Category: Profiles

Staff Spotlight: Lighting up biology’s basement lab

Senior Technical Instructor Vanessa Cheung ’02 brings the energy, experience, and excitement needed to educate students in the biology teaching lab.

Samantha Edelen | Department of Biology
April 29, 2025

For more than 30 years, Course 7 (Biology) students have descended to the expansive, windowless basement of Building 68 to learn practical skills that are the centerpiece of undergraduate biology education at the Institute. The lines of benches and cabinets of supplies that make up the underground MIT Biology Teaching Lab could easily feel dark and isolated.

In the corner of this room, however, sits Senior Technical Instructor Vanessa Cheung ’02, who manages to make the space seem sunny and communal.

“We joke that we could rig up a system of mirrors to get just enough daylight to bounce down from the stairwell,” Cheung says with a laugh. “It is a basement, but I am very lucky to have this teaching lab space. It is huge and has everything we need.”

This optimism and gratitude fostered by Cheung is critical, as MIT undergrad students enrolled in classes 7.002 (Fundamentals of Experimental Molecular Biology) and 7.003 (Applied Molecular Biology Laboratory) spend four-hour blocks in the lab each week, learning the foundations of laboratory technique and theory for biological research from Cheung and her colleagues.

Running toward science education

Cheung’s love for biology can be traced back to her high school cross country and track coach, who also served as her second-year biology teacher. The sport and the fundamental biological processes she was learning about in the classroom were, in fact, closely intertwined.

“He told us about how things like ATP [adenosine triphosphate] and the energy cycle would affect our running,” she says. “Being able to see that connection really helped my interest in the subject.”

That inspiration carried her through a move from her hometown of Pittsburgh, Pennsylvania, to Cambridge, Massachusetts, to pursue an undergraduate degree at MIT, and through her thesis work to earn a PhD in genetics at Harvard Medical School. She didn’t leave running behind either: To this day, she can often be found on the Charles River Esplanade, training for her next marathon.

She discovered her love of teaching during her PhD program. She enjoyed guiding students so much that she spent an extra semester as a teaching assistant, outside of the one required for her program.

“I love research, but I also really love telling people about research,” Cheung says.

Cheung herself describes lab instruction as the “best of both worlds,” enabling her to pursue her love of teaching while spending every day at the bench, doing experiments. She emphasizes for students the importance of being able not just to do the hands-on technical lab work, but also to understand the theory behind it.

“The students can tend to get hung up on the physical doing of things — they are really concerned when their experiments don’t work,” she says. “We focus on teaching students how to think about being in a lab — how to design an experiment and how to analyze the data.”

Although her talent for teaching and passion for science led her to the role, Cheung doesn’t hesitate to identify the students as her favorite part of the job.

“It sounds cheesy, but they really do keep the job very exciting,” she says.

Using mind and hand in the lab

Cheung is the type of person who lights up when describing how much she “loves working with yeast.”

“I always tell the students that maybe no one cares about yeast except me and like three other people in the world, but it is a model organism that we can use to apply what we learn to humans,” Cheung explains.

Though mastering basic lab skills can make hands-on laboratory courses feel “a bit cookbook,” Cheung is able to get the students excited with her enthusiasm and clever curriculum design.

“The students like things where they can get their own unique results, and things where they have a little bit of freedom to design their own experiments,” she says. So, the lab curriculum incorporates opportunities for students to do things like identify their own unique yeast mutants and design their own questions to test in a chemical engineering module.

Part of what makes theory as critical as technique is that new tools and discoveries are made frequently in biology, especially at MIT. For example, there has been a shift from a focus on RNAi to CRISPR as a popular lab technique in recent years, and Cheung muses that CRISPR itself may be overshadowed within only a few more years — keeping students learning at the cutting edge of biology is always on Cheung’s mind.

“Vanessa is the heart, soul, and mind of the biology lab courses here at MIT, embodying ‘mens et manus’ [‘mind and hand’],” says technical lab instructor and Biology Teaching Lab Manager Anthony Fuccione.

Support for all students

Cheung’s ability to mentor and guide students earned her a School of Science Dean’s Education and Advising Award in 2012, but her focus isn’t solely on MIT undergraduate students.

In fact, according to Cheung, the earlier students can be exposed to science, the better. In addition to her regular duties, Cheung also designs curriculum and teaches in the LEAH Knox Scholars Program. The two-year program provides lab experience and mentorship for low-income Boston- and Cambridge-area high school students.

Paloma Sanchez-Jauregui, outreach programs coordinator who works with Cheung on the program, says Cheung has a standout “growth mindset” that students really appreciate.

“Vanessa teaches students that challenges — like unexpected PCR results — are part of the learning process,” Sanchez-Jauregui says. “Students feel comfortable approaching her for help troubleshooting experiments or exploring new topics.”

Cheung’s colleagues report that they admire not only her talents, but also her focus on supporting those around her. Technical Instructor and colleague Eric Chu says Cheung “offers a lot of help to me and others, including those outside of the department, but does not expect reciprocity.”

Professor of biology and co-director of the Department of Biology undergraduate program Adam Martin says he “rarely has to worry about what is going on in the teaching lab.” According to Martin, Cheung is ”flexible, hard-working, dedicated, and resilient, all while being kind and supportive to our students. She is a joy to work with.”

Staff Spotlight: Always looking to home

Mingmar Sherpa, a researcher in the Martin Lab in the Department of Biology, has remained connected to his home in Nepal at every step of his career.

Ekaterina Khalizeva | Department of Biology
April 29, 2025

For Mingmar Sherpa, a senior research support associate in the Martin Lab in the Department of Biology, community is more than just his colleagues in the lab, where he studies how mechanical forces affect cell division timing during embryogenesis. On his long and winding path to MIT, he never left behind the people he grew up among in Nepal. Sherpa has been dedicated, every step of his career — from rural Solukhumbu to Kathmandu to Alabama to Cambridge — to advancing education and health care among his people in any way he can.

Despite working more than 7,000 miles away from home, Mingmar Sherpa makes every effort to keep himself connected to his community in Nepal. Every month, for example, he sends home money to support a computer lab that he established in his hometown in rural Solukhumbu, the district of Nepal that houses Mount Everest — just $250 a month covers the costs of a teacher’s salary, electricity, internet, and a space to teach. In this lab, almost 250 students thus far have learned computer skills essential to working in today’s digitally driven world. In college, Sherpa also started The Bright Vision Foundation (The Bright Future), an organization to support health and education in Nepal, and during the pandemic raised funds to provide personal protective equipment (PPE) and health care services across his home country.

While Sherpa’s ambition to help his home can be traced back to his childhood, he didn’t have it all figured out from the start, and found inspiration at each step of his career.

“This mindset of giving back to the community, helping policymakers or establishing an organization to help people do science, helping the scientific community to find cures for diseases — all these ideas came to me along the way,” Sherpa says. “It is the journey that matters.”

A journey driven by hope and optimism

“Sherpa” is a reference to the ethnic group native to the mountainous regions of Nepal and Tibet, whose members are well-known for their mountaineering skills, which they use to guide and assist tourists who want to climb Mount Everest. Growing up in rural Solukhumbu, Sherpa was surrounded by people working in the tourism industry; few other occupations appeared feasible. There was just one hospital for the whole district, requiring locals to walk for days to get medical assistance.

The youngest of seven siblings, Sherpa went to an English-language middle school, which he had to walk for over an hour to get to. He excelled there, soon becoming the top student in his class and passing the national exam with distinction — success that allowed him to both dream of and accomplish a move to Kathmandu, the capital city of Nepal, to study in the best school in the country.

It was an overwhelming transition, surrounded as he was for the first time by people from a very different social class, privileged with far more technological resources. The gaps between this well-equipped community and the one he left back home became increasingly obvious and left a strong impression on Sherpa.

There, he started thinking about how to use his newly acquired access to education and technology to uplift his community at home. He was especially fascinated by questions surrounding biology and human health, and next set his sights on attending college in the United States.

“If I came to the U.S., I could learn skills which I could not learn in Nepal,” he says. “I could prepare myself to solve the problems that I want to solve.”

At the University of Alabama in Birmingham, Sherpa continued to deepen his passion for biological science and joined a research lab. Through that work, he discovered the joys of basic research and the diverse set of skills it fosters.

“I joined the lab to learn science, but to do science, you need other skills, like research communication,” he says. “I was learning unintentionally from being in a research position.”

When Covid-19 spread around the globe, Sherpa wanted to apply the expertise and resources he had gained to help his people address the crisis. It was then that he started The Bright Vision Foundation, an organization aiming to raise the standards of health care and education in underserved communities in Nepal. Through the foundation, he raised funds to distribute PPE, provide health care services, and set up the computer lab in his childhood home.

“Today’s world is all about technology and innovation, but here are good people in my community who don’t even know about computers,” he says.

With the help of his brother, who serves as the lab instructor, and his parents, who provide the space and support the lab, and Sherpa’s own fundraising, he aims to help youths from backgrounds similar to his own be better prepared for the technologically advanced, globalized world of today.

The MIT chapter

Now, at MIT, Sherpa speaks with deep appreciation of the opportunities that the university has opened up for him — the people he has been meeting here, and the skills he has been learning.

Professor of biology Adam C. Martin, Sherpa’s principal investigator, views making sure that international trainees like Mingmar are aware of the wide range of opportunities MIT offers — whether it be workshops, collaborations, networking and funding possibilities, or help with the pathway toward graduate school — as a key part of creating a supportive environment.

Understanding the additional burdens on international trainees gives Martin extra appreciation for Sherpa’s perseverance, motivation, and desire to share his culture with the lab, sharing Nepalese food and providing context for Nepalese customs.

Being at such a research-intensive institution as MIT has helped Sherpa further clarify his goals and his view of the paths he can take to achieve them. Since college, his three passions have been intertwined: leadership, research, and human health.

Sherpa will pursue a PhD in biomedical and biological sciences with a focus in cancer biology at Cornell University in the fall. In the longer term, he plans to focus on developing policy to improve public health.

Although Sherpa recognizes that Nepal is not the only place that might need his help, he has a sharp focus and an acute sense of what he is best positioned to do now. Sherpa is gearing up to organize a health camp in the spring to bring doctors to rural areas in Nepal, not only to provide care, but also to gather data on nutrition and health in different regions of the country.

“I cannot, in a day, or even a year, bring the living conditions of people in vulnerable communities up to a higher level, but I can slowly increase the living standard of people in less-developed communities, especially in Nepal,” he says. “There might be other parts of the world which are even more vulnerable than Nepal, but I haven’t explored them yet. But I know my community in Nepal, so I want to help improve people’s lives there.”

At the core of problem-solving

Stuart Levine ’97, director of MIT’s BioMicro Center, keeps departmental researchers at the forefront of systems biology.

Samantha Edelen | Department of Biology
March 19, 2025

As director of the MIT BioMicro Center (BMC), Stuart Levine ’97 wholeheartedly embraces the variety of challenges he tackles each day. One of over 50 core facilities providing shared resources across the Institute, the BMC supplies integrated high-throughput genomics, single-cell and spatial transcriptomic analysis, bioinformatics support, and data management to researchers across MIT.

“Every day is a different day,” Levine says, “there are always new problems, new challenges, and the technology is continuing to move at an incredible pace.” After more than 15 years in the role, Levine is grateful that the breadth of his work allows him to seek solutions for so many scientific problems.

By combining bioinformatics expertise with biotech relationships and a focus on maximizing the impact of the center’s work, Levine brings the broad range of skills required to match the diversity of questions asked by researchers in MIT’s Department of Biology.

Expansive expertise

Biology first appealed to Levine as an MIT undergraduate taking class 7.012 (Introduction to Biology), thanks to the charisma of instructors Professor Eric Lander and Amgen Professor Emerita Nancy Hopkins. After earning his PhD in biochemistry from Harvard University and Massachusetts General Hospital, Levine returned to MIT for postdoctoral work with Professor Richard Young, core member at the Whitehead Institute for Biomedical Research.

In the Young Lab, Levine found his calling as an informaticist and ultimately decided to stay at MIT. Here, his work has a wide-ranging impact: the BMC serves over 100 labs annually, from the the Computer Science and Artificial Intelligence Laboratory and the departments of Brain and Cognitive Sciences; Earth, Atmospheric and Planetary Sciences; Chemical Engineering; Mechanical Engineering; and, of course, Biology.

“It’s a fun way to think about science,” Levine says, noting that he applies his knowledge and streamlines workflows across these many disciplines by “truly and deeply understanding the instrumentation complexities.”

This depth of understanding and experience allows Levine to lead what longtime colleague Professor Laurie Boyer describes as “a state-of-the-art core that has served so many faculty and provides key training opportunities for all.” He and his team work with cutting-edge, finely tuned scientific instruments that generate vast amounts of bioinformatics data, then use powerful computational tools to store, organize, and visualize the data collected, contributing to research on topics ranging from host-parasite interactions to proposed tools for NASA’s planetary protection policy.

Staying ahead of the curve

With a scientist directing the core, the BMC aims to enable researchers to “take the best advantage of systems biology methods,” says Levine. These methods use advanced research technologies to do things like prepare large sets of DNA and RNA for sequencing, read DNA and RNA sequences from single cells, and localize gene expression to specific tissues.

Levine presents a lightweight, clear rectangle about the width of a cell phone and the length of a VHS cassette.

“This is a flow cell that can do 20 human genomes to clinical significance in two days — 8 billion reads,” he says. “There are newer instruments with several times that capacity available as well.”

The vast majority of research labs do not need that kind of power, but the Institute, and its researchers as a whole, certainly do. Levine emphasizes that “the ROI [return on investment] for supporting shared resources is extremely high because whatever support we receive impacts not just one lab, but all of the labs we support. Keeping MIT’s shared resources at the bleeding edge of science is critical to our ability to make a difference in the world.”

To stay at the edge of research technology, Levine maintains company relationships, while his scientific understanding allows him to educate researchers on what is possible in the space of modern systems biology. Altogether, these attributes enable Levine to help his researcher clients “push the limits of what is achievable.”

The man behind the machines

Each core facility operates like a small business, offering specialized services to a diverse client base across academic and industry research, according to Amy Keating, Jay A. Stein (1968) Professor of Biology and head of the Department of Biology. She explains that “the PhD-level education and scientific and technological expertise of MIT’s core directors are critical to the success of life science research at MIT and beyond.”

While Levine clearly has the education and expertise, the success of the BMC “business” is also in part due to his tenacity and focus on results for the core’s users.

He was recognized by the Institute with the MIT Infinite Mile Award in 2015 and the MIT Excellence Award in 2017, for which one nominator wrote, “What makes Stuart’s leadership of the BMC truly invaluable to the MIT community is his unwavering dedication to producing high-quality data and his steadfast persistence in tackling any type of troubleshooting needed for a project. These attributes, fostered by Stuart, permeate the entire culture of the BMC.”

“He puts researchers and their research first, whether providing education, technical services, general tech support, or networking to collaborators outside of MIT,” says Noelani Kamelamela, lab manager of the BMC. “It’s all in service to users and their projects.”

Tucked into the far back corner of the BMC lab space, Levine’s office is a fitting symbol of his humility. While his guidance and knowledge sit at the center of what elevates the BMC beyond technical support, he himself sits away from the spotlight, resolutely supporting others to advance science.

“Stuart has always been the person, often behind the scenes, that pushes great science, ideas, and people forward,” Boyer says. “His knowledge and advice have truly allowed us to be at the leading edge in our work.”

Helping the immune system attack tumors

Stefani Spranger is working to discover why some cancers don’t respond to immunotherapy, in hopes of making them more vulnerable to it.

Anne Trafton | MIT News
February 26, 2025

In addition to patrolling the body for foreign invaders, the immune system also hunts down and destroys cells that have become cancerous or precancerous. However, some cancer cells end up evading this surveillance and growing into tumors.

Once established, tumor cells often send out immunosuppressive signals, which leads T cells to become “exhausted” and unable to attack the tumor. In recent years, some cancer immunotherapy drugs have shown great success in rejuvenating those T cells so they can begin attacking tumors again.

While this approach has proven effective against cancers such as melanoma, it doesn’t work as well for others, including lung and ovarian cancer. MIT Associate Professor Stefani Spranger is trying to figure out how those tumors are able to suppress immune responses, in hopes of finding new ways to galvanize T cells into attacking them.

“We really want to understand why our immune system fails to recognize cancer,” Spranger says. “And I’m most excited about the really hard-to-treat cancers because I think that’s where we can make the biggest leaps.”

Her work has led to a better understanding of the factors that control T-cell responses to tumors, and raised the possibility of improving those responses through vaccination or treatment with immune-stimulating molecules called cytokines.

“We’re working on understanding what exactly the problem is, and then collaborating with engineers to find a good solution,” she says.

Jumpstarting T cells

As a student in Germany, where students often have to choose their college major while still in high school, Spranger envisioned going into the pharmaceutical industry and chose to major in biology. At Ludwig Maximilian University in Munich, her course of study began with classical biology subjects such as botany and zoology, and she began to doubt her choice. But, once she began taking courses in cell biology and immunology, her interest was revived and she continued into a biology graduate program at the university.

During a paper discussion class early in her graduate school program, Spranger was assigned to a Science paper on a promising new immunotherapy treatment for melanoma. This strategy involves isolating tumor-infiltrating T-cells during surgery, growing them into large numbers, and then returning them to the patient. For more than 50 percent of those patients, the tumors were completely eliminated.

“To me, that changed the world,” Spranger recalls. “You can take the patient’s own immune system, not really do all that much to it, and then the cancer goes away.”

Spranger completed her PhD studies in a lab that worked on further developing that approach, known as adoptive T-cell transfer therapy. At that point, she still was leaning toward going into pharma, but after finishing her PhD in 2011, her husband, also a biologist, convinced her that they should both apply for postdoc positions in the United States.

They ended up at the University of Chicago, where Spranger worked in a lab that studies how the immune system responds to tumors. There, she discovered that while melanoma is usually very responsive to immunotherapy, there is a small fraction of melanoma patients whose T cells don’t respond to the therapy at all. That got her interested in trying to figure out why the immune system doesn’t always respond to cancer the way that it should, and in finding ways to jumpstart it.

During her postdoc, Spranger also discovered that she enjoyed mentoring students, which she hadn’t done as a graduate student in Germany. That experience drew her away from going into the pharmaceutical industry, in favor of a career in academia.

“I had my first mentoring teaching experience having an undergrad in the lab, and seeing that person grow as a scientist, from barely asking questions to running full experiments and coming up with hypotheses, changed how I approached science and my view of what academia should be for,” she says.

Modeling the immune system

When applying for faculty jobs, Spranger was drawn to MIT by the collaborative environment of MIT and its Koch Institute for Integrative Cancer Research, which offered the chance to collaborate with a large community of engineers who work in the field of immunology.

“That community is so vibrant, and it’s amazing to be a part of it,” she says.

Building on the research she had done as a postdoc, Spranger wanted to explore why some tumors respond well to immunotherapy, while others do not. For many of her early studies, she used a mouse model of non-small-cell lung cancer. In human patients, the majority of these tumors do not respond well to immunotherapy.

“We build model systems that resemble each of the different subsets of non-responsive non-small cell lung cancer, and we’re trying to really drill down to the mechanism of why the immune system is not appropriately responding,” she says.

As part of that work, she has investigated why the immune system behaves differently in different types of tissue. While immunotherapy drugs called checkpoint inhibitors can stimulate a strong T-cell response in the skin, they don’t do nearly as much in the lung. However, Spranger has shown that T cell responses in the lung can be improved when immune molecules called cytokines are also given along with the checkpoint inhibitor.

Those cytokines work, in part, by activating dendritic cells — a class of immune cells that help to initiate immune responses, including activation of T cells.

“Dendritic cells are the conductor for the orchestra of all the T cells, although they’re a very sparse cell population,” Spranger says. “They can communicate which type of danger they sense from stressed cells and then instruct the T cells on what they have to do and where they have to go.”

Spranger’s lab is now beginning to study other types of tumors that don’t respond at all to immunotherapy, including ovarian cancer and glioblastoma. Both the brain and the peritoneal cavity appear to suppress T-cell responses to tumors, and Spranger hopes to figure out how to overcome that immunosuppression.

“We’re specifically focusing on ovarian cancer and glioblastoma, because nothing’s working right now for those cancers,” she says. “We want to understand what we have to do in those sites to induce a really good anti-tumor immune response.”

Professor Anthony Sinskey, biologist, inventor, entrepreneur, and Center for Biomedical Innovation co-founder, dies at 84

Colleagues remember the longtime MIT professor as a supportive, energetic collaborator who seemed to know everyone at the Institute.

Zach Winn | MIT News
February 20, 2025

Longtime MIT Professor Anthony “Tony” Sinskey ScD ’67, who was also the co-founder and faculty director of the Center for Biomedical Innovation (CBI), passed away on Feb. 12 at his home in New Hampshire. He was 84.

Deeply engaged with MIT, Sinskey left his mark on the Institute as much through the relationships he built as the research he conducted. Colleagues say that throughout his decades on the faculty, Sinskey’s door was always open.

“He was incredibly generous in so many ways,” says Graham Walker, an American Cancer Society Professor at MIT. “He was so willing to support people, and he did it out of sheer love and commitment. If you could just watch Tony in action, there was so much that was charming about the way he lived. I’ve said for years that after they made Tony, they broke the mold. He was truly one of a kind.”

Sinskey’s lab at MIT explored methods for metabolic engineering and the production of biomolecules. Over the course of his research career, he published more than 350 papers in leading peer-reviewed journals for biology, metabolic engineering, and biopolymer engineering, and filed more than 50 patents. Well-known in the biopharmaceutical industry, Sinskey contributed to the founding of multiple companies, including Metabolix, Tepha, Merrimack Pharmaceuticals, and Genzyme Corporation. Sinskey’s work with CBI also led to impactful research papers, manufacturing initiatives, and educational content since its founding in 2005.

Across all of his work, Sinskey built a reputation as a supportive, collaborative, and highly entertaining friend who seemed to have a story for everything.

“Tony would always ask for my opinions — what did I think?” says Barbara Imperiali, MIT’s Class of 1922 Professor of Biology and Chemistry, who first met Sinskey as a graduate student. “Even though I was younger, he viewed me as an equal. It was exciting to be able to share my academic journey with him. Even later, he was continually opening doors for me, mentoring, connecting. He felt it was his job to get people into a room together to make new connections.”

Sinskey grew up in the small town of Collinsville, Illinois, and spent nights after school working on a farm. For his undergraduate degree, he attended the University of Illinois, where he got a job washing dishes at the dining hall. One day, as he recalled in a 2020 conversation, he complained to his advisor about the dishwashing job, so the advisor offered him a job washing equipment in his microbiology lab.

In a development that would repeat itself throughout Sinskey’s career, he befriended the researchers in the lab and started learning about their work. Soon he was showing up on weekends and helping out. The experience inspired Sinskey to go to graduate school, and he only applied to one place.

Sinskey earned his ScD from MIT in nutrition and food science in 1967. He joined MIT’s faculty a few years later and never left.

“He loved MIT and its excellence in research and education, which were incredibly important to him,” Walker says. “I don’t know of another institution this interdisciplinary — there’s barely a speed bump between departments — so you can collaborate with anybody. He loved that. He also loved the spirit of entrepreneurship, which he thrived on. If you heard somebody wanted to get a project done, you could run around, get 10 people, and put it together. He just loved doing stuff like that.”

Working across departments would become a signature of Sinskey’s research. His original office was on the first floor of MIT’s Building 56, right next to the parking lot, so he’d leave his door open in the mornings and afternoons and colleagues would stop in and chat.

“One of my favorite things to do was to drop in on Tony when I saw that his office door was open,” says Chris Kaiser, MIT’s Amgen Professor of Biology. “We had a whole range of things we liked to catch up on, but they always included his perspectives looking back on his long history at MIT. It also always included hopes for the future, including tracking trajectories of MIT students, whom he doted on.”

Long before the internet, colleagues describe Sinskey as a kind of internet unto himself, constantly leveraging his vast web of relationships to make connections and stay on top of the latest science news.

“He was an incredibly gracious person — and he knew everyone,” Imperiali says. “It was as if his Rolodex had no end. You would sit there and he would say, ‘Call this person.’ or ‘Call that person.’ And ‘Did you read this new article?’ He had a wonderful view of science and collaboration, and he always made that a cornerstone of what he did. Whenever I’d see his door open, I’d grab a cup of tea and just sit there and talk to him.”

When the first recombinant DNA molecules were produced in the 1970s, it became a hot area of research. Sinskey wanted to learn more about recombinant DNA, so he hosted a large symposium on the topic at MIT that brought in experts from around the world.

“He got his name associated with recombinant DNA for years because of that,” Walker recalls. “People started seeing him as Mr. Recombinant DNA. That kind of thing happened all the time with Tony.”

Sinskey’s research contributions extended beyond recombinant DNA into other microbial techniques to produce amino acids and biodegradable plastics. He co-founded CBI in 2005 to improve global health through the development and dispersion of biomedical innovations. The center adopted Sinskey’s collaborative approach in order to accelerate innovation in biotechnology and biomedical research, bringing together experts from across MIT’s schools.

“Tony was at the forefront of advancing cell culture engineering principles so that making biomedicines could become a reality. He knew early on that biomanufacturing was an important step on the critical path from discovering a drug to delivering it to a patient,” says Stacy Springs, the executive director of CBI. “Tony was not only my boss and mentor, but one of my closest friends. He was always working to help everyone reach their potential, whether that was a colleague, a former or current researcher, or a student. He had a gentle way of encouraging you to do your best.”

“MIT is one of the greatest places to be because you can do anything you want here as long as it’s not a crime,” Sinskey joked in 2020. “You can do science, you can teach, you can interact with people — and the faculty at MIT are spectacular to interact with.”

Sinskey shared his affection for MIT with his family. His wife, the late ChoKyun Rha ’62, SM ’64, SM ’66, ScD ’67, was a professor at MIT for more than four decades and the first woman of Asian descent to receive tenure at MIT. His two sons also attended MIT — Tong-ik Lee Sinskey ’79, SM ’80 and Taeminn Song MBA ’95, who is the director of strategy and strategic initiatives for MIT Information Systems and Technology (IS&T).

Song recalls: “He was driven by same goal my mother had: to advance knowledge in science and technology by exploring new ideas and pushing everyone around them to be better.”

Around 10 years ago, Sinskey began teaching a class with Walker, Course 7.21/7.62 (Microbial Physiology). Walker says their approach was to treat the students as equals and learn as much from them as they taught. The lessons extended beyond the inner workings of microbes to what it takes to be a good scientist and how to be creative. Sinskey and Rha even started inviting the class over to their home for Thanksgiving dinner each year.

“At some point, we realized the class was turning into a close community,” Walker says. “Tony had this endless supply of stories. It didn’t seem like there was a topic in biology that Tony didn’t have a story about either starting a company or working with somebody who started a company.”

Over the last few years, Walker wasn’t sure they were going to continue teaching the class, but Sinskey remarked it was one of the things that gave his life meaning after his wife’s passing in 2021. That decided it.

After finishing up this past semester with a class-wide lunch at Legal Sea Foods, Sinskey and Walker agreed it was one of the best semesters they’d ever taught.

In addition to his two sons, Sinskey is survived by his daughter-in-law Hyunmee Elaine Song, five grandchildren, and two great grandsons. He has two brothers, Terry Sinskey (deceased in 1975) and Timothy Sinskey, and a sister, Christine Sinskey Braudis.

Gifts in Sinskey’s memory can be made to the ChoKyun Rha (1962) and Anthony J Sinskey (1967) Fund.

Alumni Profile: Desmond Edwards, SB ’22

An interest in translating medicine for a wider audience

School of Science
February 6, 2025

Growing up hearing both English and Patois in rural Jamaica, he always had an interest in understanding other languages, so he studied French in high school and minored in it at MIT. As a child with persistent illnesses, he was frustrated that doctors couldn’t explain the “how” and “why” of what was happening in his body. “I wanted to understand how an entity so small that we can’t even see it with most microscopes is able to get into a massively intricate human body and completely shut it down in a matter of days,” he says.

Edwards, now an MIT graduate and a PhD candidate in microbiology and immunology at Stanford University—with a deferred MD admission in hand as well—feels closer to understanding things. The financial support he received at MIT from the Class of 1975 Scholarship Fund, he says, was one major reason that he chose MIT.

Support for research and discovery

I took a three-week Independent Activities Period boot camp designed to expose first-years with little or no research background to basic molecular biology and microbiology techniques. We had guidance from the professor and teaching assistants, but it was up to us what path we took. That intellectual freedom was part of what made me fall in love with academic research. The lecturer, Mandana Sassanfar, made it her personal mission to connect interested students to Undergraduate Research Opportunities Program placements, which is how I found myself in Professor Rebecca Lamason’s lab.

At the end of my first year, I debated whether to prioritize my academic research projects or leave for a higher-paying summer internship. My lab helped me apply for the Peter J. Eloranta Summer Undergraduate Research Fellowship, which provided funding that allowed me to stay for the summer, and I ended up staying in the lab for the rest of my time at MIT. One paper I coauthored (about developing new genetic tools to control pathogenic bacteria’s gene expression) was published this year.

French connections

French is one of the working languages of many global health programs, and being able to read documents in their original language has been helpful because many diseases that I care about impact Francophone countries like those in sub-Saharan and west Africa. In one French class, we had to analyze an original primary historical text, so I was able to look at an outbreak of plague in the 18th century and compare their public health response with ours to Covid-19. My MIT French classes have been useful in some very cool ways that I did not anticipate.

Translating medicine for the masses

When I go home and talk about my research, I often adapt folk stories, analogies, and relatable everyday situations to get points across since there might not be exact Patois words or phrases to directly convey what I’m describing. Taking these scientific concepts and breaking them all into bite-size pieces is important for the general American public too. I want to lead a scientific career that not only advances our understanding and treatment of infectious diseases, but also positively impacts policy, education, and outreach. Right now, this looks like a combination of being an academic/medical professor and eventually leading the Centers for Disease Control and Prevention.

Alumni Profile: Matthew Dolan, SB ’81

From Bench to Bedside and Beyond

Lillian Eden | Department of Biology
January 16, 2025

Matthew Dolan, SB ‘81, worked in the U.S. and abroad during a fascinating time in the field of immunology and virology.

In medical school, Matthew Dolan, SB ‘81, briefly considered specializing in orthopedic surgery because of the materials science nature of the work — but he soon realized that he didn’t have the innate skills required for that type of work. 

“I’ll be honest with you — I can’t parallel park,” he jokes. “You can consider a lot of things, but if you find the things that you’re good at and that excite you, you can hopefully move forward with those.” 

Dolan certainly has, tackling problems from bench to bedside and beyond. Both in the U.S. and abroad through the Air Force, Dolan has emerged as a leader in immunology and virology, and has served as Director of the Defense Institute for Medical Operations. He’s worked on everything from foodborne illnesses and Ebola to biological weapons and COVID-19, and has even been a guest speaker on NPR’s Science Friday. 

“This is fun and interesting, and I believe that, and I work hard to convey that — and it’s contagious,” he says. “You can affect people with that excitement.” 

Pieces of the Puzzle

Dolan fondly recalls his years at MIT, and is still in touch with many of the “brilliant” and “interesting” friends he made while in Cambridge. 

He notes that the challenges that were the most rewarding in his career were also the ones that MIT had uniquely prepared him for. Dolan, a Course 7 major, naturally took many classes outside of Biology as part of his undergraduate studies: organic chemistry was foundational for understanding toxicology while studying chemical weapons, while pathogens like Legionella, which causes pneumonia and can spread through water systems like ice machines or air conditioners, are solved at the interface between public health and ecology.

Man sitting on couch next to white dog with pointy ears.
Matthew Dolan stateside with his German Shepherd Sophie. Photo courtesy of Matthew Dolan.

“I learned that learning can be a high-intensity experience,” Dolan recalls. “You can be aggressive in your learning; you can learn and excel in a wide variety of things and gather up all the knowledge and knowledgeable people to work together towards solutions.”

Dolan, for example, worked in the Amazon Basin in Peru on a public health crisis of a sharp rise in childhood mortality due to malaria. The cause was a few degrees removed from the immediate problem: human agriculture had affected the Amazon’s tributaries, leading to still and stagnant water where before there had been rushing streams and rivers. This change in the environment allowed a certain mosquito species of “avid human biters” to thrive.  

“It can be helpful and important for some people to have a really comprehensive and contextual view of scientific problems and biological problems,” he says. “It’s very rewarding to put the pieces in a puzzle like that together.” 

Choosing To Serve

Dolan says a key to finding meaning in his work, especially during difficult times, is a sentiment from Alsatian polymath and Nobel Peace Prize winner Albert Schweitzer: “The only ones among you who will be really happy are those who will have sought and found how to serve.”

One of Dolan’s early formative experiences was working in the heart of the HIV/AIDS epidemic, at a time when there was no effective treatment. No matter how hard he worked, the patients would still die. 

“Failure is not an option — unless you have to fail. You can’t let the failures destroy you,” he says. “There are a lot of other battles out there, and it’s self-indulgent to ignore them and focus on your woe.” 

Lasting Impacts

Dolan couldn’t pick a favorite country, but notes that he’s always impressed seeing how people value the chance to excel with science and medicine when offered resources and respect. Ultimately, everyone he’s worked with, no matter their differences, was committed to solving problems and improving lives. 

Dolan worked in Russia after the Berlin Wall fell, on HIV/AIDS in Moscow and Tuberculosis in the Russian Far East. Although relations with Russia are currently tense, to say the least, Dolan remains optimistic for a brighter future. 

“People that were staunch adversaries can go on to do well together,” he says. “Sometimes, peace leads to partnership. Remembering that it was once possible gives me great hope.” 

Dolan understands that the most lasting impact he has had is, likely, teaching: time marches on, and discoveries can be lost to history, but teaching and training people continues and propagates. In addition to guiding the next generation of healthcare specialists, Dolan also developed programs in laboratory biosafety and biosecurity with the State Department and the Defense Department, and taught those programs around the world. 

“Working in prevention gives you the chance to take care of process problems before they become people problems — patient care problems,” he says. “I have been so impressed with the courageous and giving people that have worked with me.” 

Alumni Spotlight: Distillery Founder with a Spirited Passion

Jennifer Yang, '97, has been drawing on her biology degree for making spirits at a craft distillery in Maryland.

Jessica R. Simpson | Slice of MIT
October 15, 2024

If you had told Jennifer Yang ’97 during her time as a Course 7 major at MIT that she would use her biology degree to run a distillery, she wouldn’t have believed you.

“When I was at MIT, I looked at entrepreneurs and I thought, ‘Oh my gosh, that’s not me. I’m not one of those people who are so innovative and gutsy and brave,’” Yang says.

Managing a distillery is a passion that matured in Yang over time—much like the complex flavor of a barrel-aged whiskey. After graduating from MIT, the New York-native moved to Washington, DC, to pursue a career in management and technology consulting, which involved a lot of after-hours networking events. While building connections with colleagues over a glass of whiskey—a drink that was particularly popular with clients—Yang discovered her passion. Over the course of 10 years, she researched the science of making spirits, explored different small distilleries, and even started a whiskey tasting club.

“Being a science geek at heart and being very curious, I went down this rabbit hole pretty quickly in terms of wanting to learn more about it,” Yang explains.

In November 2022, she and her husband opened Covalent Spirits, a craft distillery, tasting room, and event space in Westminster, Maryland. In addition to producing bourbon whiskey, Covalent Spirits distills and blends vodka, gin, rum, and liqueurs. One of the bar’s unique and in-demand offerings is the “pH,” or “power of hydrogen,” cocktail, which uses the acidity of lemonade to turn a blue tea into a vibrant purple. Yang still works in consulting, but you can find her in her element behind the bar, engineering “pH” (and many other) cocktails Thursday through Saturday.

In her spare time, Yang is a committed MIT volunteer. An active participant in the Club of Washington DC, she is the regional alumni ambassador for the Baltimore area as well. Yang is also an educational counselor and the current president of the Class of 1997. She notes that she and her ’97 classmates were the first to organize pi reunions, a tradition in which alums gather in Las Vegas 3.14 years after graduation. “We’re glad our class could leave a little bit of a legacy,” she says.

In fact, the shared MIT connection between alumni inspired Yang to name her company Covalent Spirits. One year, at an MIT gathering, Yang started talking to another alum about planning events for undergrad classes that shared years at MIT—what they called “covalent classes.” Yang has since incorporated literal and metaphorical covalent bonds (a chemical connection between atoms formed by sharing) into every facet of her business: from the chemistry of making spirits, to the design of the distillery logo, to the company’s emphasis on community.

“While we are striving to create really good products, we also want to create a space and experiences for people to get together and geek out over a common interest, to celebrate an occasion, or to connect over anything,” Yang elaborates. “You share a drink, you share an experience, you share a community. Bonding through sharing is the covalent spirit.”

PNAS Profile: Catherine Drennan

Structural intuitions lead to structural insights

Jennifer Viegas | PNAS
November 8, 2024

HHMI Investigator and Professor of Biology and Chemistry Catherine Drennan has spent a distinguished career addressing challenging and wide-ranging structural biology problems.

Catherine Drennan, a Howard Hughes Medical Institute investigator and professor and a professor of biology and chemistry at the Massachusetts Institute of Technology (MIT), has spent a distinguished career addressing challenging and wide-ranging structural biology problems. These include her discovery, while she was a graduate student, of the structure of vitamin B12 bound to protein and her recent determination at atomic resolution of the structure of an active ribonucleotide reductase (RNR) with water molecules, findings reported in her Inaugural Article (IA) (1).

Drennan, who was elected to the National Academy of Sciences in 2023, has uncovered the form and function of metalloenzymes that use metal cofactors to catalyze chemical reactions involving free radicals. Metalloenzymes are of broad human health and environmental interest; some are promising antibiotic and cancer drug targets, whereas others hold the potential for bioremediation efforts, such as converting carbon dioxide into biofuels.

Family of Accomplished Scientists

Drennan was raised in New York City by her father, an obstetrician–gynecologist, and her mother, an anthropologist. Her father was born in Germany and attended medical school at the University of Hamburg. Harboring antifascist leanings, he fled Germany in 1933. He completed medical training in Geneva, Switzerland, before obtaining political asylum in 1940 in the United States, where he became one of the first doctors to practice the Lamaze Method of natural childbirth.
Drennan’s mother attended Antioch College, where she was a student of civil engineer Arthur Ernest Morgan, who was appointed in 1948 to India’s first University Education Commission. She accompanied Morgan to India and served as his administrative assistant before earning her doctorate in anthropology at Cornell University.

“Both my parents were endlessly curious,” says Drennan. “My father was fascinated by the molecular basis of medicine, and my mother was fascinated by people and instilled in me her love for storytelling, teaching, and mentoring.”

Diagnosed with Dyslexia

Although she was an attentive student, Drennan did not learn to read until her second time through sixth grade. “When I finally learned how to read, it was by memorizing the shapes of words,” says Drennan, who was diagnosed with dyslexia when she was in first grade. “Over time I became very good at shape recognition. I am not disabled; I am differently abled. The skill set that I developed to compensate for my dyslexia has made me a world-class structural biologist. We all have strengths and weaknesses, and my ‘weakness’ is also my superpower.”
She was accepted to Vassar College, where she earned a bachelor’s degree in chemistry in 1985. “Miriam Rossi was my undergraduate chemistry research advisor, and she believed in me before I believed in me,” Drennan says. Upon Rossi’s advice, Drennan pursued a doctorate, but not before teaching high-school science and drama at Scattergood Friends School in Iowa.
Following three years of high-school teaching, Drennan pursued graduate studies at the University of Michigan, Ann Arbor, where she earned a PhD in 1995, served as a research fellow from 1995 to 1996, and was mentored by biochemists Martha Ludwig and Rowena Matthews. “They treated me as a colleague, allowing me to see myself as a scientist of value,” Drennan says. “I learned so much from these two incredible scientists. They are, and always will be, my heroes.”

Structure of Vitamin B12 Bound to Protein

With Ludwig et al., Drennan determined the structure of cobalamin (vitamin B12) bound to protein (2). This crystal structure revealed how the protein modulates the reactivity of the B12 cofactor to enable its critical roles in metabolism.
From 1996 to 1999, Drennan did a postdoctoral stint at the California Institute of Technology, under the mentorship of structural biologist Douglas Rees. “Doug taught by example that one does not have to be cutthroat to succeed in the competitive area of structural biology,” she says. “He has continued to mentor me throughout my career, helping me through challenging times.”
Another important mentor was chemist JoAnne Stubbe, a leader in the study of RNRs who recruited Drennan to MIT in 1999 as an assistant professor of chemistry and has been her collaborator for the past 25 years. Drennan says, “Her passion for scientific discovery is unmatched and has inspired me to keep digging to try to understand, at the most fundamental level, how ribonucleotide reductase works.” Drennan advanced to an associate professorship at MIT in 2004 and a full professorship in 2006.

Revealing Metalloenzyme Form and Function

Drennan’s group continues to study B12 and has provided numerous snapshots of cobalamin-dependent proteins and protein complexes. The findings have changed what is known about B12 functions and mechanisms. Using X-ray crystallography, the researchers unveiled a protein complex capable of methyl transfer from folate to B12 (3). They obtained snapshots of the biological process involved in loading B12 into an enzyme (4) and provided structural data on how B12 can be repurposed from enzyme cofactor to light sensor (5).
Drennan has also worked on uncovering the structures of enzymes containing radical S-adenosylmethionine (SAM) cofactors. Drennan and colleagues revealed an X-ray structure of a radical SAM enzyme (6), helping to establish the “core” fold for an enzyme superfamily that has over 100,000 members. Her group further elucidated structures of SAM family members with functions including posttranslational modification (7), antibiotic and antiviral compound biosynthesis (8, 9), and vitamin biosynthesis (6, 10).
Mononuclear nonheme iron enzymes are also of interest to Drennan. The cofactor is simple, but the reactions catalyzed are complex. Her group reported the structure of a nonheme iron halogenase, showing that the halogen binds directly to the catalytic iron (11). Drennan says, “This was a complete surprise that required new mechanistic proposals to be written.”

“Oceanic Methane Paradox”

Early in her independent career, Drennan determined one of the first structures of a nickel-iron-sulfur-dependent carbon monoxide dehydrogenase (CODH), which plays an important role in the global carbon cycle (12). The structure, along with that of an associated enzyme complex (13), provided a series of snapshots of the multiple metal ion centers underlying the ability of certain microbes to live off hydrogen gas and carbon dioxide in a process known as acetogenesis. More recently, they investigated the molecular basis by which the activity of CODH enzymes can be restored after oxygen exposure (14), a discovery with implications for the industrial use of CODHs.
Drennan and her team have also studied the organic compound methylphosphonate that was proposed as a source of methane from the aerobic upper ocean; the biological source was long a mystery. When a methylphosphonate synthase was discovered by chemical biologist Wilfred van der Donk and coworkers, part of the mystery was solved but the gene for this enzyme did not appear to be widespread. When Drennan and colleagues solved the structure of a methylphosphonate synthase; however, they discovered a sequence motif showing that the gene was, in fact, abundant in microbes that inhabit the upper ocean (15). This seminal finding is credited with resolving the oceanic methane paradox.

Radical-Based Chemistry in Ribonucleotide Reductases

Human RNR is an established chemotherapeutic target, and bacterial RNRs hold promise as antibiotic targets. So Drennan and her team have a longstanding interest in uncovering the mechanisms of RNRs. In 2002, her lab determined the structure of a B12-dependent RNR, which showed how cobalamin could be used to initiate radical chemistry (16). Nearly a decade later, Drennan’s team revealed how high levels of the nucleotide deoxyadenosine triphosphate (dATP) down-regulate RNR activity (17, 18). They subsequently provided structures showing the molecular basis of allosteric specificity, which maintains the proper ratios of RNA to DNA building blocks (19), and demonstrated the importance of RNR activity regulation (20).
An atomic-resolution structure of any RNR in an active state had been elusive for many years. Drennan and her team achieved the feat in 2020 when they trapped the active state of Escherichia coli RNR and determined its structure by cryoelectron microscopy (21). However, the resolution of the structure was too low for the visualization of water molecules believed to be critical in the radical transfer pathway.
In her IA, Drennan (1) describes how her team resolved the problem, presenting the structure of an active RNR at atomic resolution allowing for the visualization of water molecules. She explains, “This time, instead of using unnatural amino acids to trap the structure, we used a mechanism-based inhibitor. It was a very long road to get to these data, but it was worth the wait.”

“Superheroes of the Cell”

For her achievements, Drennan has received MIT’s Everett Moore Baker Memorial Award for Excellence in Undergraduate Teaching (2005, 2024), the Dorothy Crowfoot Hodgkin Award from The Protein Society (2020), and the William C. Rose Award from the American Society for Biochemistry and Molecular Biology (2023), among other honors. She has mentored nearly 100 undergraduates and dozens of graduate students and postdoctoral associates, many of whom are from underrepresented minority groups or disadvantaged backgrounds. She considers her students extended family members and takes pride in their accomplishments.
She and her team continue to work on RNR using the tools of structural biology. She says, “We want to obtain a deeper level of understanding of the human RNR, which is a cancer drug target. We also want to identify differences between the human enzyme and bacterial RNRs, differences that could be exploited in the development of new antibiotics.”
Beyond these efforts, Drennan’s overall goal is to understand how enzymes control radical species to enable challenging chemical reactions without damaging themselves or their cellular environment. “Radical enzymes are like the Avengers, powerful but with a high potential for collateral damage,” she explains. “I am fascinated by how nature catalyzes the most challenging of chemical reactions. The enzymes that do this work are the superheroes of the cell and I want to know their secrets.”
1.
D. E. Westmoreland et al., 2.6-Å resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N3CDP. Proc. Natl. Acad. Sci. U.S.A. 121, e2417157121 (2024). Crossref. PubMed.
2.
C. L. Drennan et al., How a protein binds B12: A 3.0 Å X-ray structure of B12-binding domains of methionine synthase. Science 266, 1669–1674 (1994). Crossref. PubMed.
3.
Y. Kung et al., Visualizing molecular juggling within a B12-dependent methyltransferase complex. Nature 484, 265–269 (2012). Crossref. PubMed.
4.
F. A. Vaccaro, D. A. Born, C. L. Drennan, Structure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery. Proc. Natl. Acad. Sci. U.S.A. 120, e2214085120 (2023). Crossref. PubMed.
5.
M. Jost et al., Structural basis for gene regulation by a B12-dependent photoreceptor. Nature 526, 536–541 (2015). Crossref. PubMed.
6.
F. Berkovitch et al., Crystal structure of biotin synthase, an S-Adenosylmethionine-dependent radical enzyme. Science 303, 76–79 (2004). Crossref. PubMed.
7.
J. L. Vey et al., Structural basis for glycyl radical formation by pyruvate formate-lyase activating enzyme. Proc. Natl. Acad. Sci. U.S.A. 105, 16137–16141 (2008). Crossref. PubMed.
8.
J. Bridwell-Rabb et al., A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis. Nature 544, 322–326 (2017). Crossref. PubMed.
9.
P. J. Goldman, T. L. Grove, S. J. Booker, C. L. Drennan, X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry. Proc. Natl. Acad. Sci. U.S.A. 40, 15949–15954 (2013). Crossref.
10.
M. I. McLaughlin et al., Crystallographic snapshots of sulfur insertion by lipoyl synthase. Proc. Natl. Acad. Sci. U.S.A. 113, 9446–9450 (2016). Crossref. PubMed.
11.
L. C. Blasiak, F. H. Vaillancourt, C. T. Walsh, C. L. Drennan, Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature 440, 368–371 (2006). Crossref. PubMed.
12.
C. L. Drennan et al., Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase. Proc. Natl. Acad. Sci. U.S.A. 98, 11973–11978 (2001). Crossref. PubMed.
13.
T. I. Doukov et al., A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase. Science 298, 567–572 (2002). Crossref. PubMed.
14.
E. C. Wittenborn et al., Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide dehydrogenase. Elife 7, e39451 (2018). Crossref. PubMed.
15.
D. A. Born et al., Structural basis for methylphosphonate biosynthesis. Science 358, 1336–1339 (2017). Crossref. PubMed.
16.
M. D. Sintchak et al., The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer. Nat. Struct. Mol. Biol. 9, 293–300 (2002). Crossref.
17.
N. Ando et al., Structural interconversions modulate activity of Escherichia coli ribonucleotide reductase. Proc. Natl. Acad. Sci. U.S.A. 108, 21046–21051 (2011). Crossref. PubMed.
18.
N. Ando et al., Allosteric inhibition of human ribonucleotide reductase by dATP entails the stabilization of a hexamer. Biochemistry 55, 373–381 (2016). Crossref. PubMed.
19.
C. M. Zimanyi et al., Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli. Elife 5, e07141 (2016). Crossref. PubMed.
20.
P.Y.-T. Chen, M. A. Funk, E. J. Brignole, C. L. Drennan, Disruption of an oligomeric interface prevents allosteric inhibition of Escherichia coli class Ia ribonucleotide reductase. J. Biol. Chem. 293, 10404–10412 (2018). Crossref. PubMed.
21.
G. Kang, A. T. Taguchi, J. Stubbe, C. L. Drennan, Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex. Science 368, 424–427 (2020). Crossref. PubMed.
BSG-MSRP-Bio Student Profile: Adriana Camacho-Badillow, Calo Lab

Understanding the Role of PARPs and UBF1 in Building Ribosomes

Noah Daly | Department of Biology
September 25, 2024

While pursuing her passion for research, BSG-MSRP-Bio student Adriana Camacho-Badillo made major contributions to research in the Calo Lab in the Department of Biology at MIT.

Growing up in Puerto Rico, Adriana Camacho-Badillo had no explanation for her recurrent multiple fracture injuries. In her teens, she was finally able to see a geneticist who diagnosed her with a genetic syndrome that affects connective tissue throughout the body. 

This awakened an interest in genetics that led her to immerse herself in her genetic panel results, curious about the role of each gene that was tested. 

“I realized I wanted to find out how mutations affect gene expression that could possibly lead to a distinct phenotype or even a genetic syndrome,” she says. 

Within a few years of setting her sights on becoming a scientist, Camacho-Badillo began her first research experience working in the laboratory of Professors Hector Areizaga-Martínez and Elddie Román-Morales. Her work focused on experiments using enzymes to degrade Dichloro-diphenyl-trichloroethane, or DDT, a once-common pesticide known to be highly toxic to humans and other mammals that remains in the environment long after application to crops. 

As she became familiar with the day-to-day routines of designing and executing research experiments, she realized she was drawn to biochemistry and molecular biology. Camacho-Badillo soon applied to the molecular neuroscience lab of Professor Miguel Méndez at the University of Puerto Rico at Aguadilla and joined their team working on the effects of high glucose in the central nervous system of mice.

Expanding Experiences While Narrowing Focus

When Camacho-Badillo was sixteen, alongside Méndez and other students, she participated in the Quantitative Methods Workshop at MIT. The workshop allows undergraduate students from universities around the United States and the Caribbean to come together for a few days in January to learn how to apply computational tools that can help biological research. 

One of the sessions she attended was a talk about machine learning and studying the brain, presented by graduate student Taylor Baum. 

“I loved Taylor’s workshop,” Camacho-Badillo said, “When Taylor asked if anyone would be interested in volunteering to teach Spanish-speaking students in grade school science, I said yes without hesitation.” 

Baum, a neuroscientist and computer scientist working in the Munther Dahleh Research Group at MIT, is also the founder of Sprouting, Inc. The organization equips high-school students and undergraduates in Puerto Rico with STEM skills to help them pursue careers in science and technology.

After participating in QMW, it wasn’t long before Camacho-Badillo was back at MIT. She participated in the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology in 2023 and worked in the Yamashita Lab, studying two phenotypes of genetic mutations associated with cancer during cell division. 

The BSG-MSRP-Bio program offers lab experience and extracurricular activities such as journal clubs and dinners with professors. At one of these events, she met Associate Professor of Biology Eliezer Calo.

Camacho-Badillo and her mentor Eliezer Calo, Associate Professor of Biology. Photo Credit: Mandana Sassanfar.

“I loved meeting another scientist from Puerto Rico working on molecular biology, so I decided to look further into his research,” Camacho-Badillo recalls. 

In 2024, she was delighted to have the opportunity to return to the BSG-MSRP-Bio Program for a second time, and now to work in Calo’s Lab. 

The Unsolved Mysteries of UBF1

Although BSG-MSRP-Bio students are often mentored by graduate students or postdocs, Calo spent the summer mentoring Camacho-Badillo directly. As an alumnus of the MSRP-Bio program himself, Calo understands firsthand how much of an impact meaningful research can have for an undergraduate student spending a few months experiencing life in the lab at MIT. 

In the Calo Lab, Camacho-Badillo spent the early days of this summer poring over past research papers on genetic transcription, trying to answer a big question in molecular biology. Camacho-Badillo has been helping Calo understand how a particular protein affects the production of ribosomes in cells.

A ribosome is the molecular machinery that synthesizes proteins, and an average cell can produce around 10 million ribosomes to sustain its essential functions. Creating these protein engines requires the transcription of ribosomal DNA, or rDNA. 

In order to synthesize RNA, specific proteins called polymerases must bind to the DNA. Camacho-Badillo’s work focuses on one of those binding proteins called upstream binding factor, or UBF1. UBF1 is essential for the synthesis of the ribosomal RNA. The UBF1 transcription factor is responsible for recruiting the polymerase, RNA polymerase I, to transcribe the rDNA into rRNA.

Despite knowing the importance of UBF1 in ribosomal production, it’s unclear what its full purpose is in this process. Calo and Camacho-Badillo think that clarifying the role of UBF1 in ribosomal biogenesis will help scientists understand how certain neurological diseases occur. UBF1 is known to be associated with diseases such as acute myeloid leukemia and childhood-onset neurodegeneration with brain atrophy, but the mechanism is not yet understood.

UBF1 is a peculiar transcription factor. Before it can transcribe a gene, UBF1 must first dimerize, forming a bond with another UBF1 protein. After binding to the rDNA, UBF1 can recruit the remaining RNA transcription machinery. The dimer is crucial for transcription to occur, yet this protein can make further connections with other UBF1 monomers, a process called oligomerization. 

Nothing is concretely understood about how oligomers of UBF1 form: they could be critical for transcription, forming clusters that can no longer bind with rDNA or inhibit the recruitment of the remaining RNA transcription machinery. These clusters could also be directly contributing to a variety of neurological diseases.

“The genome contains multiple rDNA copies, but not all are utilized,” Calo explains. “UBF1 must precisely identify the correct copies to activate while avoiding the formation of aggregates that could impair its function.”

The regulation of these dimers is also a mystery. Early in the summer, Camacho-Badillo helped make an important connection: prior research from the Calo Lab showed that enzymes called poly ADP-ribose polymerases, or PARPs, play a role in maintaining chemical properties in the nucleolus, where ribosomes are produced and assembled. The main target of these proteins within the RNA transcriptional machinery before transcription is initiated is UBF1.  

Based on this initial result, Camacho-Badillo’s entire summer project shifted to further characterize PARPs in ribosome biogenesis.

“This observation about the role PARPs plays is a big deal for us,” Calo says. “We do many experiments in my lab, but Adriana’s work this summer has opened a key gateway to understanding the mysteries behind UBF1 regulation, leading to proper ribosome production and allowing the Calo lab to pursue this goal. She’s going to be a superstar.” 

Camacho-Badillo’s work hasn’t ended with the BSG-MSRP-Bio program, however. She’ll spend the fall semester at MIT, continuing to work on understanding how rDNA transcription is regulated as a visiting student in the Calo Lab. Although she still has a year and a half to go in her undergraduate degree, she’s already set her sights on graduate school. 

“This program has meant so much to me and brought so much into my life,” she says. “All I want to do right now is keep this research going.”

Want to know more about our BSG-MSRP-Bio Students? Read more testimonials and stories here.