Angelika Amon and Dina Katabi named Carnegie Corporation “Great Immigrants”

MIT biologist and electrical engineer are two of 38 naturalized U.S. citizens honored for contributions to American society.

MIT News Office
July 2, 2019

MIT professors Angelika Amon and Dina Katabi have been named to the Carnegie Corporation of New York’s 2019 list of Great Immigrants, Great Americans. These 38 naturalized U.S. citizens are noted as individuals who “strengthen America’s economy, enrich our culture and communities, and invigorate our democracy through their lives, their work, and their examples.”

Angelika Amon, who hails from Austria, is a molecular and cell biologist who studies cell growth and division and how errors in this process — specifically abnormal numbers of chromosomes — contribute to cancer, aging, and birth defects.

Amon arrived in Cambridge, Massachusetts, from Vienna in 1994 to complete a two-year postdoctoral fellowship at the Whitehead Institute for Biomedical Research; she was subsequently named a Whitehead Fellow for three years. Amon then joined the MIT Center for Cancer Research, now the Koch Institute for Integrative Cancer Research at MIT, and MIT’s Department of Biology in 1999. She became a full professor in 2007 and is currently the Kathleen and Curtis Marble Professor in Cancer Research, a Howard Hughes Medical Institute investigator, the co-associate director of the Glenn Center for Science of Aging Research at MIT, and the inaugural director of the Alana Down Syndrome Center at MIT. Her most recent awards include the 2019 Vilcek Prize in Biomedical Science and the 2019 Breakthrough Prize in Life Sciences.

Dina Katabi, who was born in Syria, is an engineer who works to improve the speed, reliability, and security of wireless networks. She is especially known for her work on a wireless system that can track human movement even through walls — a technology that has great potential for medical use.

Katabi joined the Department of Electrical Engineering and Computer Science faculty in 2003. She is a principal investigator in the Computer Science and Artificial Intelligence Laboratory (CSAIL), as well as director of the Networks at MIT research group and co-director of the MIT Center for Wireless Networks and Mobile Computing, both in CSAIL. Among other honors, Katabi has received a MacArthur Fellowship (sometimes called a “genius grant”), the Association for Computing Machinery (ACM) Prize in Computing, the ACM Grace Murray Hopper Award, a Test of Time Award from the ACM’s Special Interest Group on Data Communications, a National Science Foundation CAREER Award, and a Sloan Research Fellowship. She is an ACM Fellow and was elected to the National Academy of Engineering. She earned a bachelor’s degree from Damascus University and master’s and PhD degrees from MIT.

The Carnegie Corporation celebrates its Great Immigrants every Fourth of July as a way to honor exemplary naturalized U.S. citizens. The organization has named nearly 600 individuals to its list since 2006. Past MIT honorees include Professor Daron Acemoglu (Turkey), Professor Nergis Mavalvala (Pakistan), President L. Rafael Reif (Venezuela), Professor Emeritus Rainer Weiss (Germany), and Professor Feng Zhang (China).

MIT Energy Initiative awards seven Seed Fund grants for early-stage energy research

Annual MITEI awards support research on methane conversion, efficient energy provision, plastics recycling, and more.

MIT Energy Initiative
July 2, 2019

The MIT Energy Initiative (MITEI) recently awarded seven grants totaling approximately $1 million through its Seed Fund Program, which supports early-stage innovative energy research at MIT through an annual competitive process.

“Supporting basic research has always been a core component of MITEI’s mission to transform and decarbonize global energy systems,” says MITEI Director Robert C. Armstrong, the Chevron Professor of Chemical Engineering. “This year’s funded projects highlight just a few examples of the many ways that people working across the energy field are researching vital topics to create a better world.”

The newly awarded projects will address topics such as developing efficient strategies for recycling plastics, improving the stability of high-energy metal-halogen flow batteries, and increasing the potential efficiency of silicon solar cells to accelerate the adoption of photovoltaics. Awardees include established energy faculty members and others who are new to the energy field, from disciplines including applied economics, chemical engineering, biology, and other areas.

Demand-response policies and incentives for energy efficiency adoption

Most of today’s energy growth is occurring in developing countries. Assistant Professor Namrata Kala and Professor Christopher Knittel, both of whom focus on applied economics at the MIT Sloan School of Management, will use their grant to examine key policy levers for meeting electricity demand and renewable energy growth without jeopardizing system reliability in the developing world.

Kala and Knittel plan to design and run a randomized control trial in New Delhi, India, in collaboration with a large Indian power company. “We will estimate the willingness of firms to enroll in services that reduce peak consumption, and also promote energy efficiency,” says Kala, the W. Maurice Young (1961) Career Development Professor of Management. “Estimating the costs and benefits of such services, and their allocation across customers and electricity providers, can inform policies that promote energy efficiency in a cost-effective manner.”

Efficient conversion of methane to methanol 

Methane, the primary component of natural gas, has become an increasingly important part of the global energy portfolio. However, the chemical inertness of methane and the lack of efficient methods to convert this gaseous carbon feedstock into liquid fuels has significantly limited its application. Yang Shao-Horn, the W.M. Keck Professor of Energy in the departments of Mechanical Engineering and Materials Science and Engineering, seeks to address this problem using her seed fund grant. Shao-Horn and Shuai Yuan, a postdoc in the Research Laboratory of Electronics, will focus on achieving efficient, cost-effective gas-to-liquid conversion using metal-organic frameworks (MOFs) as electrocatalysts.

Current methane activation and conversion processes are usually accomplished by costly and energy-intensive steam reforming at elevated temperature and high pressure. Shao-Horn and Yuan’s goal is to design efficient MOF-based electrocatalysts that will permit the methane-to-methanol conversion process to proceed at ambient temperature and pressure.

“If successful, this electrochemical gas-to-liquid concept could lead to a modular, efficient, and cost-effective solution that can be deployed in both large-scale industrial plants and remotely located oil fields to increase the utility of geographically isolated gas reserves,” says Shao-Horn.

Using machine learning to solve the “zeolite conundrum”

The energy field is replete with opportunities for machine learning to expedite progress toward a variety of innovative energy solutions. Rafael Gómez-Bombarelli, the Toyota Assistant Professor in Materials Processing in the Department of Materials Science and Engineering, received a grant for a project that will combine machine learning and simulation to accelerate the discovery cycle of zeolites.

Zeolites are materials with wide-ranging industrial applications as catalysts and molecular sieves because of their high stability and selective nanopores that can confine small molecules. Despite decades of abundant research, only 248 zeolite frameworks have been realized out of the millions of possible structures that have been proposed using computers — the so-called zeolite conundrum.

The problem, notes Gómez-Bombarelli, is that discovery of these new frameworks has relied mostly on trial-and-error in the lab — an approach that is both slow and labor-intensive.

In his seed grant work, Gómez-Bombarelli and his team will be using theory to speed up that process. “Using machine learning and first-principles simulations, we’ll design small molecules to dock on specific pores and direct the formation of targeted structures,” says Gómez-Bombarelli. “This computational approach will drive new synthetic outcomes in zeolites faster.”

Effective recycling of plastics

Professor Anthony Sinskey of the Department of Biology, Professor Gregory Stephanopoulos of the Department of Chemical Engineering, and graduate student Linda Zhong of biology have joined forces to address the environmental and economic problems posed by polyethylene terephthalate (PET). One of the most synthesized plastics, PET exhibits an extremely low degradation rate and its production is highly dependent on petroleum feedstocks.

“Due to the huge negative impacts of PET products, efficient recycling strategies need to be designed to decrease economic loss and adverse environmental impacts associated with single-use practices,” says Sinskey.

“PET is essentially an organic polymer of terephthalic acid and ethylene glycol, both of which can be metabolized by bacteria as energy and nutrients. These capacities exist in nature, though not together,” says Zhong. “Our goal is to engineer these metabolic pathways into E. coli to allow the bacterium to grow on PET. Using genetic engineering, we will introduce the PET-degrading enzymes into E. coli and ultimately transfer them into bioremediation organisms.”

The long-term goal of the project is to prototype a bioprocess for closed-loop PET recycling, which will decrease the volume of discarded PET products as well as the consumption of petroleum and energy for PET synthesis.

The researchers’ primary motivation in pursuing this project echoes MITEI’s overarching goal for the seed fund program: to push the boundaries of research and innovation to solve global energy and climate challenges. Zhong says, “We see a dire need for this research because our world is inundated in plastic trash. We’re only attempting to solve a tiny piece of the global problem, but we must try when much of what we hold dear depends on it.”

The MITEI Seed Fund Program has awarded new grants each year since it was established in 2008. Funding for the grants comes chiefly from MITEI’s founding and sustaining members, supplemented by gifts from generous donors. To date, MITEI has supported 177 projects with grants totaling approximately $23.6 million.

Recipients of MITEI Seed Fund grants for 2019 are:

  • “Development and prototyping of stable, safe, metal‐halogen flow batteries with high energy and power densities” — Martin Bazant of the departments of Chemical Engineering and Mathematics and T. Alan Hatton of the Department of Chemical Engineering;
  • “Silicon solar cells sensitized by exciton fission” — Marc Baldo of the Department of Electrical Engineering and Computer Science;
  • “Automatic design of structure‐directing agents for novel realizable zeolites” — Rafael Gómez‐Bombarelli of the Department of Materials Science and Engineering;
  • “Demand response, energy efficiency, and firm decisions” — Namrata Kala and Christopher Knittel of the Sloan School of Management;
  • “Direct conversion of methane to methanol by MOF‐based electrocatalysts” — Yang Shao‐Horn of the departments of Mechanical Engineering and Materials Science and Engineering;
  • “Biodegradation of plastics for efficient recycling and bioremediation” — Anthony Sinskey of the Department of Biology and Gregory Stephanopoulos of the Department of Chemical Engineering; and
  • “Asymmetric chemical doping for photocatalytic CO2 reduction” — Michael Strano of the Department of Chemical Engineering.
For Catherine Drennan, teaching and research are complementary passions

Professor of biology and chemistry is catalyzing new approaches in research and education to meet the climate challenge.

Leda Zimmerman | MIT Energy Initiative
June 26, 2019

Catherine Drennan says nothing in her job thrills her more than the process of discovery. But Drennan, a professor of biology and chemistry, is not referring to her landmark research on protein structures that could play a major role in reducing the world’s waste carbons.

“Really the most exciting thing for me is watching my students ask good questions, problem-solve, and then do something spectacular with what they’ve learned,” she says.

For Drennan, research and teaching are complementary passions, both flowing from a deep sense of “moral responsibility.” Everyone, she says, “should do something, based on their skill set, to make some kind of contribution.”

Drennan’s own research portfolio attests to this sense of mission. Since her arrival at MIT 20 years ago, she has focused on characterizing and harnessing metal-containing enzymes that catalyze complex chemical reactions, including those that break down carbon compounds.

She got her start in the field as a graduate student at the University of Michigan, where she became captivated by vitamin B12. This very large vitamin contains cobalt and is vital for amino acid metabolism, the proper formation of the spinal cord, and prevention of certain kinds of anemia. Bound to proteins in food, B12 is released during digestion.

“Back then, people were suggesting how B12-dependent enzymatic reactions worked, and I wondered how they could be right if they didn’t know what B12-dependent enzymes looked like,” she recalls. “I realized I needed to figure out how B12 is bound to protein to really understand what was going on.”

Drennan seized on X-ray crystallography as a way to visualize molecular structures. Using this technique, which involves bouncing X-ray beams off a crystallized sample of a protein of interest, she figured out how vitamin B12 is bound to a protein molecule.

“No one had previously been successful using this method to obtain a B12-bound protein structure, which turned out to be gorgeous, with a protein fold surrounding a novel configuration of the cofactor,” says Drennan.

Carbon-loving microbes show the way 

These studies of B12 led directly to Drennan’s one-carbon work. “Metallocofactors such as B12 are important not just medically, but in environmental processes,” she says. “Many microbes that live on carbon monoxide, carbon dioxide, or methane — eating carbon waste or transforming carbon — use metal-containing enzymes in their metabolic pathways, and it seemed like a natural extension to investigate them.”

Some of Drennan’s earliest work in this area, dating from the early 2000s, revealed a cluster of iron, nickel, and sulfur atoms at the center of the enzyme carbon monoxide dehydrogenase (CODH). This so-called C-cluster serves hungry microbes, allowing them to “eat” carbon monoxide and carbon dioxide.

Recent experiments by Drennan analyzing the structure of the C-cluster-containing enzyme CODH showed that in response to oxygen, it can change configurations, with sulfur, iron, and nickel atoms cartwheeling into different positions. Scientists looking for new avenues to reduce greenhouse gases took note of this discovery. CODH, suggested Drennan, might prove an effective tool for converting waste carbon dioxide into a less environmentally destructive compound, such as acetate, which might also be used for industrial purposes.

Drennan has also been investigating the biochemical pathways by which microbes break down hydrocarbon byproducts of crude oil production, such as toluene, an environmental pollutant.

“It’s really hard chemistry, but we’d like to put together a family of enzymes to work on all kinds of hydrocarbons, which would give us a lot of potential for cleaning up a range of oil spills,” she says.

The threat of climate change has increasingly galvanized Drennan’s research, propelling her toward new targets. A 2017 study she co-authored in Science detailed a previously unknown enzyme pathway in ocean microbes that leads to the production of methane, a formidable greenhouse gas: “I’m worried the ocean will make a lot more methane as the world warms,” she says.

Drennan hopes her work may soon help to reduce the planet’s greenhouse gas burden. Commercial firms have begun using the enzyme pathways that she studies, in one instance employing a proprietary microbe to capture carbon dioxide produced during steel production — before it is released into the atmosphere — and convert it into ethanol.

“Reengineering microbes so that enzymes take not just a little, but a lot of carbon dioxide out of the environment — this is an area I’m very excited about,” says Drennan.

Creating a meaningful life in the sciences 

At MIT, she has found an increasingly warm welcome for her efforts to address the climate challenge.

“There’s been a shift in the past decade or so, with more students focused on research that allows us to fuel the planet without destroying it,” she says.

In Drennan’s lab, a postdoc, Mary Andorfer, and a rising junior, Phoebe Li, are currently working to inhibit an enzyme present in an oil-consuming microbe whose unfortunate residence in refinery pipes leads to erosion and spills. “They are really excited about this research from the environmental perspective and even made a video about their microorganism,” says Drennan.

Drennan delights in this kind of enthusiasm for science. In high school, she thought chemistry was dry and dull, with no relevance to real-world problems. It wasn’t until college that she “saw chemistry as cool.”

The deeper she delved into the properties and processes of biological organisms, the more possibilities she found. X-ray crystallography offered a perfect platform for exploration. “Oh, what fun to tell the story about a three-dimensional structure — why it is interesting, what it does based on its form,” says Drennan.

The elements that excite Drennan about research in structural biology — capturing stunning images, discerning connections among biological systems, and telling stories — come into play in her teaching. In 2006, she received a $1 million grant from the Howard Hughes Medical Institute (HHMI) for her educational initiatives that use inventive visual tools to engage undergraduates in chemistry and biology. She is both an HHMI investigator and an HHMI professor, recognition of her parallel accomplishments in research and teaching, as well as a 2015 MacVicar Faculty Fellow for her sustained contribution to the education of undergraduates at MIT.

Drennan attempts to reach MIT students early. She taught introductory chemistry classes from 1999 to 2014, and in fall 2018 taught her first introductory biology class.

“I see a lot of undergraduates majoring in computer science, and I want to convince them of the value of these disciplines,” she says. “I tell them they will need chemistry and biology fundamentals to solve important problems someday.”

Drennan happily migrates among many disciplines, learning as she goes. It’s a lesson she hopes her students will absorb. “I want them to visualize the world of science and show what they can do,” she says. “Research takes you in different directions, and we need to bring the way we teach more in line with our research.”

She has high expectations for her students. “They’ll go out in the world as great teachers and researchers,” Drennan says. “But it’s most important that they be good human beings, taking care of other people, asking what they can do to make the world a better place.”

This article appears in the Spring 2019 issue of Energy Futures, the magazine of the MIT Energy Initiative. 

A chemical approach to imaging cells from the inside

Researchers develop a new microscopy system for creating maps of cells, using chemical reactions to encode spatial information.

Karen Zusi | Broad Institute
June 14, 2019

The following press release was issued today by the Broad Institute of MIT and Harvard.

A team of researchers at the McGovern Institute and Broad Institute of MIT and Harvard has developed a new technique for mapping cells. The approach, called DNA microscopy, shows how biomolecules such as DNA and RNA are organized in cells and tissues, revealing spatial and molecular information that is not easily accessible through other microscopy methods. DNA microscopy also does not require specialized equipment, enabling large numbers of samples to be processed simultaneously.

“DNA microscopy is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen,” says first author Joshua Weinstein, a postdoctoral associate at the Broad Institute. “It will allow us to see how genetically unique cells — those comprising the immune system, cancer, or the gut, for instance — interact with one another and give rise to complex multicellular life.”

The new technique is described in Cell. Aviv Regev, core institute member and director of the Klarman Cell Observatory at the Broad Institute and professor of biology at MIT, and Feng Zhang, core institute member of the Broad Institute, investigator at the McGovern Institute for Brain Research at MIT, and the James and Patricia Poitras Professor of Neuroscience at MIT, are co-authors. Regev and Zhang are also Howard Hughes Medical Institute Investigators.

The evolution of biological imaging

In recent decades, researchers have developed tools to collect molecular information from tissue samples, data that cannot be captured by either light or electron microscopes. However, attempts to couple this molecular information with spatial data — to see how it is naturally arranged in a sample — are often machinery-intensive, with limited scalability.

DNA microscopy takes a new approach to combining molecular information with spatial data, using DNA itself as a tool.

To visualize a tissue sample, researchers first add small synthetic DNA tags, which latch on to molecules of genetic material inside cells. The tags are then replicated, diffusing in “clouds” across cells and chemically reacting with each other, further combining and creating more unique DNA labels. The labeled biomolecules are collected, sequenced, and computationally decoded to reconstruct their relative positions and a physical image of the sample.

The interactions between these DNA tags enable researchers to calculate the locations of the different molecules — somewhat analogous to cell phone towers triangulating the locations of different cell phones in their vicinity. Because the process only requires standard lab tools, it is efficient and scalable.

In this study, the authors demonstrate the ability to molecularly map the locations of individual human cancer cells in a sample by tagging RNA molecules. DNA microscopy could be used to map any group of molecules that will interact with the synthetic DNA tags, including cellular genomes, RNA, or proteins with DNA-labeled antibodies, according to the team.

“DNA microscopy gives us microscopic information without a microscope-defined coordinate system,” says Weinstein. “We’ve used DNA in a way that’s mathematically similar to photons in light microscopy. This allows us to visualize biology as cells see it and not as the human eye does. We’re excited to use this tool in expanding our understanding of genetic and molecular complexity.”

Funding for this study was provided by the Simons Foundation, Klarman Cell Observatory, NIH (R01HG009276, 1R01- HG009761, 1R01- MH110049, and 1DP1-HL141201), New York Stem Cell Foundation, Simons Foundation, Paul G. Allen Family Foundation, Vallee Foundation, the Poitras Center for Affective Disorders Research at MIT, the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, J. and P. Poitras, and R. Metcalfe. 

The authors have applied for a patent on this technology.

From one MSRP generation to the next

Squire Booker PhD ’94 met with former and current Summer Research Program students to explain how his summer experience at MIT shaped his research trajectory.

Raleigh McElvery | Department of Biology
June 11, 2019

On June 5, 20 students from the 2019 MIT Summer Research Program (MSRP) cohort and eight program alumni had the chance to meet Squire Booker PhD ’94. Booker was the keynote speaker at MIT’s Investiture of Doctoral Hoods and Degree Conferral Ceremony, which took place on June 6. He is also an MSRP alumnus from the very first cohort, and conducted his PhD work in the Department of Chemistry under the direction of JoAnne Stubbe.

He recounted how his MSRP experience changed his career path. “I discovered my passion for research that summer,” he said.

Today, Booker is the Evan Pugh Professor of chemistry, biochemistry, and molecular biology, and the Eberly Family Distinguished Chair in Science at Pennsylvania State University. He is also an investigator with the Howard Hughes Medical Institute, and was recently elected to the National Academy of Sciences.

The lunch was organized by Catherine Drennan, an MIT professor of biology and chemistry and a Howard Hughes Medical Institute Investigator.

“When I found out that Professor Booker was selected to speak at the MIT hooding ceremony, I knew that I wanted to arrange for him to meet with current and recent MSRP students,” she says. “It means a lot to meet someone successful who was once in your shoes.”

Stephanie Guerra, an undergraduate at the University of Puerto Rico at Humacao who will be working in the Laub lab this summer, says it was inspiring to meet someone whose career trajectory had been so impacted by the MSRP experience. “It resonated with me when he mentioned that we shouldn’t question the opportunities we get,” she says. “We should be grateful for them and make the best of them.”

These sentiments were echoed by Sofía Hernández Torres from the University of Puerto Rico at Mayagüez, who will be working in the Calo lab. “He is an accomplished man with very entertaining charisma,” she says. “I was motivated to continue to fight for a successful science career, where you are able to choose where you go next instead of having to follow a path defined by others.”

MSRP is a research-intensive summer training program for non-MIT sophomore and junior science majors who have an interest in a research career. Since 2003, it has been divided into two branches: MSRP General and MSRP-Bio. The latter offers a 10-week practical training in one of over 90 research laboratories affiliated with the departments of Biology, Brain and Cognitive Sciences, or Biological Engineering, and features weekly academic seminars, meetings with faculty, and many extracurricular activities.

At doctoral ceremony, a strong call to provide opportunity for all

Biochemist Squire Booker PhD ’94 says MIT’s new doctoral graduates will “grow as future leaders” by giving back.

Peter Dizikes | MIT News Office
June 7, 2019

Distinguished biochemist Squire Booker PhD ’94 emphasized the importance of opportunity for all, in his keynote speech at today’s 2019 Investiture of Doctoral Hoods and Degree Conferral, a ceremony for MIT’s new doctoral degree holders.

While congratulating MIT’s doctoral graduates, Booker also urged them to give back to society and to take responsibility for helping others accomplish their own goals — however daunting those goals, such as a PhD, may seem.

“Almost anyone can excel if given the chance,” Booker said. “Take advantage of opportunities, and make the most of them. But also, work to provide opportunities for others. That’s how you will grow as a future leader.”

Reflecting on his own trajectory, from a childhood when he knew no one working in the sciences to a career on the front lines of discovery, Booker called himself “just an average guy from southeast Texas, no different than anyone else.” But he said new opportunities had “made all the difference” in his career. One key moment of opportunity, Booker said, was his graduate training at the Institute.

“MIT gave me my first real opportunity to explore scientific research and realize my passion for discovery and working with people from all over the world to solve problems,” Booker said. He credited his mentors with “helping me to achieve goals that I didn’t even know existed when I undertook this journey, or that I didn’t even have for myself. I can honestly say my cup runneth over today.”

Booker is the Evan Pugh Professor of chemistry and of biochemistry and molecular biology and Eberly Family Distinguished Chair in Science at Penn State University. He is also an investigator with the Howard Hughes Medical Institute, and in April of this year was elected to the National Academy of Sciences.

During his career, Booker has conducted significant research uncovering the ways enzymes catalyze reactions within cells, a line of work with applications ranging from medicine to biofuels.

The ceremony honors graduate students who have earned their doctoral degrees within this academic year. It was held this year in MIT’s Killian Court, where a large audience of family members and friends filled the seats. Killian Court is also the site of Friday’s 2019 Commencement exercises.

Graduates from 26 departments, programs, and centers at the Institute, as well as MIT’s joint program with the Woods Hole Oceanographic Institution, received degrees on Thursday. MIT faculty — who wear the brightly colored formal garb of the universities where they received their own doctorates — placed doctoral hoods, a part of the formal academic clothing, over the shoulders of the new graduates.

In his remarks, Booker said he shared the experience this year’s doctoral graduates have gone through, and understood how hard they have worked at the Institute.

“I don’t just imagine the blood, the sweat, the tears, and the immense amount of time that you put into arriving at this point in your careers and your lives,” Booker said. “I actually experienced it firsthand as a graduate student here at MIT between 1987 and 1994.” He cited his graduate advisor, JoAnne Stubbe, as an important influence on his career.

Booker infused his remarks with self-deprecating humor, joking that he first thought MIT had ask him to speak by mistake. But he also spoke earnestly about the serious hurdles he had faced in his life.

Booker grew up in what he described as a segregated environment in Beaumont, Texas. He noted that it was not uncommon for him to hear teachers make disparaging remarks about the abilities of African-Americans, adding, “A career in science was about as likely as winning the lottery … largely because there were no role models.”

Raised by a grandmother with the help of three uncles, Booker earned his undergraduate degree in chemistry at Austin College in Sherman, Texas, and first came to MIT in 1986, as part of the Institute’s MIT Summer Research Program, which now supports 40 interns every year from underrepresented backgrounds.

That stint at MIT helped lead Booker to enter the graduate program, where he studied biochemistry. It also gave him a greater awareness of the travails of black scientists who had gone before him — partly through the work of MIT’s Kenneth Manning, the Thomas Maloy Professor in Rhetoric, whose 1983 book, “Black Apollo of Science: The Life of Ernest Everett Just,” chronicled the life of a pioneering black researcher excluded from American academia.

In his speech, Booker outlined the lives of both Just and Percy Lavon Julian, an innovative 20th-century African-American research chemist who also spent decades excluded from a conventional professorship in academia.

“We’re still trying to recover from the bigotry and misogyny of the past, some of which still exist,” Booker said. In that vein, he noted, in 2008, he became the first Afrcian-American professor in Penn State’s chemistry department.

‘That it took so long is completely tragic,” said Booker, observing that countless talented people had been excluded from promising careers and fulfilling lives as a result of prejudice.

“America’s strength is its people,” Booker said. “And there is so much untapped potential in people who have been traditionally disenfranchised, including people of color, women, the LGBTQ community, and the differently abled.”

At the same time, Booker added, “In fact, first-generation white students, or students from modest socioeconomic backgrounds, are the ones that I have impacted the greatest, directly, at Penn State. And you can’t imagine how appreciative they have been to have been given the chance, and some direction.”

Booker was introduced by MIT Chancellor Cynthia Barnhart SM ’86, PhD ’88, the Ford Foundation Professor of Engineering, who briefly delivered her own remarks to the graduates.

“Today is about honoring the accomplishment and success of all of you, our doctoral candidates,” Barnhart said. “Congratulations. Each and every one of you have succeeded. … You were curious and creative, determined to problem-solve, to collaborate, and to innovate.”

Barnhart also called the doctoral hooding ceremony a “delightfully hopeful moment where infinite possibilities stretch out in front of you,” and asked the graduates to rise in appreciation of their friends and families who have supported their efforts.

This is the fifth year in a row that MIT’s doctoral hooding ceremony has had a keynote speaker — who is annually drawn from the ranks of past MIT doctoral graduates. Booker was chosen with input from the MIT community.

The festive, bright regalia of the doctoral ceremony represents a mix of old traditions and recent changes. Formal academic wear, at least of the kind seen at commencement ceremonies, dates to the 1400s, if not earlier. However, American universities did not agree to standards for such gowns and hoods until 1893.

At MIT, the doctoral degree robes were redesigned as recently as 1995. MIT gowns feature a silver-gray robe with a cardinal red velvet front panel, and are embellished by cardinal red velvet bars on the sleeves. Additional color markings signify whether graduates have received the Doctor of Philosophy degree (PhD) or the Doctor of Science degree (ScD). Silver-gray academic caps complement the gowns. The doctoral hoods are an accessory to the main robe ensemble.

After Barnhart’s introductory remarks and Booker’s speech, all doctoral graduates had their names announced as they walked across the stage one by one. The newly minted degree holders then had the hoods draped over their shoulders by their department or program heads.

The names of all the new doctoral degree holders were read aloud, one after another, by two MIT staff members: Monica Lee, a senior communications officer in the Department of Facilities; and Steven M. Lanou, a project manager in the Office of Sustainability.

Drug makes tumors more susceptible to chemo

Compound that knocks out a DNA repair pathway enhances cisplatin treatment and helps prevent drug-resistance.

Anne Trafton | MIT News Office
June 6, 2019

Many chemotherapy drugs kill cancer cells by severely damaging their DNA. However, some tumors can withstand this damage by relying on a DNA repair pathway that not only allows them to survive, but also introduces mutations that helps cells become resistant to future treatment.

Researchers at MIT and Duke University have now discovered a potential drug compound that can block this repair pathway. “This compound increased cell killing with cisplatin and prevented mutagenesis, which is was what we expected from blocking this pathway,” says Graham Walker, the American Cancer Society Research Professor of Biology at MIT, a Howard Hughes Medical Institute Professor, and one of the senior authors of the study.

When they treated mice with this compound along with cisplatin, a DNA-damaging drug, tumors shrank much more than those treated with cisplatin alone. Tumors treated with this combination would be expected not to develop new mutations that could make them drug-resistant.

Cisplatin, which is used as the first treatment option for at least a dozen types of cancer, often successfully destroys tumors, but they frequently grow back following treatment. Drugs that target the mutagenic DNA repair pathway that contributes to this recurrence could help to improve the long-term effectiveness of not only cisplatin but also other chemotherapy drugs that damage DNA, the researchers say.

“We’re trying to make the therapy work better, and we also want to make the tumor recurrently sensitive to therapy upon repeated doses,” says Michael Hemann, an associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the study.

Pei Zhou, a professor of biochemistry at Duke University, and Jiyong Hong, a professor of chemistry at Duke, are also senior authors of the paper, which appears in the June 6 issue of Cell. The lead authors of the paper are former Duke graduate student Jessica Wojtaszek, MIT postdoc Nimrat Chatterjee, and Duke research assistant Javaria Najeeb.

Overcoming resistance

Healthy cells have several repair pathways that can accurately remove DNA damage from cells. As cells become cancerous, they sometimes lose one of these accurate DNA repair systems, so they rely heavily on an alternative coping strategy known as translesion synthesis (TLS).

This process, which Walker has been studying in a variety of organisms for many years, relies on specialized TLS DNA polymerases. Unlike the normal DNA polymerases used to replicate DNA, these TLS DNA polymerases can essentially copy over damaged DNA, but the copying they perform is not very accurate. This enables cancer cells to survive treatment with a DNA-damaging agent such as cisplatin, and it leads them to acquire many additional mutations that can make them resistant to further treatment.

“Because these TLS DNA polymerases are really error-prone, they are accountable for nearly all of the mutation that is induced by drugs like cisplatin,” Hemann says. “It’s very well-established that with these frontline chemotherapies that we use, if they don’t cure you, they make you worse.”

One of the key TLS DNA polymerases required for translesion synthesis is Rev1, and its primary function is to recruit a second TLS DNA polymerase that consists of a complex of the Rev3 and Rev7 proteins. Walker and Hemann have been searching for ways to disrupt this interaction, in hopes of derailing the repair process.

In a pair of studies published in 2010, the researchers showed that if they used RNA interference to reduce the expression of Rev1, cisplatin treatment became much more effective against lymphoma and lung cancer in mice. While some of the tumors grew back, the new tumors were not resistant to cisplatin and could be killed again with a new round of treatment.

After showing that interfering with translesion synthesis could be beneficial, the researchers set out to find a small-molecule drug that could have the same effect. Led by Zhou, the researchers performed a screen of about 10,000 potential drug compounds and identified one that binds tightly to Rev1, preventing it from interacting with Rev3/Rev7 complex.

The interaction of Rev1 with the Rev7 component of the second TLS DNA polymerase had been considered “undruggable” because it occurs in a very shallow pocket of Rev1, with few features that would be easy for a drug to latch onto. However, to the researchers’ surprise, they found a molecule that actually binds to two molecules of Rev1, one at each end, and brings them together to form a complex called a dimer. This dimerized form of Rev1 cannot bind to the Rev3/Rev7 TLS DNA polymerase, so translesion synthesis cannot occur.

Chatterjee tested the compound along with cisplatin in several types of human cancer cells and found that the combination killed many more cells than cisplatin on its own. And, the cells that survived had a greatly reduced ability to generate new mutations.

“Because this novel translesion synthesis inhibitor targets the mutagenic ability of cancer cells to resist therapy, it can potentially address the issue of cancer relapse, where cancers continue to evolve from new mutations and together pose a major challenge in cancer treatment,” Chatterjee says.

A powerful combination

Chatterjee then tested the drug combination in mice with human melanoma tumors and found that the tumors shrank much more than tumors treated with cisplatin alone. They now hope that their findings will lead to further research on compounds that could act as translesion synthesis inhibitors to enhance the killing effects of existing chemotherapy drugs.

Zhou’s lab at Duke is working on developing variants of the compound that could be developed for possible testing in human patients. Meanwhile, Walker and Hemann are further investigating how the drug compound works, which they believe could help to determine the best way to use it.

“That’s a future major objective, to identify in which context this combination therapy is going to work particularly well,” Hemann says. “We would hope that our understanding of how these are working and when they’re working will coincide with the clinical development of these compounds, so by the time they’re used, we’ll understand which patients they should be given to.”

The research was funded, in part, by an Outstanding Investigator Award from the National Institute of Environmental Health Sciences to Walker, and by grants from the National Cancer Institute, the Stewart Trust, and the Center for Precision Cancer Medicine at MIT.

Merging machine learning and the life sciences

Through computing, senior and Marshall Scholar Anna Sappington seeks answers to biological questions.

Gina Vitale | MIT News correspondent
May 22, 2019

Anna Sappington’s first moments of fame came when she was a young girl, living in a home so full of pets she calls it a zoo. She grew up on the Chesapeake Bay, surrounded by a lush environment teeming with wildlife, and her father was an environmental scientist. One day, when she found a frog in a skip laurel bush, she named him Skippy and built him a habitat. Later on, she and Skippy appeared on the Animal Planet TV special “What’s to Love About Weird Pets?”

Now a senior majoring in computer science and molecular biology, Sappington has been chosen for another prestigious honor: She’s one of five MIT students selected this year to be Marshall Scholars. She chose to study computer science because she wanted to have a role in pulling apart and understanding data, and she chose biology because of her lifelong fascination with nature, cells, genetic inheritance — and, of course, Skippy.

“My interests have grown and expanded in different ways, but they’re still kind of rooted in this natural dual passion that I have for both of these fields,” she says.

An eye for genomic research

When Sappington came to MIT, it was right after her first summer internship at the National Institutes of Health, where she examined genes that could be related to increased risk of cardiovascular disease. It was her first experience working with data on human patients, and it inspired her to continue working in medical research.

When she was a first-year student, Sappington spent the year at the Koch Institute, working with a graduate student to determine how liver cells respond to infection by hepatitis B virus. The summer after that, she went back to the NIH to contribute to a different project. This one still involved human health data, but it was more focused on building a computational tool. Sappington helped develop an algorithm that would quickly calculate how similar two genomes or proteins were to each other, a technology that could be used to screen for different bacteria strains in real-time.

“I wanted to kind of get my feet wet in all the different kinds of ways computer science and biology and human health can interact,” she says.

Since her return from the NIH at the beginning of her sophomore year, Sappington has been working in Aviv Regev’s lab in the Broad Institute of MIT and Harvard. She says Regev, a professor in the MIT Department of Biology, has been nothing short of an inspiration.

“She herself is just an incredible role model for the world of computational biology,” Sappington says.

The main initiative of Regev’s lab is an initiative called the Human Cell Atlas, which was recently named Science’s Breakthrough of the Year. It’s like a layer on top of the Human Genome Project, she says. They are working to identify and catalogue the different types of cells, such as skin cells and lung cells. The need for the cataloging comes from the fact that even though these cells have the exact same DNA genome, they have different specialized functions, and therefore can’t be identified by genome alone.

“Within a given tissue, like your skin tissue, cells are actually like a whole collage of different molecular profiles in how they express their genes,” she says. “So while the underlying genome is the same, there’s all sorts of other factors that make your cells express those genes — which turn into proteins — differently.”

Because the human body contains so many different types of cells, teams of researchers work on different pieces. Sappington works on data analysis as part of a team that is classifying retinal cells. It’s a unique challenge, she says, because the retina has more than 40 different types of cells, all of which respond to disease in different ways. While still chipping away at human retinal cell types, her team contributed to a recently published retinal cell atlas for the macaque monkey. For her undergraduate research career, Sappington was named a 2018-2019 Goldwater Scholar.

Dancing, speaking, leading

Before coming to MIT, Sappington had never been involved in dancing. But after she saw a showcase by the Asian Dance Team her first year, she decided to give it a try. After a few semesters dancing with ADT, Sappington also joined MIT DanceTroupe, where she found the culture to be creative, supportive, and incredibly fun.

“[I] just really fell in love with the community, and the general community of dancers at MIT,” she says.

Dance wasn’t the only aspect of the arts and humanities at MIT that she loved. She is also a part of the Burchard Scholars program, which allows students with a particular interest in the humanities to explore that topic. After she took a linguistics class with Professor David Pesetsky her first year, that field became her official humanities concentration. She ended up taking the next level of that class, which centered around syntax, and then she and five other students later created their own special subject class on linguistics.

“Essentially linguistics is the study of how language as a whole works, and the underlying rules that govern it,” she says. “It interfaces with brain and cognitive science, and even computer science, and how language is learned and acquired.”

Outside of class, Sappington has also been involved with TechX, a student-run organization that is responsible for many of MIT’s tech-related events, including HackMIT. Events also include the makeathon MakeMIT, the spring career fair and technology demo xFair, and high school mentoring program THINK. After serving on and running an event committee, Sappington served as the overall director for TechX in her junior year. While she’s no longer in charge, she’s still grateful to be part of the team.

“The whole thing was like one big family. … Each committee has its own intercommittee pride with the event that they run, but then everyone also has to rely on each other,” she says.

Machine learning across the pond

After graduation, Sappington will be heading off to University College London to earn her MS in machine learning. Her goal is to explore machine learning in a context that isn’t biology, so that she can learn new and different approaches that she might later be able to apply to biological challenges. The second year of her Marshall Scholarship will be spent at Cambridge University, where she will do a full year of research, likely involving machine learning applied to health care or other biological questions.

Her ultimate goal is to find new and better ways to use machine learning and technology to improve the health care system. To that end, she aims to get her MD/PhD after the next two years in England. After volunteering at the Massachusetts General Hospital and shadowing doctors in the Boston area, Sappington is pretty certain she wants a career where she can interact with patients while still being involved with computer science and biology. She’s excited to move forward with the next chapter of her life — but when it comes to leaving MIT, she’s got understandably mixed feelings.

“I think no matter where I would be going after graduation, it’s bittersweet to leave the incredible community that is the MIT community,” she says.

Eleven MIT students accept 2019 Fulbright Fellowships

Grantees will spend the 2019-2020 academic year pursuing research and teaching opportunities abroad.

Julia Mongo | Office of Distinguished Fellowships
May 17, 2019

Eleven MIT graduating seniors and current graduate students have been named winners in the 2019-2020 Fulbright U.S. Student Fellowship Program. In addition to the 11 students accepting their awards, three applicants from MIT were selected as finalists but decided to decline their grants.

MIT’s newest Fulbright Students will engage in independent research and English teaching assignments in Brazil, the Netherlands, Spain, Russia, Taiwan, and Senegal.

Sponsored by the U.S. Department of State’s Bureau of Educational and Cultural Affairs, the mission of Fulbright is to promote cultural exchange, increase mutual understanding, and build lasting relationships among people of the world. The Fulbright U.S. Student Program offers grants in over 140 countries.

The MIT students were supported in the application process by the Presidential Committee on Distinguished Fellowships, chaired by professors Rebecca Saxe and Will Broadhead, and by MIT’s Distinguished Fellowships Office within Career Advising and Professional Development. The MIT winners are:

Annamarie “Anna” Bair ’18 earned a bachelor of science in computer science and engineering in June 2018 and will receive her master of engineering degree in computer science later this year. In Barcelona, Spain, Bair will engage in complex systems research.

Abigail “Abby” Bertics will graduate in June with a bachelor of science in electrical engineering and computer science. Her research in Yekaterinburg, Russia, will focus on natural language processing methods for understanding English second language acquisition by Russian speakers.

Hope Chen is a senior graduating with a bachelor of science in mechanical engineering. She will be going to Taiwan as an English Teaching Assistant in primary school classrooms. After completing her Fulbright program and returning to the U.S., Chen will matriculate in medical school.

Alexis D’Alessandro will graduate this spring with a bachelor of science in mechanical engineering. For her research in Aracaju, Brazil, she will develop an educational program and chemical sensing tool to promote water safety awareness among children.

Sarah DiIorio will earn her bachelor of science in biological engineering in June. She is headed to Eindhoven, the Netherlands, to conduct medical research related to cartilage regeneration for osteoarthritis.

Katie Fisher is a senior in MIT’s Scheller Teaching Education Program graduating with a bachelor of science in urban studies and planning with a concentration in education. As an English teaching assistant in the Netherlands, Fisher will work with students at a vocational college in Amsterdam.

Miranda McClellan ’18 received a bachelor of science in computer science and engineering in June 2018 and will earn her master of engineering degree in computer science this spring. McClellan will research automated scaling of 5G computer network resources in Barcelona, Spain.

Samira Okudo will graduate in June with a joint bachelor of science in computer science and comparative media studies. As an English teaching assistant in Brazil, she will work with university students training to be English-language instructors.

James Pelletier is a PhD candidate in physics. For his Fulbright research in Madrid, Spain, he will develop biophysical models to investigate how plants process information for cellular resource allocation and agricultural efficiency.

Jonars Spielberg is a third-year doctoral student in the Department of Urban Studies and Planning’s international development program. In Senegal, he will examine how the personal interactions of bureaucrats and farmers shape agricultural policy implementation in the country’s main irrigated regions.

Catherine Wu will graduate in June with a bachelor of science in biology. She will be working with university students in Brazil as a Fulbright English Teaching Assistant.

MIT students interested in applying to the Fulbright U.S. Student Program should contact Julia Mongo in Distinguished Fellowships.

Measuring chromosome imbalance could clarify cancer prognosis

A study of prostate cancer finds “aneuploid” tumors are more likely to be lethal than tumors with normal chromosome numbers.

Anne Trafton | MIT News Office
May 13, 2019

Most human cells have 23 pairs of chromosomes. Any deviation from this number can be fatal for cells, and several genetic disorders, such as Down syndrome, are caused by abnormal numbers of chromosomes.

For decades, biologists have also known that cancer cells often have too few or too many copies of some chromosomes, a state known as aneuploidy. In a new study of prostate cancer, researchers have found that higher levels of aneuploidy lead to much greater lethality risk among patients.

The findings suggest a possible way to more accurately predict patients’ prognosis, and could be used to alert doctors which patients might need to be treated more aggressively, says Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research in the Department of Biology and a member of the Koch Institute for Integrative Cancer Research.

“To me, the exciting opportunity here is the ability to inform treatment, because prostate cancer is such a prevalent cancer,” says Amon, who co-led this study with Lorelei Mucci, an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health.

Konrad Stopsack, a research associate at Memorial Sloan Kettering Cancer Center, is the lead author of the paper, which appears in the Proceedings of the National Academy of Sciences the week of May 13. Charles Whittaker, a Koch Institute research scientist; Travis Gerke, a member of the Moffitt Cancer Center; Massimo Loda, chair of pathology and laboratory medicine at New York Presbyterian/Weill Cornell Medicine; and Philip Kantoff, chair of medicine at Memorial Sloan Kettering; are also authors of the study.

Better predictions

Aneuploidy occurs when cells make errors sorting their chromosomes during cell division. When aneuploidy occurs in embryonic cells, it is almost always fatal to the organism. For human embryos, extra copies of any chromosome are lethal, with the exceptions of chromosome 21, which produces Down syndrome; chromosomes 13 and 18, which lead to developmental disorders known as Patau and Edwards syndromes; and the X and Y sex chromosomes. Extra copies of the sex chromosomes can cause various disorders but are not usually lethal.

Most cancers also show very high prevalence of aneuploidy, which poses a paradox: Why does aneuploidy impair normal cells’ ability to survive, while aneuploid tumor cells are able to grow uncontrollably? There is evidence that aneuploidy makes cancer cells more aggressive, but it has been difficult to definitively demonstrate that link because in most types of cancer nearly all tumors are aneuploid, making it difficult to perform comparisons.

Prostate cancer is an ideal model to explore the link between aneuploidy and cancer aggressiveness, Amon says, because, unlike most other solid tumors, many prostate cancers (25 percent) are not aneuploid or have only a few altered chromosomes. This allows researchers to more easily assess the impact of aneuploidy on cancer progression.

What made the study possible was a collection of prostate tumor samples from the Health Professionals Follow-up Study and Physicians’ Health Study, run by the Harvard T.H. Chan School of Public Health over the course of more than 30 years. The researchers had genetic sequencing information for these samples, as well as data on whether and when their prostate cancer had spread to other organs and whether they had died from the disease.

Led by Stopsack, the researchers came up with a way to calculate the degree of aneuploidy of each sample, by comparing the genetic sequences of those samples with aneuploidy data from prostate genomes in The Cancer Genome Atlas. They could then correlate aneuploidy with patient outcomes, and they found that patients with a higher degree of aneuploidy were five times more likely to die from the disease. This was true even after accounting for differences in Gleason score, a measure of how much the patient’s cells resemble cancer cells or normal cells under a microscope, which is currently used by doctors to determine severity of disease.

The findings suggest that measuring aneuploidy could offer additional information for doctors who are deciding how to treat patients with prostate cancer, Amon says.

“Prostate cancer is terribly overdiagnosed and terribly overtreated,” she says. “So many people have radical prostatectomies, which has significant impact on people’s lives. On the other hand, thousands of men die from prostate cancer every year. Assessing aneuploidy could be an additional way of helping to inform risk stratification and treatment, especially among people who have tumors with high Gleason scores and are therefore at higher risk of dying from their cancer.”

“When you’re looking for prognostic factors, you want to find something that goes beyond known factors like Gleason score and PSA [prostate-specific antigen],” says Bruce Trock, a professor of urology at Johns Hopkins School of Medicine, who was not involved in the research. “If this kind of test could be done right after a prostatectomy, it could give physicians information to help them decide what might be the best treatment course.”

Amon is now working with researchers from the Harvard T.H. Chan School of Public Health to explore whether aneuploidy can be reliably measured from small biopsy samples.

Aneuploidy and cancer aggressiveness

The researchers found that the chromosomes that are most commonly aneuploid in prostate tumors are chromosomes 7 and 8. They are now trying to identify specific genes located on those chromosomes that might help cancer cells to survive and spread, and they are also studying why some prostate cancers have higher levels of aneuploidy than others.

“This research highlights the strengths of interdisciplinary, team science approaches to tackle outstanding questions in prostate cancer,” Mucci says. “We plan to translate these findings clinically in prostate biopsy specimens and experimentally to understand why aneuploidy occurs in prostate tumors.”

Another type of cancer where most patients have low levels of aneuploidy is thyroid cancer, so Amon now hopes to study whether thyroid cancer patients with higher levels of aneuploidy also have higher death rates.

“A very small proportion of thyroid tumors is highly aggressive and lethal, and I’m starting to wonder whether those are the ones that have some aneuploidy,” she says.

The research was funded by the Koch Institute Dana Farber/Harvard Cancer Center Bridge Project and by the National Institutes of Health, including the Koch Institute Support (core) Grant.