#broad institute

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Student spotlight: Victory Yinka-Banjo

This interview is part of a series from the MIT Department of Electrical Engineering and Computer Science featuring students answering questions about themselves and life at the Institute. Today’s interviewee, Victory Yinka-Banjo, is a junior majoring in MIT Course 6-7: Computer Science and Molecular Biology. Yinka-Banjo keeps a packed schedule: She is a member of the Office of Minority Education (OME) Laureates and Leaders program; a 2024 fellow in the public service-oriented BCAP program; has previously served as secretary of the African Students’ Association, and is now undergraduate president of the MIT Biotech Group; additionally, she is a SuperUROP Scholar; a member of the Ginkgo Bioworks’ Cultivate Fellowship (a program that supports students interested in synthetic biology/biotech); and an ambassador for Leadership Brainery, which equips juniors/leaders of color with the resources needed to prepare for graduate school. She recently found time to share a peek into her MIT experience.

Q: What’s your favorite building or room within MIT?

A: It has to be the Broad Institute of MIT and Harvard on Ames Street in Kendall Square, where I do my SuperUROP research in Caroline Uhler’s lab. Outside of classes, you’re 90 percent likely to find me on the newest mezzanine floor (between the 11th and 12th floor), in one of the UROP [Undergraduate Research Opportunities Program] rooms I share with two other undergrads in the lab. We have standing desks, an amazing coffee/hot chocolate machine, external personal monitors, comfortable sofas — everything, really! Not only is it my favorite building, it is also my favorite study spot on campus. In fact, I am there so often that when friends recently planned a birthday surprise for me, they told me they were considering having it at the Broad, since they could count on me being there. 

I think the most beautiful thing about this building, apart from the beautiful view of Cambridge we get from being on one of the highest floors, is that when I was applying to MIT from high school, I had fantasized working at the Broad because of the groundbreaking research. To think that it is now a reality makes me appreciate every minute I spend on my floor, whether I am doing actual research or some last-minute studying for a midterm. 

Q: Tell me about one interest or hobby you’ve discovered since you came to MIT.

A: I have become pretty involved in the performing arts since I got to MIT! I have acted in two plays run by the Black Theater Guild, which was revived during my freshman year by one of my friends. I played a supporting role in the first play called “Nkrumah’s Last Day,” which was about Ghana at a time of governance under Kwame Nkrumah, its first president. In the second play, a ghost story/comedy called “Shooting the Sheriff,” I played one of the lead roles. Both caused me to step way out of my comfort zone and I loved the experiences because of that. I also got to act with some of my close friends who were first-time stage actors as well, so that made it even more fun. 

Outside of acting, I also do spoken word/poetry. I have performed at events like the African Students Association Cultural Night, MIT Africa Innovate Conference, and Black Women’s Alliance Banquet. I try to use my pieces to share my experiences both within and beyond MIT, offering the perspective of an international Nigerian student. My favorite piece was called “Code Switch,” and I used concepts from [computer science] and biology (especially genetic code switching), to draw parallels with linguistic code-switching, and emphasize the beauty and originality of authenticity. This semester, I’m also a part of MIT Monologues and will be performing a piece called “Inheritance,” about the beauty of self-love found in affection transferred from a mother. 

Q: Are you a re-reader or a re-watcher — and if so, what are your comfort books, shows, or movies?

A: I don’t watch too many movies, although I used to be obsessed with all parts of “High School Musical;” and the only book I’ve ever reread is “Americanah.” I would actually say I am a re-podcaster! My go-to comfort-podcast is this episode, “A Breakthrough Unfolds”, by Google DeepMind. It makes me a little emotional every time I listen. It is such an exemplification of the power of science and its ability to break boundaries that humans formerly thought impossible. As a computer science and biology major, I am particularly interested in these two disciplines’ applications to relevant problems, like the protein-folding problem discussed in the episode, which DeepMind’s solution for has caused massive advances in the biotech industry. It makes me so hopeful for the future of biology, and the ways in which computation can advance human health and precision medicine.

Q: Who’s your favorite artist?

A: When I think of the word ‘artist,’ I think of music artists first. There are so many who I love; my favorites also evolve over time. I’m Christian, so I listen to a lot of gospel music. I’m also Nigerian so I listen to a lot of Afrobeats. Since last summer, I’ve been obsessed with Limoblaze, who fuses both gospel and Afrobeats music! KB, a super talented gospel rapper, is also somewhat tied in ranking with Limo for me right now. His songs are probably ~50 percent of my workout playlist.

Q: It’s time to get on the shuttle to the first Mars colony, and you can only bring one personal item. What are you going to bring?

A: Oooh, this is a tough one, but it has to be my Brass Rat. Ever since I got mine at the end of sophomore year, it’s been nearly impossible for me to take it off. If there’s ever a time I forget to wear it, my finger feels off for the entire day. 

Q: Tell me about one conversation that changed the trajectory of your life.

A: Two specific career-defining moments come to mind. They aren’t quite conversations, but they are talks/lectures that I was deeply inspired by. The first was towards the end of high school when I watched this TEDx Talk about storing data in DNA. At the time, I was getting ready to apply to colleges and I knew that biology and computer science were two things I really liked, but I didn’t really understand the possibilities that could be birthed from them coming together as an interdisciplinary field. The TEDx talk was my eureka moment for computational biology. 

The second moment was in my junior fall during an introductory lecture to “Lab Fundamentals for Bioengineering,” by Professor Jacquin Niles. I started the school year with a lot of confusion about my future post-grad, and the relevance of my planned career path to the communities that I care about. Basically, I was unsure about how computational biology fit into the context of Nigeria’s problems, especially because my interest in the field is oriented towards molecular biology/medicine, not necessarily public health. 

In the U.S., most research focuses on diseases like cancer and Alzheimer’s, which, while important, are not the most pressing health conditions in tropical regions like Nigeria. When Professor Niles told us about his lab’s dedication to malaria research from a molecular biology standpoint, it was yet another eureka moment. Like, Yes! Computation and molecular biology can indeed mitigate diseases that affect developing nations like Nigeria — diseases that are understudied, and whose research is underfunded. 

Since his talk, I found a renewed sense of purpose. Grad school isn’t the end goal. Using my skills to shine a light on the issues affecting my people that deserve far more attention is the goal. I’m so excited to see how I will use computational biology to possibly create the next cure to a commonly neglected tropical disease, or accelerate the diagnosis of one. Whatever it may be, I know that it will be close to home, eventually.

Q: What are you looking forward to about life after graduation? What do you think you’ll miss about MIT?

A: Thinking about graduating actually makes me sad. I’ve grown to love MIT. The biggest thing I’ll miss, though, is Independent Activities Period (IAP). It is such a unique part of the MIT experience. I’ve done a web development class/competition, research, a data science challenge, a molecular bio crash course, and a deep learning crash course over the past three IAPs. It is such an amazing time to try something low stakes, forget about grades, explore Boston, build a robot, travel abroad, do less, go slower, really rejuvenate before the spring, and embrace MIT’s motto of “mind and hand” by just being creative and explorative. It is such an exemplification of what it means to go here, and I can’t imagine it being the same anywhere else. 

That said, I look forward to graduating so I can do more research. My hours spent at the Broad thinking about my UROP are always the quickest hours of my week. I love the rabbit holes my research allows me to explore, and I hope that I find those over and over again as I apply and hopefully get into PhD programs. I look forward to exploring a new city after I graduate, too. I wouldn’t mind staying in Cambridge/Boston. I love it here. But I would welcome a chance to be somewhere new and embrace all the people and unique experiences it has to offer.

10 Breakthrough Technologies 2017: The Cell Atlas

Biology’s next mega-project will find out what we’re really made of.

Unraveling the Mysteries of Genomic Medicine: The Broad Institute's Jaw-Dropping Journey

Unraveling the Mysteries of Genomic Medicine: The Broad Institute's Jaw-Dropping JourneyWait till you hear this - the Broad Institute, headquartered in Kendall Square in Cambridge, Massachusetts, has been at the forefront of genomic medicine since its inception in 2004. Founded with an ambitious goal to fulfill the promise of genomic medicine, this renowned research institute has been making waves in the scientific community with its groundbreaking discoveries. Did you know that the Broad Institute was founded just three years after the Human Genome Project was completed, with the aim of leveraging the newly sequenced human genome to improve human health?A Brief History of the Broad InstituteThe Broad Institute has a rich history that dates back to 2003 when it was founded by Los Angeles-based philanthropists Eli and Edythe Broad. Initially, the institute was launched in 2004 with a generous donation from the Broad family, and since then, it has grown to become one of the world's leadi...

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Alex Shalek named director of the Institute for Medical Engineering and Science

Alex K. Shalek, the J. W. Kieckhefer Professor in the MIT Institute for Medical Engineering and Sciences (IMES) and Department of Chemistry, has been named the new director of IMES, effective Aug. 1.

“Professor Shalek’s substantial contributions to the scientific community as a researcher and educator have been exemplary. His extensive network across MIT, Harvard, and Mass General Brigham will be a tremendous asset as director of IMES,” says Anantha Chandrakasan, chief innovation and strategy officer, dean of the School of Engineering, and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “He will undoubtedly be an excellent leader, bringing his innovative approach and collaborative spirit to this new role.”

Shalek is a core member of IMES, a professor of chemistry, and holds several leadership positions, including director of the Health Innovation Hub. He is also an extramural member of MIT’s Koch Institute for Integrative Cancer Research; a member of the Ragon Institute of Mass General, MIT, and Harvard; an institute member of the Broad Institute of MIT and Harvard; an assistant in immunology at Mass General Brigham; and an instructor in health sciences and technology at Harvard Medical School.

The Shalek Lab’s research seeks to uncover how communities of cells work together within human tissues to support health, and how they become dysregulated in disease. By developing and applying innovative experimental and computational technologies, they are shedding light on a wide range of human health conditions.

Shalek and his team use a cross-disciplinary approach that combines genomics, chemical biology, and nanotechnology to develop platforms to profile and control cells and their interactions. Collaborating with researchers across the globe, they apply these tools to study human diseases in great detail. Their goal is to connect what occurs at a cellular level with what medical professionals observe in patients, paving the way for more precise ways to prevent and treat diseases. 

Over the course of his career, Shalek’s groundbreaking research has earned him widespread recognition and numerous awards and honors. These include an NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, an Alfred P. Sloan Research Fellowship in Chemistry, and an Avant-Garde (DP1 Pioneer) Award. Shalek has also been celebrated for his dedication as a faculty member, educator, and mentor. He was awarded the 2019-20 Harold E. Edgerton Faculty Achievement Award at MIT and the 2020 HMS Young Mentor Award.

Shalek received his bachelor’s degree in chemical physics from Columbia University and his master’s and PhD in chemical physics from Harvard University. Prior to joining MIT’s faculty in 2014, he was a postdoc at the Broad Institute.

Shalek succeeds Elazer Edelman, the Edward J. Poitras Professor in Medical Engineering and Science, who has led IMES since April 2018.

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CHARMed collaboration creates a potent therapy candidate for fatal prion diseases

Drug development is typically slow: The pipeline from basic research discoveries that provide the basis for a new drug to clinical trials and then production of a widely available medicine can take decades. But decades can feel impossibly far off to someone who currently has a fatal disease. Broad Institute of MIT and Harvard Senior Group Leader Sonia Vallabh is acutely aware of that race against time, because the topic of her research is a neurodegenerative and ultimately fatal disease — fatal familial insomnia, a type of prion disease — that she will almost certainly develop as she ages. 

Vallabh and her husband, Eric Minikel, switched careers and became researchers after they learned that Vallabh carries a disease-causing version of the prion protein gene and that there is no effective therapy for fatal prion diseases. The two now run a lab at the Broad Institute, where they are working to develop drugs that can prevent and treat these diseases, and their deadline for success is not based on grant cycles or academic expectations but on the ticking time bomb in Vallabh’s genetic code.

That is why Vallabh was excited to discover, when she entered into a collaboration with Whitehead Institute for Biomedical Research member Jonathan Weissman, that Weissman’s group likes to work at full throttle. In less than two years, Weissman, Vallabh, and their collaborators have developed a set of molecular tools called CHARMs that can turn off disease-causing genes such as the prion protein gene — as well as, potentially, genes coding for many other proteins implicated in neurodegenerative and other diseases — and they are refining those tools to be good candidates for use in human patients. Although the tools still have many hurdles to pass before the researchers will know if they work as therapeutics, the team is encouraged by the speed with which they have developed the technology thus far.

“The spirit of the collaboration since the beginning has been that there was no waiting on formality,” Vallabh says. “As soon as we realized our mutual excitement to do this, everything was off to the races.”

Co-corresponding authors Weissman and Vallabh and co-first authors Edwin Neumann, a graduate student in Weissman’s lab, and Tessa Bertozzi, a postdoc in Weissman’s lab, describe CHARM — which stands for Coupled Histone tail for Autoinhibition Release of Methyltransferase — in a paper published today in the journal Science.

“With the Whitehead and Broad Institutes right next door to each other, I don’t think there’s any better place than this for a group of motivated people to move quickly and flexibly in the pursuit of academic science and medical technology,” says Weissman, who is also a professor of biology at MIT and a Howard Hughes Medical Institute Investigator. “CHARMs are an elegant solution to the problem of silencing disease genes, and they have the potential to have an important position in the future of genetic medicines.”

To treat a genetic disease, target the gene

Prion disease, which leads to swift neurodegeneration and death, is caused by the presence of misshapen versions of the prion protein. These cause a cascade effect in the brain: the faulty prion proteins deform other proteins, and together these proteins not only stop functioning properly but also form toxic aggregates that kill neurons. The most famous type of prion disease, known colloquially as mad cow disease, is infectious, but other forms of prion disease can occur spontaneously or be caused by faulty prion protein genes.

Most conventional drugs work by targeting a protein. CHARMs, however, work further upstream, turning off the gene that codes for the faulty protein so that the protein never gets made in the first place. CHARMs do this by epigenetic editing, in which a chemical tag gets added to DNA in order to turn off or silence a target gene. Unlike gene editing, epigenetic editing does not modify the underlying DNA — the gene itself remains intact. However, like gene editing, epigenetic editing is stable, meaning that a gene switched off by CHARM should remain off. This would mean patients would only have to take CHARM once, as opposed to protein-targeting medications that must be taken regularly as the cells’ protein levels replenish.

Research in animals suggests that the prion protein isn’t necessary in a healthy adult, and that in cases of disease, removing the protein improves or even eliminates disease symptoms. In a person who hasn’t yet developed symptoms, removing the protein should prevent disease altogether. In other words, epigenetic editing could be an effective approach for treating genetic diseases such as inherited prion diseases. The challenge is creating a new type of therapy.

Fortunately, the team had a good template for CHARM: a research tool called CRISPRoff that Weissman’s group previously developed for silencing genes. CRISPRoff uses building blocks from CRISPR gene editing technology, including the guide protein Cas9 that directs the tool to the target gene. CRISPRoff silences the targeted gene by adding methyl groups, chemical tags that prevent the gene from being transcribed, or read into RNA, and so from being expressed as protein. When the researchers tested CRISPRoff’s ability to silence the prion protein gene, they found that it was effective and stable.

Several of its properties, though, prevented CRISPRoff from being a good candidate for a therapy. The researchers’ goal was to create a tool based on CRISPRoff that was just as potent but also safe for use in humans, small enough to deliver to the brain, and designed to minimize the risk of silencing the wrong genes or causing side effects.

From research tool to drug candidate

Led by Neumann and Bertozzi, the researchers began engineering and applying their new epigenome editor. The first problem that they had to tackle was size, because the editor needs to be small enough to be packaged and delivered to specific cells in the body. Delivering genes into the human brain is challenging; many clinical trials have used adeno-associated viruses (AAVs) as gene-delivery vehicles, but these are small and can only contain a small amount of genetic code. CRISPRoff is way too big; the code for Cas9 alone takes up most of the available space.

The Weissman lab researchers decided to replace Cas9 with a much smaller zinc finger protein (ZFP). Like Cas9, ZFPs can serve as guide proteins to direct the tool to a target site in DNA. ZFPs are also common in human cells, meaning they are less likely to trigger an immune response against themselves than the bacterial Cas9.

Next, the researchers had to design the part of the tool that would silence the prion protein gene. At first, they used part of a methyltransferase, a molecule that adds methyl groups to DNA, called DNMT3A. However, in the particular configuration needed for the tool, the molecule was toxic to the cell. The researchers focused on a different solution: Instead of delivering outside DNMT3A as part of the therapy, the tool is able to recruit the cell’s own DNMT3A to the prion protein gene. This freed up precious space inside of the AAV vector and prevented toxicity.

The researchers also needed to activate DNMT3A. In the cell, DNMT3A is usually inactive until it interacts with certain partner molecules. This default inactivity prevents accidental methylation of genes that need to remain turned on. Neumann came up with an ingenious way around this by combining sections of DNMT3A’s partner molecules and connecting these to ZFPs that bring them to the prion protein gene. When the cell’s DNMT3A comes across this combination of parts, it activates, silencing the gene.

“From the perspectives of both toxicity and size, it made sense to recruit the machinery that the cell already has; it was a much simpler, more elegant solution,” Neumann says. “Cells are already using methyltransferases all of the time, and we’re essentially just tricking them into turning off a gene that they would normally leave turned on.”

Testing in mice showed that ZFP-guided CHARMs could eliminate more than 80 percent of the prion protein in the brain, while previous research has shown that as little as 21 percent elimination can improve symptoms.

Once the researchers knew that they had a potent gene silencer, they turned to the problem of off-target effects. The genetic code for a CHARM that gets delivered to a cell will keep producing copies of the CHARM indefinitely. However, after the prion protein gene is switched off, there is no benefit to this, only more time for side effects to develop, so they tweaked the tool so that after it turns off the prion protein gene, it then turns itself off.

Meanwhile, a complementary project from Broad Institute scientist and collaborator Benjamin Deverman’s lab, focused on brain-wide gene delivery and published in Science on May 17, has brought the CHARM technology one step closer to being ready for clinical trials. Although naturally occurring types of AAV have been used for gene therapy in humans before, they do not enter the adult brain efficiently, making it impossible to treat a whole-brain disease like prion disease. Tackling the delivery problem, Deverman’s group has designed an AAV vector that can get into the brain more efficiently by leveraging a pathway that naturally shuttles iron into the brain. Engineered vectors like this one make a therapy like CHARM one step closer to reality.

Thanks to these creative solutions, the researchers now have a highly effective epigenetic editor that is small enough to deliver to the brain, and that appears in cell culture and animal testing to have low toxicity and limited off-target effects.

“It’s been a privilege to be part of this; it’s pretty rare to go from basic research to therapeutic application in such a short amount of time,” Bertozzi says. “I think the key was forming a collaboration that took advantage of the Weissman lab’s tool-building experience, the Vallabh and Minikel lab’s deep knowledge of the disease, and the Deverman lab’s expertise in gene delivery.”

Looking ahead

With the major elements of the CHARM technology solved, the team is now fine-tuning their tool to make it more effective, safer, and easier to produce at scale, as will be necessary for clinical trials. They have already made the tool modular, so that its various pieces can be swapped out and future CHARMs won’t have to be programmed from scratch. CHARMs are also currently being tested as therapeutics in mice. 

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Envisioning a time when people age without fear of dementia

The mathematician and computer scientist Richard Hamming once gave a talk about doing great research. “He who works with the door open gets all kinds of interruptions, but he also occasionally gets clues as to what the world is and what might be important,” Hamming said, emphasizing the importance of open-mindedness and scientific development.

William Li came across this quote as a high school student seeking to dedicate himself to research but unsure how to begin. “I think that science is kind of an opaque area to break into. It’s hard to know what you’re supposed to be doing from time to time,” Li explains.

A double-major in physics and computer science, Li has taken this advice to heart. Keeping his “office door” open has led him to a variety of research projects, from neuroimaging to genomics, that shaped his long-term goal: to become a physician-scientist who moves the needle on Alzheimer’s disease.

Li’s interest in working with patients in a clinical setting was spurred by his grandfather, who was a doctor. In high school, he began volunteering in retirement homes and at the Byrd Alzheimer’s Center and Research Institute at the University of South Florida. Through this work, Li witnessed the devastating effects Alzheimer’s disease has on both those diagnosed and their loved ones.

But that isn’t the only thing about Alzheimer’s that has grabbed his interest. With no cure available, and relatively little known about its cause, the disease is also a compelling scientific problem. “Beyond its human impact, Alzheimer’s represents a frontier of our understanding of human disease,” Li says.

Starting in the fall, Li will begin an MD/PhD program “for the better part of the coming decade.” Following that, he hopes to secure a residency in radiology or neurology, and then to teach and do research while simultaneously practicing medicine. His ultimate goal is a big one — to help develop a cure for Alzheimer’s.

Pursing knowledge

Research has been the highlight of Li’s career at MIT. He says, “To me personally, research means being able to contribute to a body of knowledge built upon by generations of minds in the past. I see modern science and technology as a pinnacle of human achievement, and it’s a dream come true to be able to add to this work.”

In a normal week during the academic semester, Li can spend up to 15 hours in the lab. His research projects have addressed very different topics, but both have guided him toward his current goals.

In the Soljačić and Johnson groups in the Research Laboratory of Electronics, Li he has worked in nanophotonics, a field concerned with controlling light by designing structures the size of a wavelength, for optical and X-ray images, among other applications. 

Li has worked on making X-ray imaging safer and more effective for medical screenings. He also focuses on using computational methods to design nanophotonic device elements for higher-resolution imaging. “Imaging technologies in the future will have pretty enormous applications both for understanding disease and for being able to catch diseases early through diagnosis,” he says.

In his sophomore year, Li began working at the lab of Professor Manolis Kellis at the Broad Institute of MIT and Harvard, using computational tools to study genetic variation among Alzheimer’s patients and how this relates to the disease itself. In this way, the disease can be broken down into subtypes, explains Li, which will make it easier to understand and treat. Last summer, Li won a SuperUROP Outstanding Research Award for this project.

Forging connections

When Li first joined the Kellis lab, the field of genomics seemed vast and overwhelming. To combat this, he started an academic journal club. In the club, Li and his peers would read research papers together and discuss them. In the fashion of a traditional journal club, one person would present at each meeting. Club participants encouraged each other to focus on any research they found exciting, ranging over the past century. As the club has continued, members have started to present their own research to the group as well. “It’s fun seeing what my friends are interested in,” Li says.

Li also served as the collegiate relations co-chair of MIT’s Pre-Medical Society. Here he was responsible for organizing an annual meeting between all pre-med students of the greater Boston area. This mixer was held for pre-med students to other local students and learn from pre-medical advisors and alumni of various Boston schools.

Among the several communities Li is a part of at MIT, his dormitory holds a special place in his heart. Next House, MIT’s largest dorm building, is the place Li has called home since his junior year. Since moving in, he has immersed himself in the living community by assuming roles in several activities hosted by the dorm, such as Thanksgiving dinner.

“I’m very happy to be part of the Next House community. It’s a pretty fantastic place, and I would say that my quality of social life has increased a lot since moving here,” he states.

Along with large events, Li also appreciates the weekly traditions he has created with his Next House friends. Each Sunday, for example, Li joins members of his dorm wing for a 15-minute workout. He says he enjoys exercising in the group setting and frequently attends the gym with his friends, too.