precise measurements of properties of the early and late universe and enable sensitive searches for primordial gravitational waves. To this end, he is working with a new generation of rapid-survey digital radio telescopes that have no moving parts and rely on signal processing software running on large computer clusters to focus and steer, including work on the Canadian Hydrogen Intensity Mapping Experiment (CHIME).

Masui obtained a BSCE in engineering physics at Queen’s University, Canada in 2008 and a PhD in physics at the University of Toronto in 2013 under the direction of Ue-Li Pen. After postdoctoral appointments at the University of British Columbia as the Canadian Institute for Advanced Research Global Scholar and the Canadian Institute for Theoretical Astrophysics National Fellow, Masui joins the MIT faculty in the Department of Physics as an assistant professor.

Phiala Shanahan studies theoretical nuclear and particle physics, in particular the structure and interactions of hadrons and nuclei from the fundamental (quark and gluon) degrees of freedom encoded in the Standard Model of particle physics. Shanahan’s recent work has focused on the role of gluons, the force carriers of the strong interactions described by quantum chromodynamics (QCD), in hadron and nuclear structure by using analytic tools and high-performance supercomputing. She recently achieved the first calculation of the gluon structure of light nuclei, making predictions that will be testable in new experiments proposed at Jefferson National Accelerator Facility and at the planned Electron-Ion Collider. She has also undertaken extensive studies of the role of strange quarks in the proton and light nuclei that sharpen theory predictions for dark matter cross-sections in direct detection experiments. To overcome computational limitations in QCD calculations for hadrons and in particular for nuclei, Shanahan is pursuing a program to integrate modern machine learning techniques in computational nuclear physics studies.

Shanahan obtained her BS in 2012 and her PhD in 2015, both in physics, from the University of Adelaide. She completed postdoctoral work at MIT in 2017, then held a joint position as an assistant professor at the College of William and Mary and senior staff scientist at the Thomas Jefferson National Accelerator Facility until 2018. She returns to MIT in the Department of Physics as an assistant professor.

Nike Sun works in probability theory at the interface of statistical physics and computation. Her research focuses in particular on phase transitions in average-case (randomized) formulations of classical computational problems. Her joint work with Jian Ding and Allan Sly establishes the satisfiability threshold of random k-SAT for large k, and relatedly the independence ratio of random regular graphs of large degree. Both are long-standing open problems where heuristic methods of statistical physics yield detailed conjectures, but few rigorous techniques exist. More recently she has been investigating phase transitions of dense graph models.

Sun completed BA mathematics and MA statistics degrees at Harvard in 2009, and an MASt in mathematics at Cambridge in 2010. She received her PhD in statistics from Stanford University in 2014 under the supervision of Amir Dembo. She held a Schramm fellowship at Microsoft New England and MIT Mathematics in 2014-2015 and a Simons postdoctoral fellowship at the University of California at Berkeley in 2016, and joined the Berkeley Department of Statistics as an assistant professor in 2016. She returns to the MIT Department of Mathematics as an associate professor with tenure.

Alison Wendlandt focuses on the development of selective, catalytic reactions using the tools of organic and organometallic synthesis and physical organic chemistry. Mechanistic study plays a central role in the development of these new transformations. Her projects involve the design of new catalysts and catalytic transformations, identification of important applications for selective catalytic processes, and elucidation of new mechanistic principles to expand powerful existing catalytic reaction manifolds.

Wendlandt received a BS in chemistry and biological chemistry from the University of Chicago in 2007, an MS in chemistry from Yale University in 2009, and a PhD in chemistry from the University of Wisconsin at Madison in 2015 under the direction of Shannon S. Stahl. Following an NIH Ruth L. Krichstein Postdoctoral Fellowship at Harvard University, Wendlandt joins the MIT faculty in the Department of Chemistry as an assistant professor.

Chengyang Xu specializes in higher-dimensional algebraic geometry, an area that involves classifying algebraic varieties, primarily through the minimal model program (MMP). MMP was introduced by Fields Medalist S. Mori in the early 1980s to make advances in higher dimensional birational geometry. The MMP was further developed by Hacon and McKernan in the mid-2000s, so that the MMP could be applied to other questions. Collaborating with Hacon, Xu expanded the MMP to varieties of certain conditions, such as those of characteristic p, and, with Hacon and McKernan, proved a fundamental conjecture on the MMP, generating a great deal of follow-up activity. In collaboration with Chi Li, Xu proved a conjecture of Gang Tian concerning higher-dimensional Fano varieties, a significant achievement. In a series of papers with different collaborators, he successfully applied MMP to singularities.

Xu received his BS in 2002 and MS in 2004 in mathematics from Peking University, and completed his PhD at Princeton University under János Kollár in 2008. He came to MIT as a CLE Moore Instructor in 2008-2011, and was subsequently appointed assistant professor at the University of Utah. He returned to Peking University as a research fellow at the Beijing International Center of Mathematical Research in 2012, and was promoted to professor in 2013. Xu joins the MIT faculty as a full professor in the Department of Mathematics.

Zhiwei Yun’s research is at the crossroads between algebraic geometry, number theory, and representation theory. He studies geometric structures aiming at solving problems in representation theory and number theory, especially those in the Langlands program. While he was a CLE Moore Instructor at MIT, he started to develop the theory of rigid automorphic forms, and used it to answer an open question of J-P Serre on motives, which also led to a major result on the inverse Galois problem in number theory. More recently, in his joint work with Wei Zhang, they give geometric interpretation of higher derivatives of automorphic L- functions in terms of intersection numbers, which sheds new light on the geometric analogue of the Birch and Swinnerton-Dyer conjecture.

Yun earned his BS at Peking University in 2004, after which he completed his PhD at Princeton University in 2009 under the direction of Robert MacPherson. After appointments at the Institute for Advanced Study and as a CLE Moore Instructor at MIT, he held faculty appointments at Stanford and Yale. He returned to the MIT Department of Mathematics as a full professor in the spring of 2018.

Three MIT postdocs earn competitive Howard Hughes Medical Institute fellowships that support diversity in the sciences.

David Orenstein | Erika Reinfeld | Lisa Girard | Picower Institute for Learning and Memory

September 12, 2018

In recognition of their exceptional potential to be leaders in the life sciences, three MIT postdocs at the Koch, Picower, and Whitehead institutes at MIT are among 15 young researchers to earn Hanna Gray Fellowships from the Howard Hughes Medical Institute (HHMI), the Chevy Chase, Maryland-based organization has announced.

The early-career awards are given to individuals around the U.S. who are from racial, gender, ethnic, and other groups underrepresented in the life sciences. The fellowships will support their work with up to $1.4 million in funding over eight years, enough to last well into a tenure track position after they complete their postdoctoral studies.

“This program will help us retain the most diverse talent in science,” HHMI President Erin O’Shea said in the announcement. “We feel it’s critically important in academia to have exceptional people from all walks of life, all cultures, and all backgrounds — people who can inspire the next generation of scientists.”

MIT’s three Hanna Gray Fellows are Matheus Victor, who works in the lab of Li-Huei Tsai in the Picower Institute for Learning and Memory; Quinton Smith, who works in Sangeeta Bhatia’s lab at the Koch Institute for Integrative Cancer Research; and Jarrett Smith, who works in the David Bartel Lab at the Whitehead Institute for Biomedical Research.

Jarrett Smith

Jarrett Smith was always interested in science, but no one in his family had ever received a PhD, making biology research feel like an unlikely career path for him. Nevertheless, he followed his passion, which led him to his PhD program at the Johns Hopkins University School of Medicine. Despite his strong academic performance, Smith began graduate school with doubts about his ability to become a scientist. His mentors were incredible teachers, he says, but their self-assuredness could be intimidating.

“They were absolutely my role models, but I didn’t think of them as having gone through what I was going through. In the first few years, I felt like I had a lot of catching up to do,” Smith says.

Now, as a postdoc in David Bartel’s lab at the Whitehead Institute, he studies how cells respond to stress. When a cell is exposed to environmental stressors such as heat, UV radiation, or viral infection, proteins and RNAs in the cell may clump together into dense aggregates called stress granules. The exact function of stress granules and their potential role in disease are unknown, so Smith is investigating changes in the cell linked to their formation. His findings could shed light on a potential role for stress granules in cancer, infection, and neurodegenerative disease.

“I’m grateful for the support that the fellowship will provide during the formative years of my career,” Smith says. “This kind of opportunity gives you the confidence to set ambitious research goals and find out what you can accomplish.”

Quinton Smith

Quinton Smith fell in love with regenerative medicine the summer after his sophomore year of college. Working on an epidemiological study at the University of New Mexico Cancer Research Facility in his hometown of Albuquerque, Smith found himself extracting DNA from hundreds of mouthwash samples in order to answer overarching questions about the biological and behavioral factors that contribute to cancer.

The experience left him with a strong appreciation for the complexities of human disease, and an even stronger desire to translate his knowledge into better interventions for patients. To this end, he completed his PhD at Johns Hopkins University, exploring a variety of engineering techniques to control and probe the differentiation of pluripotent stem cells. In 2017 he joined the laboratory of Sangeeta Bhatia, the John J. and Dorothy Wilson Professor at MIT’s Institute for Medical Engineering and Science and Electrical Engineering and Computer Science and director of the Marble Center for Cancer Nanomedicine.

By then, the lab had already demonstrated success developing implantable “mini-livers” able to engraft and respond to regenerative stimuli in mice with damaged livers. However, the design is incomplete and Smith wants to incorporate a biliary tree to guide hepato-secreted bile acids that aid in the breakdown of fats but pose as a potential toxin to these therapeutic grafts. He is working to build such a tree with an unexpected tool — microfluidic vessels, forged by biomaterial-encapsulated acupuncture needles that, once removed, can be used to create a network of biliary-lined tunnels through which bile can flow.

The ability to bolster cutting-edge research is but one benefit of Smith’s HHMI award. He and Bhatia praise the seeds the program plants within the academic environment, providing much-needed visibility that achievements in STEM are, and will continue to be, driven by scientists from all walks of life.

“I think this program is directing a shift in what a researcher looks like, offering a motivating exposure to the next generation of students who have the potential to impact science regardless of their background,” Smith says. “This is an incredible and humbling opportunity to explore my passion for the promise of regenerative medicine, and to have the resources to tinker and extend my creativity around translational research.”

Matheus Victor

As a graduate student at Washington University in St. Louis, Matheus Victor, a native of Recife, Brazil, who came to Florida at the age of 15, learned that in the U.S., Latino immigrants are rare among scientific researchers. But there he was, pursuing his dreams to become a neuroscientist. The realization inspired him to lead a Latin American student group at WashU and to conduct outreach activities including creating bilingual curricula for local students.

“I was so privileged to be in a top tier graduate program pursuing my interest,” he said. “How many people get to pursue an interest? We live in a world where you have to earn money and you have to feed your family.”

Now he’s a new postdoc at MIT’s Picower Institute for Learning and Memory in the lab of Institute director and Picower Professor Li-Huei Tsai, with a prestigious fellowship that will support him as he embarks on two investigations of the role of specific cell types in brain aging and cognitive decline.

In one, he plans to turn human induced pluripotent stem cells into microglia, an immune cell of the nervous system increasingly implicated in Alzheimer’s disease, and implant them in the brains of mice where the original microglia have been removed. With this chimera model Victor can test how microglia with different genetic variations act in a mammalian brain to see how those variations might contribute to disease pathology.

In the other, he is interested in studying how inhibitory interneurons change in the aging brain. The neurons are of particular interest because they are the source of a crucial brain rhythm that is notably reduced in Alzheimer’s disease. Understanding more about how they function and falter could help explain that important change.