Category: Profiles

Boston Globe: Mary-Lou Pardue, MIT professor whose anti-bias efforts lifted women in science, dies at 90

Her research formed the foundation for understanding the structure of chromosomes.

Bryan Marquard | Boston Globe
July 7, 2024

Amid the clatter of lunchtime dishes, Mary-Lou Pardue sat across from Nancy Hopkins one day in 1994 in a café not far from the Massachusetts Institute of Technology, reading a letter Hopkins had drafted.

Both were MIT professors and scientists, and Hopkins, the younger of the two, had gathered data showing women on the faculty were routinely discriminated against in numerous ways. Hopkins wanted to send her findings to the school’s president, but sought a blessing of sorts from Dr. Pardue, the first woman in MIT’s School of Science to be inducted into the National Academy of Sciences.

“I chose Mary-Lou as the person whose judgment would mean the most to me. I had this huge respect for her as a scientist before I even met her,” Hopkins recalled in an interview.

Dr. Pardue read the letter “very slowly and put it down on the table and said, ‘I agree with this letter, every word. I want to sign it and think you should send it to the president,’ ” Hopkins said. “And that changed my life, and ultimately it changed MIT. That was, to me, the defining moment for women at MIT.”

A highly regarded cellular and molecular biologist whose work formed the foundation for key advancements and discoveries in understanding the structure of chromosomes, Dr. Pardue died June 1 in Youville Assisted Living in Cambridge.

She was 90, had been diagnosed with Parkinson’s disease, and her health had been failing.

The first Boris Magasanik professor of biology at MIT, Dr. Pardue had also been an American Academy of Arts and Sciences fellow, and was a past president of the Genetics Society of America and the American Society for Cell Biology.

Her efforts at MIT 30 years ago with Hopkins and other female professors, however, are still having a ripple effect through academia across the country and around the world.

When Dr. Pardue told Hopkins she wanted to sign the letter about bias against women and send it to MIT’s president, “I knew the world had shifted,” said Hopkins, whose efforts with Dr. Pardue and others were documented in “The Exceptions,” a 2023 book by New York Times reporter Kate Zernike, who initially broke the story as a Boston Globe reporter.

“I could sense the power of it: Two women, saying the same thing, one of them a member of the National Academy of Sciences,” Hopkins said. “She looked at me and felt the same thing, that two women together had power.”

They reached out to other tenured female professors at MIT, and almost all co-signed the letter, which they presented to the president. In 1995, MIT created the Committee on the Status of Women Faculty, whose 1999 report documented the systematic bias that women in the School of Science were facing.

That report, and MIT’s subsequent efforts to address its failings, led to similar efforts at universities across the country.

“It was life-changing, but that it could change the world? This is not something that occurred to me then,” Hopkins said, laughing at the memory.

As a young scientist, Dr. Pardue and Joseph Gall, who had been her doctoral adviser at Yale University, developed an “in situ hybridization” technique that “led to many discoveries, including critical advancements in developmental biology, our understanding of embryonic development, and the structure of chromosomes,” MIT said in its tribute to Dr. Pardue.

“In situ hybridization was a crucial step toward genomics. In some ways you could call it the first genomic technique,” said Allan Spradling, an investigator at the Howard Hughes Medical Institution.

“Her research is underappreciated,” said Spradling, who also is a former director of the embryology department at the Carnegie Institution for Science. “It’s all tied into so many momentous events in the history of genomics.”

Kerry Kelley, who formerly managed Dr. Pardue’s lab, and is now manager of the Yilmaz Lab at the Koch Institute for Integrative Cancer Research, said that “Mary-Lou was a giant of her time.”

Continuing to work in her lab after the onset of Parkinson’s, Dr. Pardue was “gracious, kind, smart as a whip, and just full of great stories,” Kelley said.

The techniques that Dr. Pardue and Gall developed are now used in thousands of labs around the world, said Thomas Cech, a former post-doctoral student of Dr. Pardue’s who shared the 1989 Nobel Prize in Chemistry.

“It was one of those discoveries which seemed important at the time and certainly attracted many of us to her laboratory,” he said, “but in retrospect, we had no idea how powerful this would become.”

Born on Sept. 15, 1933, Mary-Lou Pardue grew up in and around Lexington, Ky.

Her father, Louis Pardue, was a dean at Virginia Tech. Her mother, Mary Allie Marshall Pardue, had been a teacher before marrying. Her younger brother, William, who died in 2016, was a scientist in the nuclear industry.

Dr. Pardue graduated in 1955 from the College of William and Mary with a bachelor’s degree in biology.

After working in research, she received a master’s in radiation biology in 1959 from the University of Tennessee and a doctorate in biology in 1970 from Yale University.

She also did postdoctoral work at the University of Edinburgh before seeking a faculty position in the United States. MIT turned her down with a letter at first, and then recruited her for an associate professor position in 1972 after hearing about her work and lectures, “which I thought was as sincere an apology as you can get,” she said with a laugh in a video forum that MIT posted online.

Dr. Pardue, whose marriage in her graduate student years ended in divorce, was an avid hiker in New Hampshire’s White Mountains who also took on distant challenging terrain. She agreed to the Genetics Society presidency because on the way home from an international meeting in India she could go trekking in Nepal’s Annapurna range.

“She was a fun person to be around,” said Susan A. Gerbi, the George Eggleston professor of biochemistry emerita at Brown University, and a graduate school contemporary of Dr. Pardue’s at Yale.

“She had a twinkle in her eye, which you can see even if you look at the seminar she gave on YouTube,” Gerbi said. “And she was very smart and had good insights.”

Over the years, Dr. Pardue was close to her brother’s family, spending time with them during the winter holidays and going along on skiing and camping trips.

“A lot of times you run into scientists who are quite intelligent and can’t relate to people on a personal level,” said her nephew, Todd Pardue of Fairfax Station, Va. “She would take the time to talk to you. She was a very special person.”

He and his sister, Sara Pardue Gibson of Columbus, Ohio, are their aunt’s closest survivors. Plans for a celebration of Dr. Pardue’s life and work are pending.

While fielding questions during her MIT talk that was recorded for a video, Dr. Pardue smiled and said in a voice still rich with the Kentucky accent of her youth that as a researcher, “the greatest joy is when an experiment you didn’t think would work, works.”

Such clear, concise lessons were among those she imparted to generations of young scientists who worked in her labs, including at MIT, where she was a professor for more than 30 years.

“She was a great mentor who was as proud of her scientific children and grandchildren as she was of her own accomplishments. That’s not the way all scientists look at things,” said Ky Lowenhaupt, manager of the Biophysical Instrumentation Facility at MIT.

Lowenhaupt said Dr. Pardue “was a role model of what women in science can be at a time when there weren’t a lot of those, and a trailblazer as a woman — but also a trailblazer as a scientist who didn’t do things along the path that other people took.”

A day in the life — graduate student and genomics researcher Neha Bokil

Neha Bokil is studying mechanisms that regulate expression of genes located on the X and Y chromosomes in order to better understand sex-biased conditions that predominantly affect one sex.

Shafaq Zia | Whitehead Institute
June 25, 2024

Graduate student Neha Bokil moves around the Page lab with urgency. Today, she’s running an experiment using white blood cells from patients with varying numbers of X and Y chromosomes.

The lab of Whitehead Institute Member David Page investigates the role of the X and Y chromosomes beyond determining sex. While most females have two X chromosomes (XX) and most males have one X and one Y chromosome (XY), there are individuals whose sex chromosome constitution varies from this, having instead, for example, XXY, XXX, or XXXXY. With the goal of understanding why certain conditions are more prevalent in one sex versus than the other, Bokil is using this experiment to explore if and how cellular processes, such as gene regulation, vary among individuals with these atypical combinations of sex chromosomes.

Partially hidden in the cell culture hood, Bokil finally locates what she’s been searching for: a pipette for dispensing 99 microliters of the cell suspension she’s meticulously prepared this afternoon, a type of culture where cells float in nutrient-rich liquid, free to function and grow.

Bokil carefully extracts this volume and transfers it to a flat plate — also called a 96-well plate — with tiny holes for growing small cell samples. Now, it’s a waiting game until she can find out how these cells are growing, and whether their proliferation rate depends on the number of sex chromosomes in a cell.

Bokil dives into the intricacies of human genetics every day, hoping her work will eventually help reshape how sex differences are understood in medicine and improve treatment outcomes. The dynamic research Bokil is conducting at Whitehead Institute is her calling, but she has other passions as well. Here’s what a typical day in her life as a graduate student looks like, both in and outside the lab.

An inherited love of numbers

When she isn’t rushing out the door, Bokil loves brewing and savoring the perfect cup of morning chai, a traditional South Asian loose-leaf tea with milk. Every family has their own recipe, and Bokil makes hers with ginger, a touch of cardamom, and some sugar.

“Chai is comforting at any time, but I’ve noticed my mood vastly improves when I’m able to have a cup in the morning,” she says.

On her walk to the Whitehead Institute, she often listens to Bollywood songs. But these predilections — chai and Indian cinema — are more than just rituals for her. They symbolize tradition and cherished connections with family and friends.

In fact, family bonds have greatly influenced Bokil’s career path. As a child, she loved mathematics. It wasn’t a trait passed on genetically, but one that flourished through moments of connection with her grandmother, a math teacher in India. During summer visits to Bokil’s family in the U.S., she’d enthusiastically impart her passion for numbers onto her granddaughter. By the time Bokil went to high school and later college, she had become fluent in the language of logic and patterns.

“My time with her made me realize just how beautiful and fun math is, and I could see its practical applications in everyday life, all around me,” Bokil says.

For her PhD, she sought to combine her undergraduate training in mathematics and molecular biology to tackle a real-world problem. With genetics at the crossroads of these disciplines, and the Page Lab leading the way in transforming scientific understanding of X and Y chromosomes beyond reproduction, Bokil knew she had to get involved.

This morning, as she sits at her desk, poring over a research paper before an afternoon lab meeting, she ponders how insights from the study could enhance her manuscript writing process. Bokil’s graduate project uses a collection of cell lines derived from patients with atypical numbers of X and Y chromosomes to investigate mechanisms that regulate — or dial up and down the expression of — genes located on one of the X chromosomes in females called the “inactive” X chromosome.

Although the X and Y sex chromosomes in mammals began as a pair with similar structures, over time, the Y chromosome underwent degeneration, leading to the loss of numerous active genes. In contrast, the X chromosome preserved its original genes and even gained new ones. To maintain balance in gene expression across the two sexes — XX and XY — an evolutionary mechanism called X chromosome inactivation emerged.

This process is known to randomly silence one X chromosome in each XX pair, ensuring that both sexes have an equal dosage of genes from the X chromosome. However, in recent years, the Page lab has discovered that there are powerful distinctions within females’ pair of X chromosomes, and the so-called “inactive” X chromosome is far from passive. Instead, it plays a crucial role in regulating gene expression on the active X chromosome.

“That’s not all,” adds Bokil. “There are still genes expressed from that “inactive” X chromosome. Cracking how these genes are regulated could answer longstanding questions about sex differences in health.”

Bokil is unraveling this genetic mystery with the help of chemical tags called histone marks. These tags cling to a family of proteins that function like spools, allowing long strands of DNA to coil around them — like thread around a bobbin — so genetic information remains neatly packaged within the cell’s nucleus.

This complex of DNA, RNA, and proteins is called chromatin, the genetic material that eventually forms chromosomes. Chromatin also lays the groundwork for gene regulation by keeping some genes tightly wound around the histones, rendering them inaccessible, and unwinding others for active use.

Certain histone marks are associated with open chromatin structure and active gene expression, while others indicate closed chromatin structure and gene silencing. By examining the specific histone marks on proteins near genes on the “inactive” X chromosome, Bokil aims to decipher if and how these genes are turned on and off.

She’s particularly interested in a group of genes that have counterparts on the Y chromosome. These genes, known as homologous X-Y gene pairs, are typically dosage-sensitive and play a crucial role in regulating essential processes throughout the body like the transcription of DNA into RNA and the translation of RNA into proteins.

Celebrating small triumphs

Graduate school can feel like a marathon — progress is slow but every small step counts towards a breakthrough. For Bokil, stumbling upon a captivating scientific puzzle has been a stroke of luck she deeply appreciates. In fact, the mystery of how genes are controlled on the “inactive” X chromosome has not only shaped her scientific pursuits but also her artwork — on one quiet evening at home, she found herself inspired to capture an experiment, called CUT&RUN, in her painting.

During the early days of her PhD, Bokil spent hundreds of hours using this technique to identify the precise locations of histone protein and DNA interactions. Right as she was prepared to expand these experiments across multiple cell lines, the COVID-19 hit, throwing her plans — and progress — off course.

During these challenging times, Bokil found solace in her cultural roots and the warmth of community. She began teaching virtual BollyX classes — a dance similar to Zumba, but on Bollywood tunes — every Tuesday evening as a means to stay connected, a commitment she’s upheld ever since throughout her time in graduate school.

Beyond nurturing a sense of togetherness through dance, Bokil is committed to mentoring in science and celebrating improbable victories along a tedious research journey.

“I had a former lab mate who used to do what she called a data dance every time she had a graph she felt happy with,” Bokil recalls. “I think that should catch on a little bit more because it’s always a really good feeling to see how these experiments that have taken up so much of your time and effort are leading somewhere.”

In Memoriam: Mary-Lou Pardue, 1933-2024

Mary-Lou Pardue, Professor Emeritus of Biology, dies at 90

Lillian Eden | Department of Biology
June 17, 2024

Known for her rigorous approach to science and pioneering research, Pardue paved the way for women scientists at MIT and beyond

Mary-Lou Pardue, professor emerita in the Department of Biology, died on June 1, 2024. She was 90.

Early in her career, Pardue developed a technique called in situ hybridization with her PhD advisor Joseph Gall, which allows researchers to localize genes on chromosomes. This led to many discoveries, including critical advancements in developmental biology, our understanding of embryonic development, and the structure of chromosomes. She also studied the remarkably complex way organisms respond to stress, such as heat shock, and discovered how telomeres, the ends of chromosomes, in fruit flies differ from those of other eukaryotic organisms during cell division.

“The reason she was a professor at MIT and why she was doing research was first and foremost because she wanted to answer questions and make discoveries,” says longtime colleague and Professor Emerita Terry Orr-Weaver. “She had her feet cemented in a love of biology.”

In 1983, Pardue was the first woman in the School of Science at MIT to be inducted into the National Academy of Sciences. She served as Chairman for the Section of Genetics from 1991 to 1994 and as a Council Member from 1995 to 1998. Among other honors, she was named a Fellow of the American Academy of Arts and Sciences, where she served as a Council Member, and a Fellow of the American Association for the Advancement of Science.  She also served on numerous editorial boards and review panels, and as the vice president, president, and chair of the Genetics Society of America and president of the American Society for Cell Biology.

Her graduate students and postdoctoral scholars included Alan Spradling, Matthew Scott, Tom Cech, Paul Lasko, and Joan Ruderman.

In the minority

Pardue was born on Sept. 15, 1933, in Lexington, Kentucky. She received a BS in Biology from the College of William and Mary in 1955, and she was awarded an MS in Radiation Biology from the University of Tennessee in 1959. In 1970, she was awarded a PhD in Biology for her work with Gall at Yale University.

As one of the senior women faculty who co-signed a letter to the Dean of Science at MIT about the bias against women scientists at the institute, Pardue’s career was inextricably linked to the slowly rising number of women with advanced degrees in science. During her early years as a graduate student at Yale, there were a few women with PhDs — but none held faculty positions. Indeed, Pardue assumed she would spend her career as a senior scientist working in someone else’s lab, rather than running her own.

Pardue was an avid hiker and loved to travel and spend time outdoors. She scaled peaks from the White Mountains to the Himalayas and pursued postdoctoral work in Europe at the University of Edinburgh. She was delighted to receive invitations to give faculty search seminars for the opportunity to travel to institutions across the U.S.—including an invitation to visit MIT.

MIT had initially rejected her job application, although the department quickly realized it had erred in missing the opportunity to recruit Pardue. In the end, she spent more than 30 years as a professor in Cambridge.

When Pardue joined, the department had two women faculty members, Lisa Steiner and Annamaria Torriani-Gorini — more women than at any other academic institution Pardue had interviewed. Pardue became an associate professor of Biology in 1972, a professor in 1980, and the Boris Magasanik Professor of Biology in 1995.

The person who made a difference

Pardue was known for her rigorous approach to science as well as her bright smile and support of others.

When Graham Walker, American Cancer Society and HHMI Professor, joined the department in 1976, he recalled an event for meeting graduate students at which he was repeatedly mistaken for a graduate student himself. Pardue parked herself by his side to bear the task of introducing the newest faculty member.

“Mary-Lou had an art for taking care of people,” Walker says. “She was a wonderful colleague and a close friend.”

Troy Littleton, Professor of Biology, Menicon Professor of Neuroscience, and Investigator at the Picower Institute for Learning and Memory — then a young faculty member — had his first experience teaching with Pardue for an undergraduate project lab course.

“Observing how Mary-Lou was able to get the students excited about basic research was instrumental in shaping my teaching skills,” Littleton says. “Her passion for discovery was infectious, and the students loved working on basic research questions under her guidance.”

She was also a mentor for fellow women joining the department, including E.C. Whitehead Professor of Biology and HHMI investigator Tania A. Baker, who joined the department in 1992, and Orr-Weaver, the first female faculty member to join the Whitehead Institute in 1987.

“She was seriously respected as a woman scientist—as a scientist,” recalls Nancy Hopkins, Amgen Professor of Biology Emerita. “For women of our generation, there were no role models ahead of us, and so to see that somebody could do it, and have that kind of respect, was really inspiring.”

Hopkins first encountered Pardue’s work on in situ hybridization as a graduate student. Although it wasn’t Hopkins’ field, she remembers being struck by the implications — a leap in science that today could be compared to the discoveries that are possible because of the applications of gene-editing CRISPR technology.

“The questions were very big, but the technology was small,” Hopkins says. “That you could actually do these kinds of things was kind of a miracle.”

Pardue was the person who called to give Hopkins the news that she had been elected to the National Academy of Sciences. They hadn’t worked together, yet, but Hopkins felt like Pardue had been looking out for her, and was so excited on her behalf.

Later, though, Hopkins was initially hesitant to reach out to Pardue to discuss the discrimination Hopkins had experienced as a faculty member at MIT — Pardue seemed so successful that surely her gender had not held her back. Hopkins found that women, in general, didn’t discuss the ways they had been undervalued; it was humiliating to admit to being treated unfairly.

Hopkins drafted a letter about the systemic and invisible discrimination she had experienced — but Hopkins, ever the scientist, needed a reviewer.

At a table in the corner of Rebecca’s Café, a now-defunct eatery, Pardue read the letter — and declared she’d like to sign it and take it to the Dean of the School of Science.

“I knew the world had changed in that instant,” Hopkins says. “She’s the person who made the difference. She changed my life, and changed, in the end, MIT.”

MIT and the status of women

It was only when some of the tenured women faculty of the School of Science all came together that they discovered their experiences were similar. Hopkins, Pardue, Orr-Weaver, Steiner, Susan Carey, Sylvia Ceyer, Sallie “Penny” Chisholm, Suzanne Corkin, Mildred Dresselhaus, Ann Graybiel, Ruth Lehmann, Marcia McNutt, Molly Potter, Paula Malanotte-Rizzoli, Leigh Royden, and Joanne Stubbe ultimately signed a letter to Robert Birgeneau, then the Dean of Science.

Their efforts led to a Committee on the Status of Women Faculty in 1995, the report for which was made public in 1999. The report captured pervasive bias against women across the School of Science. In response, MIT ultimately worked to improve the working conditions of women scientists across the institute. These efforts reverberated at academic institutions across the country.

Walker notes that creating real change requires a monumental effort of political and societal pressure — but it also requires outstanding individuals whose work surpasses the barriers holding them back.

“When Mary-Lou came to MIT, there weren’t many cracks in the glass ceiling,” he says. “I think she, in many ways, was a leader in helping to change the status of women in science by just being who she was.”

Later years

Kerry Kelley, now a research laboratory operations manager in the Yilmaz Lab at the Koch Institute for Integrative Cancer Research, joined Pardue as a technical lab assistant in 2008, Kelley’s first job at MIT. Pardue, throughout her career, was committed to hands-on work, preparing her own slides whenever possible.

“One of the biggest things I learned from her was mistakes aren’t always mistakes. If you do an experiment, and it doesn’t turn out the way you had hoped, there’s something there that you can learn from,” Kelley says. She recalls a frequent refrain with a smile: “‘It’s research. What do you do? Re-search.’”

Their birthdays were on consecutive days in September; Pardue would mark the occasion for both at Legal Seafoods in Kendall Square with Bluefish, white wine, and lab members and collaborators including Kelley, Karen Traverse, and the late Paul Gregory DeBaryshe.

In the years before her death, Pardue resided at Youville House Assisted Living in Cambridge, where Kelley would often visit.

“I was sad to hear of the passing of Mary-Lou, whose seminal work expanded our understanding of chromosome structure and cellular responses to environmental stresses over more than three decades at MIT. Mary-Lou was an exceptional person who was known as a gracious mentor and a valued teacher and colleague,” says Biology Department Head and Jay A. Stein (1968) Professor of Biology and Professor of Biological Engineering Amy Keating. “She was kind to everyone, and she is missed by our faculty and staff. Women at MIT and beyond, including me, owe a huge debt to Mary-Lou, Nancy Hopkins, and their colleagues who so profoundly advanced opportunities for women in science.”

She is survived by a niece and nephew, Todd Pardue and Sarah Gibson.

Alum Profile: Gevorg Grigoryan, PhD ’07

Creating the Crossroads

Lillian Eden | Department of Biology
June 13, 2024

From academia to industry, at the intersection of computation, biology, and physics, Gevorg Grigoryan, PhD ’07, says there is no right path–just the path that works for you

A few years ago, Gevorg Grigoryan, PhD ‘07, then a professor at Dartmouth, had been pondering an idea for data-driven protein design for therapeutic applications. Unsure how to move forward with launching that concept into a company, he dug up an old syllabus from an entrepreneurship course he took during his PhD at MIT and decided to email the instructor for the class. 

He labored over the email for hours. It went from a few sentences to three pages, then back to a few sentences. Grigoryan finally hit send in the wee hours of the morning. 

Just 15 minutes later, he received a response from Noubar Afeyan, PhD ’87, the CEO and co-founder of venture capital company Flagship Pioneering (and the commencement speaker for the 2024 OneMIT Ceremony)

That ultimately led to Grigoryan, Afeyan, and others co-founding Generate:Biomedicines, where Grigoryan now serves as CTO.

“Success is defined by who is evaluating you,” Grigoryan says. “There is no right path—the best path for you is the one that works for you.” 

Generalizing Principles and Improving Lives

Generate:Biomedicines is the culmination of decades of advancements in machine learning, biological engineering, and medicine. Until recently, de novo design of a protein was extremely labor intensive, requiring months or years of computational methods and experiments. 

“Now, we can just push a button and have a generative model spit out a new protein with close to perfect probability it will actually work. It will fold. It will have the structure you’re intending,” Grigoryan says. “I think we’ve unearthed these generalizable principles for how to approach understanding complex systems, and I think it’s going to keep working.” 

Drug development was an obvious application for his work early on. Grigoryan says part of the reason he left academia—at least for now—are the resources available for this cutting-edge work.  

“Our space has a rather exciting and noble reason for existing,” he says. “We’re looking to improve human lives.”

Mixing Disciplines

Mixed-discipline STEM majors are increasingly common, but when Grigoryan was an undergraduate at the University of Maryland Baltimore County, little to no infrastructure existed for such an education.  

“There was this emerging intersection between physics, biology, and computational sciences,” Grigoryan recalls. “It wasn’t like there was this robust discipline at the intersection of those things—but I felt like there could be, and maybe I could be part of creating one.” 

He majored in Biochemistry and Computer Science, much to the confusion of his advisors for each major. This was so unprecedented that there wasn’t even guidance for which group he should walk with at graduation. 

Heading to Cambridge

Grigoryan admits his decision to attend MIT in the Department of Biology wasn’t systematic. 

“I was like ‘MIT sounds great, strong faculty, good techie school, good city. I’m sure I’ll figure something out,’” he says. “I can’t emphasize enough how important and formative those years at MIT were to who I ultimately became as a scientist.”

He worked with Amy Keating, then a junior faculty member, now Department Head for the Department of Biology, modeling protein-protein interactions. The work involved physics, math, chemistry, and biology. The Computational and Systems Biology PhD program was still a few years away, but the developing field was being recognized as important. 

Keating remains an advisor and confidant to this day. Grigoryan also commends her for her commitment to mentoring while balancing the demands of a faculty position—acquiring funding, running a research lab, and teaching. 

“It’s hard to make time to truly advise and help your students grow, but Amy is someone who took it very seriously and was very intentional about it,” Grigoryan says. “We spent a lot of time discussing ideas and doing science. The kind of impact that one can have through mentorship is hard to overestimate.”

Grigoryan next pursued a postdoc at UPenn with William “Bill” DeGrado, continuing to focus on protein design while gaining more experience in experimental approaches and exposure to thinking about proteins differently. 

Just by examining them, DeGrado had an intuitive understanding of molecules—anticipating their functionality or what mutations would disrupt that functionality. His predictive skill surpassed the abilities of computer modeling at the time. 

Grigoryan began to wonder: could computational models use prior observations to be at least as predictive as someone who spent a lot of time considering and observing the structure and function of those molecules?

Grigoryan next went to Dartmouth for a faculty position in computer science with cross-appointments in biology and chemistry to explore that question. 

Balancing Industry and Academia

Much of science is about trial and error, but early on, Grigoryan showed that accurate predictions of proteins and how they would bind, bond, and behave didn’t require starting from first principles. Models became more accurate by solving more structures and taking more binding measurements. 

Grigoryan credits the leaders at Flagship Pioneering for their initial confidence in the possible applications for this concept—more bullish, at the time, than Grigoryan himself. 

He spent four years splitting his time between Dartmouth and Cambridge and ultimately decided to leave academia altogether. 

“It was inevitable because I was just so in love with what we had built at Generate,” he says. “It was so exciting for me to see this idea come to fruition.” 

Pause or Grow

Grigoryan says the most important thing for a company is to scale at the right time, to balance “hitting the iron while it’s hot” while considering the readiness of the company, the technology, and the market. 

But even successful growth creates its own challenges. 

When there are fewer than two dozen people, aligning strategies across a company is straightforward: everyone can be in the room. However, growth—say, expanding to 200 employees—requires more deliberate communication and balancing agility while maintaining the company’s culture and identity.

“Growing is tough,” he says. “And it takes a lot of intentional effort, time, and energy to ensure a transparent culture that allows the team to thrive.” 

Grigoryan’s time in academia was invaluable for learning that “everything is about people”—but academia and industry require different mindsets. 

“Being a PI is about creating a lane for each of your trainees, where they’re essentially somewhat independent scientists,” he says. “In a company, by construction, you are bound by a set of common goals, and you have to value your work by the amount of synergy that it has with others, as opposed to what you can do only by yourself.” 

John Fucillo: Laying foundations for MIT’s Department of Biology

The Building 68 manager’s leadership, innovation, and laid-back attitude have helped to build a strong culture of community.

Samantha Edelen | Department of Biology
June 6, 2024

When you enter John Fucillo’s office at MIT, you will likely be greeted with an amiable nose boop and wagging tail from Shadow, a 4-year-old black lab, followed by a warm welcome from the office’s human occupant. Fucillo, manager of Building 68 — home to the MIT Department of Biology — is an animal lover, and Shadow is the gentlest of roughly nine dogs and one Siamese cat he’s taken care of throughout his life. Fortunately for the department, Shadow is not the only lab Fucillo cares for.

Fucillo came to MIT Biology in 1989 and says he couldn’t be happier. A Boston-area local, Fucillo previously spent two years working at Revere Beach, then learned skills as an auto mechanic, and later completed an apprenticeship with the International Brotherhood of Electrical Workers. As Building 68’s manager; environment, health, and safety coordinator; and chemical hygiene officer, Fucillo’s goal is to make workflows “easier, less expensive, more desirable, and more comfortable.” According to Mitchell Galanek, MIT radiation protection officer and Fucillo’s colleague for over 30 years, Fucillo was key for the department’s successful move into its new home when Building 68 was completed in 1994.

Throughout his time as a building manager, Fucillo has decreased routine spending and increased sustainability. He lowered the cost of lab coats by a whopping 92 percent — from $2,600 to $200 — with just one phone call to North Star, the building’s uniform/linens provider. Auditing the building’s plastic waste generation inspired the institute-wide MIT Lab Plastics Recycling Program, which now serves over 200 labs across campus. More than 50,000 pounds of plastic have been recycled in the last four years alone.

“John is not a cog in the wheel, but an integral part of the whole system,” says Anthony Fuccione, technical instructor and manager of the Biology Teaching lab.

Connecting and leading

Fucillo says one of his favorite parts of the job is chatting with researchers and helping them achieve their goals. He reportedly clocks about 10,000 steps per day on campus, responding to requests from labs, collaborating with colleagues, and connecting Biology to the Institute’s Environment, Health, and Safety (EHS) office.

“John is called upon — literally and figuratively — morning, noon, and night,” says Whitehead Professor of Molecular Genetics Monty Krieger. “He has had to become an expert in so very many areas to support staff, faculty, and students. His enormous success is due in part to his technical talents, in part to his genuine care for the welfare of his colleagues, and in part to his very special and caring personality.”

When MIT needed to comply with the Environmental Protection Agency’s decree to improve safety standards across campus, Fucillo sat on the committees tasked with meeting those standards while avoiding undue burden on researchers, establishing the Environmental Health and Safety Management system in 2002.

“From a safety perspective, that was one of the most challenging things MIT had to go through — but it came out at the end a better, safer, place,” says John Collins, EHS project technician and friend and colleague to Fucillo for over 20 years.

Fucillo later co-led the initiative for a 2011 overhaul of MIT’s management of regulated medical waste (RMW), such as Petri dishes, blood, and needles. Fucillo volunteered to pilot a new approach in Building 68 — despite a lukewarm response to the proposal from other biology EHS representatives, according to Galanek. This abundantly successful management system is now used by all MIT departments that generate RMW. It’s not only less expensive, but also does a better job at decontaminating waste than the previous management system.

“Anyone who has worked with John during his MIT career understands it is truly a privilege to partner with him,” Galanek says. “Not only does the work get done and done well, but you also gain a friend along the way.”

After consolidating a disparate group of individual lab assistants, Fucillo took on a supervisory role for the centralized staff tasked with cleaning glassware, preparing media, and ensuring consistency and sterility across Building 68 labs.

According to maintenance mechanic James (Jimmy) Carr, “you can’t find a better boss.”

“He’s just an easy-going guy,” says Karen O’Leary, who has worked with Fucillo for over 30 years. “My voice matters — I feel heard and respected by him.”

Looking forward

Although there are still many updates Fucillo hopes to see in Building 68, which will soon celebrate its 30th birthday, he is taking steps to cut back on his workload. He recently began passing on his knowledge to Facilities Manager and EHS Coordinator Cesar Duarte, who joined the department in 2023.

“It’s been a pleasure working alongside John and learning about the substantial role and responsibility he’s had in the biology department for the last three decades,” Duarte says. “Not only is John’s knowledge of Building 68 and the department’s history unparalleled, but his dedication to MIT and continued care and commitment to the health and well-being of the biology community throughout his career are truly remarkable.”

As he winds down his time at MIT, Fucillo hopes to spend more time on music, one of his earliest passions, which began when he picked up an accordion in first grade. He still plays guitar and bass nearly every day. When he rocks out at home more often, he’ll be leaving behind the foundations of innovation, leadership, and respect in Building 68.

The beauty of biology

Senior Hanjun Lee planned to pursue chemistry at MIT. A course in genetics changed that.

Lillian Eden | Department of Biology
May 16, 2024

When Hanjun Lee arrived at MIT, he was set on becoming a Course 5 chemistry student. Based on his experience in high school, biology was all about rote memorization.

That changed when he took course 7.03 (Genetics), taught by then-professor Aviv Regev, now head and executive vice president of research and early development at Genentech, and Peter Reddien, professor of biology and core member and associate director of the Whitehead Institute for Biomedical Research.

He notes that friends from other schools don’t cite a single course that changed their major, but he’s not alone in choosing Course 7 because of 7.03.

“Genetics has this interesting force, especially in MIT biology. The department’s historical — and active — role in genetics research ties directly into the way the course is taught,” Lee says. “Biology is about logic, scientific reasoning, and posing the right questions.”

A few years later, as a teaching assistant for class 7.002 (Fundamentals of Experimental Molecular Biology), he came to value how much care MIT biology professors take in presenting the material for all offered courses.

“I really appreciate how much effort MIT professors put into their teaching,” Lee says. “As a TA, you realize the beauty of how the professors organize these things — because they’re teaching you in a specific way, and you can grasp the beauty of it — there’s a beauty in studying and finding the patterns in nature.”

An undertaking to apply

To attend MIT at all hadn’t exactly been a lifelong dream. In fact, it didn’t occur to Lee that he could or should apply until he represented South Korea at the 49th International Chemistry Olympiad, where he won a Gold Medal in 2017. There, he had the chance to speak with MIT alumni, as well as current and aspiring students. More than half of those aspiring students eventually enrolled, Lee among them.

“Before that, MIT was this nearly mythical institution, so that experience really changed my life,” Lee recalls. “I heard so many different stories from people with so many different backgrounds — all converging towards the same enthusiasm towards science.”

At the time, Lee was already attending medical school — a six-year undergraduate program in Korea — that would lead to a stable career in medicine. Attending MIT would involve both changing his career plans and uprooting his life, leaving all his friends and family behind.

His parents weren’t especially enthusiastic about his desire to study at MIT, so it was up to Lee to meet the application requirements. He woke up at 3 a.m. to find his own way to the only SAT testing site in South Korea — an undertaking he now recalls with a laugh. In just three months, he had gathered everything he needed; MIT was the only institution in the United States Lee applied to.

He arrived in Cambridge, Massachusetts, in 2018 but attended MIT only for a semester before returning to Korea for his two years of mandatory military service.

“During military service, my goal was to read as many papers as possible, because I wondered what topic of science I’m drawn to — and many of the papers I was reading were authored by people I recognized, people who taught biology at MIT,” Lee says. “I became really interested in cancer biology.”

Return to MIT

When he returned to campus, Lee pledged to do everything he could to meet with faculty and discuss their work. To that end, he joined the MIT Undergraduate Research Journal, allowing him to interview professors. He notes that most MIT faculty are enthusiastic about being contacted by undergraduate students.

Stateside, Lee also reached out to Michael Lawrence, an assistant professor of pathology at Harvard Medical School and assistant geneticist at Mass General Cancer Center, about a preprint concerning APOBEC, an enzyme Lee had studied at Seoul National University. Lawrence’s lab was looking into APOBEC and cancer evolution — and the idea that the enzyme might drive drug resistance to cancer treatment.

“Since he joined my lab, I’ve been absolutely amazed by his scientific talents,” Lawrence says. “Hanjun’s scientific maturity and achievements are extremely rare, especially in an undergraduate student.”

Lee has made new discoveries from genomic data and was involved in publishing a paper in Molecular Cell and a paper in Nature Genetics. In the latter, the lab identified the source of background noise in chromosome conformation capture experiments, a technique for analyzing chromatin in cells.

Lawrence thinks Lee “is destined for great leadership in science.” In the meantime, Lee has gained valuable insights into how much work these types of achievements require.

“Doing research has been rewarding, but it also taught me to appreciate that science is almost 100 percent about failures,” Lee says. “It is those failures that end up leading you to the path of success.”

Widening the scope

Lee’s personal motto is that to excel in a specific field, one must have a broad sense of what the entire field looks like, and suggests other budding scientists enroll in courses distant from their research area. He also says it was key to see his peers as collaborators rather than competitors, and that each student will excel in their own unique way.

“Your MIT experience is defined by interactions with others,” Lee says. “They will help identify and shape your path.”

For his accomplishments, Lee was recently named an American Association for Cancer Research Undergraduate Scholar. Last year, he also spoke at the Gordon Research Conference on Cell Growth and Proliferation about his work on the retinoblastoma gene product RB.

Encouraged by positive course evaluations during his time as a TA, Lee hopes to inspire other students in the future through teaching. Lee has recently decided to pursue a PhD in cancer biology at Harvard Medical School, although his interests remain broad.

“I want to explore other fields of biology as well,” he says. “I have so many questions that I want to answer.”

Although initially resistant, Lee’s mother and father are now “immensely proud to be MIT parents” and will be coming to Cambridge in May to celebrate Lee’s graduation.

“Throughout my years here, they’ve been able to see how I’ve changed,” he says. “I don’t think I’m a great scientist, yet, but I now have some sense of how to become one.”

A day in the life of graduate student and plant scientist Carly Martin

Carly Martin is developing a detailed map showcasing which genes are turned on or off across cell types during seed development as a graduate student in the Gehring Lab. In a new video series from the Whitehead Institute, see what a typical day is like for her as she explores innovative ways to enhance agricultural sustainability.

Shafaq Zia | Whitehead Institute
May 14, 2024
Staff Spotlight: John Fucillo, Building 68 Manager, EHS Coordinator; Chemical Hygiene Officer

Laying foundations for MIT Biology

Samantha Edelen | Department of Biology
May 2, 2024

Building 68 manager John Fucillo’s leadership, innovation, and laid-back attitude have built a community culture that will never be taken for granted. 

When entering the office of Building 68’s manager, you will likely be greeted first with an amiable nose boop and wagging tail from Shadow, a four-year-old black lab, followed by a warm welcome from the office’s other occupant, John Fucillo. Fucillo is an animal lover, and Shadow is the gentlest of roughly nine dogs and one Siamese cat he’s taken care of throughout his life. Fortunately for MIT Biology, Shadow is not the only lab Fucillo cares for. 

A Boston area local, Fucillo spent two years working at Revere Beach, then learned skills as an auto mechanic, and later completed an apprenticeship with the International Brotherhood of Electrical Workers. In 1989, Fucillo came to MIT Biology and says he couldn’t be happier.

As Building 68’s manager, Environment, Health & Safety coordinator, and Chemical Hygiene Officer, Fucillo’s goal is to make workflows “easier, less expensive, more desirable, and more comfortable.”

Fucillo was key for the Department’s successful move into its new home when Building 68 was completed in 1994, according to Mitchell Galanek, MIT Radiation Protection Officer and Fucillo’s colleague for over 30 years. 

Throughout his time as a building manager, Fucillo has decreased routine spending and increased sustainability. He lowered the cost of lab coats by a whopping 92%–from $2,600 to $200–with just one phone call to North Star, the building’s uniform/linens provider. Auditing the building’s plastic waste generation inspired the institute-wide MIT Lab Plastics Recycling Program, which now serves over 200 labs across campus. More than 50,000 lbs of plastic have been recycled in the last four years alone. 

“John is not a cog in the wheel, but an integral part of the whole system,” says Anthony Fuccione, Technical Instructor and Manager of the Biology Teaching lab.

Connecting and leading 

Fucillo says one of his favorite parts of the job is chatting with researchers and helping them achieve their goals. He reportedly clocks about 10,000 steps per day on campus, responding to requests from labs, collaborating with colleagues, and connecting Biology to the institute’s Environment, Health, & Safety office.

“John is called upon — literally and figuratively — morning, noon, and night,” says Whitehead Professor of Molecular Genetics Monty Krieger. “He has had to become an expert in so very many areas to support staff, faculty, and students. His enormous success is due in part to his technical talents, in part to his genuine care for the welfare of his colleagues, and in part to his very special and caring personality.” 

When MIT needed to comply with the EPA’s decree to improve safety standards across campus, Fucillo sat on the committees tasked with meeting those standards while avoiding undue burden on researchers, establishing the Environmental Health and Safety Management system in 2002.

“From a safety perspective, that was one of the most challenging things MIT had to go through–but it came out at the end a better, safer, place,” says John Collins, EHS Project Technician and friend and colleague to Fucillo for over 20 years.

Fucillo later co-led the initiative for a 2011 overhaul of MIT’s management of regulated medical waste (RMW), such as Petri dishes, blood, and needles. Fucillo volunteered to pilot a new approach in Building 68 — despite a lukewarm response to the proposal from other Biology EHS representatives, according to Galanek. This abundantly successful management system is now used by all MIT departments that generate RMW. It’s not only less expensive, but also does a better job at decontaminating waste than the previous management system.

“Anyone who has worked with John during his MIT career understands it is truly a privilege to partner with him,” Galanek says. “Not only does the work get done and done well, but you also gain a friend along the way.”

After consolidating a disparate group of individual lab assistants, Fucillo took on a supervisory role for the centralized staff tasked with cleaning glassware, preparing media, and ensuring consistency and sterility across Building 68 labs. 

According to maintenance mechanic James “Jimmy” Carr, “you can’t find a better boss.”

“He’s just an easy-going guy,” says Karen O’Leary, who has worked with Fucillo for over 30 years. “My voice matters–I feel heard and respected by him.” 

Looking forward

Although there are still many updates Fucillo hopes to see in Building 68, which will soon celebrate its 30th birthday, he is taking steps to cut back on his workload. 

He recently began passing on his knowledge to Facilities Manager and EHS Coordinator Cesar Duarte, who joined the department in 2023.

“It’s been a pleasure working alongside John and learning about the substantial role and responsibility he’s had in the Biology department for the last three decades,” Duarte says. “Not only is John’s knowledge of Building 68 and the department’s history unparalleled, but his dedication to MIT and continued care and commitment to the health and well-being of the Biology community throughout his career are truly remarkable.”

As he winds down his time at MIT, Fucillo hopes to spend more time on music, one of his earliest passions, which began when he picked up an accordion in first grade. He still plays guitar and bass nearly every day. When he rocks out at home more often, he’ll be leaving behind the foundations of innovation, leadership, and respect in Building 68.

Student spotlight: Victory Yinka-Banjo (6-7)

The junior, who is majoring in computer science and molecular biology, wants to “make it a norm to lift others as I continue to climb.”

March 27, 2024
What can super-healing species teach us about regeneration?

Albert Almada PhD ’13 studies the mechanics of how stem cells rebuild tissues. “Digging deep into the science is what MIT taught me,” he says.

Lillian Eden | Department of Biology
February 21, 2024

When Albert E. Almada PhD ’13 embarks on a new project, he always considers two criteria instilled in him during his time as a graduate student in the Department of Biology at MIT.

“If you want to make a big discovery, you have to approach it from a unique perspective — a unique angle,” Almada says. “You also have to be willing to dive into the unknown and go to the leading edge of your field.”

This is not without its challenges — but with an innovative spirit, Almada says, one can find ways to apply technologies and approaches to a new area of research where a roadmap doesn’t yet exist.

Now an assistant professor of orthopedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of the University of Southern California (USC), Almada studies the mechanics of how stem cells rebuild tissues after trauma and how stem cell principles are dysregulated and drive conditions like degenerative disease and aging, exploring these topics through an evolutionary lens.

He’s also trying to solve a mystery that has intrigued scientists for centuries: Why can some vertebrate species like fish, salamanders, and lizards regenerate entire body parts, but mammals cannot? Almada’s laboratory at USC tackles these critical questions in the musculoskeletal system.

Almada’s fascination with muscle development and regeneration can be traced back to growing up in southern California. Almada’s brother had a degenerative muscle disease called Duchenne muscular dystrophy — and, while Almada grew stronger and stronger, his brother grew weaker and weaker. Last summer, Almada’s brother, unfortunately, lost his battle with his disorder at the age of 41.

“Watching his disease progress in those early years is what inspired me to become a scientist,” Almada recalls. “Sometimes science can be personal.”

Almada went to the University of California at Irvine for his undergraduate degree, majoring in biological sciences. During his summers, he participated in the Undergraduate Research Program (URP) at the Cold Spring Harbor Laboratory and the MIT Summer Research Program-Bio (now the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, BSG-MSRP-Bio), where he saw the passion, rigor, and drive that solidified his desire to pursue a PhD.

Despite his interest in clinical applications, skeletal muscle, and regenerative biology, Almada was drawn to the Department of Biology at MIT, which is focused on basic fundamental research.

“I was willing to bet that it all came down to understanding basic cellular processes and things going wrong with the cell and how it interacts with its environment,” he says. “The MIT biology program really helped me define an identity for myself and gave me a template for how to tackle clinical problems from a molecular perspective.”

Almada’s PhD thesis work was based on a curious finding that Phillip Sharp, Institute Professor emeritus, professor emeritus of biology, and intramural faculty at the Koch Institute for Integrative Cancer Research, had made in 2007 — that transcription, the process of copying DNA into a messenger molecule called RNA, can occur in both directions at gene promoters. In one direction, it was long understood that fully formed mRNA is transcribed and can be used as a blueprint to make a protein. The transcription Sharp observed, in the opposite direction, results in a very short RNA that is not used as a gene product blueprint.

Almada’s project dug into what those short RNA molecules are — their structure and sequence, and why they’re not produced the same way that coding messenger RNA is. In two papers published in PNAS and Nature, Almada and colleagues discovered that a balance between splicing and transcription termination signals controls the length of an RNA. This finding has wider implications because toxic RNAs are produced and can build up in several degenerative diseases; being able to splice out or shorten RNAs to remove the harmful segments could be a potential therapeutic treatment.

“That experience convinced me that if I want to make big discoveries, I have to focus on basic science,” he says. “It also gave me the confidence that if I can succeed at MIT, I can succeed just about anywhere and in any field of biology.”

At the time Almada was in graduate school, there was a lot of excitement about transcription factor reprogramming. Transcription factors are the proteins responsible for turning on essential genes that tell a cell what to be and how to behave; a subset of them can even theoretically turn one cell type into another.

Almada began to wonder whether a specialized set of transcription factors instructs stem cells to rebuild tissues after trauma. After MIT, Almada moved on to a postdoctoral position in the lab of Amy Wagers, a leader in muscle stem cell biology at Harvard University, to immerse himself in this problem.

In many tissues in our bodies, a population of stem cells typically exists in an inactive, non-dividing state called quiescence. Once activated, these stem cells interact with their environment, sense damage signals, and turn on programs of proliferation and differentiation, as well as self-renewal, which is critical to maintaining a pool of stem cells in the tissue.

One of the biggest mysteries in the field of regenerative biology is how stem cells transition from dormancy into that activated, highly regenerative state. The body’s ability to turn on stem cells, including those in the skeletal muscle system, declines as we age and is often dysregulated in degenerative diseases — diseases like the one Almada’s brother suffered from.

In a study Almada published in Cell Reports several years ago, he identified a family of transcription factors that work together to turn on a critical regenerative gene program within hours of muscle trauma. This program drives muscle stem cells out of quiescence and speeds up healing.

“Now my lab is studying this regenerative program and its potential dysregulation in aging and degenerative muscle diseases using mouse and human models,” Almada says. “We’re also drawing parallels with super-healing species like salamanders and lizards.”

Recently, Almada has been working on characterizing the molecular and functional properties of stem cells in lizards, attempting to understand how the genes and pathways differ from mammalian stem cells. Lizards can regenerate massive amounts of skeletal muscle from scratch — imagine if human muscle tissue could be regrown as seamlessly as a lizard’s tail can. He is also exploring whether the tail is unique, or if stem cells in other tissues in lizards can regenerate faster and better than the tail, by comparing analogous injuries in a mouse model.

“This is a good example of approaching a problem from a new perspective: We believe we’re going to discover new biology in lizards that we can use to enhance skeletal muscle growth in vulnerable human populations, including those that suffer from deadly muscle disorders,” Almada says.

In just three years of starting his faculty position at USC, his work and approach have already received recognition in academia, with junior faculty awards from the Baxter Foundation and the Glenn Foundation/American Federation of Aging Research. He also received his first RO1 award from the National Institutes of Health with nearly $3 million in funding. Almada and his first graduate student, Alma Zuniga Munoz, were also awarded the HHMI Gilliam Fellowship last summer. Zuniga Munoz is the first to be recognized with this award at USC; fellowship recipients, student and advisor pairs, are selected with the goal of preparing students from underrepresented groups for leadership roles in science.

Almada himself is a second-generation Mexican American and has been involved in mentoring and training throughout his academic career. He was a graduate resident tutor for Spanish House at MIT and currently serves as the chair of the Diversity, Equity, and Inclusion Committee in the Department of Stem Cell Biology and Regenerative Medicine at USC; more than half of his lab members identify as members of the Hispanic community.

“The focus has to be on developing good scientists,” Almada says. “I learned from my past research mentors the importance of putting the needs of your students first and providing a supportive environment for everyone to excel, no matter where they start.”

As a mentor and researcher, Almada knows that no question and no challenge is off limits — foundations he built in Cambridge, where his graduate studies focused on teaching him to think, not just do.

“Digging deep into the science is what MIT taught me,” he says. “I’m now taking all of my knowledge in molecular biology and applying it to translationally oriented questions that I hope will benefit human health and longevity.”