Placement: Promote to Homepage
Second annual assembly, sponsored by the Department of Biology and Picower Institute, invited postdocs from across the country to meet with faculty, present their work to the MIT community, and build relationships.
Lillian Eden | Department of Biology
June 10, 2024
For science — and the scientists who practice it — to succeed, research must be shared. That’s why members of the MIT community recently gathered to learn about the research of eight postdocs from across the country for the second annual Catalyst Symposium, an event co-sponsored by the Department of Biology and The Picower Institute for Learning and Memory.
The eight Catalyst Fellows came to campus as part of an effort to increase engagement between MIT scholars and postdocs excelling in their respective fields from traditionally underrepresented backgrounds in science. The three-day symposium included panel discussions with faculty and postdocs, one-on-one meetings, social events, and research talks from the Catalyst Fellows.
“I love the name of this symposium because we’re all, of course, eager to catalyze advancements in our professional lives, in science, and to move forward faster by lowering activation barriers,” says MIT biology department head Amy Keating. “I feel we can’t afford to do science with only part of the talent pool, and I don’t think people can do their best work when they are worried about whether they belong.”
The 2024 Catalyst Fellows include Chloé Baron from Boston Children’s Hospital; Maria Cecília Canesso from The Rockefeller University; Kiara Eldred from the University of Washington School of Medicine; Caitlin Kowalski from the University of Oregon; Fabián Morales-Polanco from Stanford University; Kali Pruss from the Washington University School of Medicine in St. Louis; Rodrigo Romero from Memorial Sloan Kettering Cancer Center; and Zuri Sullivan from Harvard University.
Romero, who received his PhD from MIT working in the Jacks Lab at the Koch Institute, said that it was “incredible to see so many familiar faces,” but he spent the symposium lunch chatting with new students in his old lab.
“Especially having been trained to think differently after MIT, I can now reach out to people that I didn’t as a graduate student, and make connections that I didn’t think about before,” Romero says.
He presented his work on lineage plasticity in the tumor microenvironment. Lineage plasticity is a hallmark of tumor progression but also occurs during normal development, such as wound healing.
As for the general mission of the symposium, Romero agrees with Keating.
“Trying to lower the boundary for other people to actually have a chance to do academic research in the future is important,” Romero says.
The Catalyst Symposium is aimed at early-career scientists who foresee a path in academia. Of the 2023 Catalyst Fellows, one has already secured a faculty position. Starting this September, Shan Maltzer will be an assistant professor at Vanderbilt University in the Department of Pharmacology and the Vanderbilt Brain Institute studying mechanisms of somatosensory circuit assembly, development, and function.
Another aim of the Catalyst Symposium is to facilitate collaborations and strengthen existing relationships. Sullivan, an immunologist and molecular neuroscientist who presented on the interactions between the immune system and the brain, is collaborating with Sebastian Lourido, an associate professor of biology and core member of the Whitehead Institute for Biomedical Research. Lourido’s studies include pathogens such as Toxoplasma gondii, which is known to alter the behavior of infected rodents. In the long term, Sullivan hopes to bridge research in immunology and neuroscience — for instance by investigating how infection affects behavior. She has observed that two rodents experiencing illness will huddle together in a cage, whereas an unafflicted rodent and an ill one will generally avoid each other when sharing the same space.
Pruss presented research on the interactions between the gut microbiome and the environment, and how they may affect physiology and fetal development. Kowalski discussed the relationship between fungi residing on our bodies and human health. Beyond the opportunity to deliver talks, both agreed that the small group settings of the three-day event were rewarding.
“The opportunity to meet with faculty throughout the symposium has been invaluable, both for finding familiar faces and for establishing friendly relationships,” Pruss says. “You don’t have to try to catch them when you’re running past them in the hallway.”
Eldred, who studies cell fate in the human retina, says she was excited about the faculty panels because they allowed her to ask faculty about fundamental aspects of recruiting for their labs, like bringing in graduate students.
Kowalski also says she enjoyed interfacing with so many new ideas — the spread of scientific topics from among the cohort of speakers extended beyond those she usually interacts with.
Mike Laub, professor of biology and Howard Hughes Medical Institute investigator, and Yadira Soto-Feliciano, assistant professor of biology and intramural faculty at the Koch Institute for Integrative Cancer Research, were on the symposium’s planning committee, along with Diversity, Equity, and Inclusion Officer Hallie Dowling-Huppert. Laub hopes the symposium will continue to be offered annually; next year’s Catalyst Symposium is already scheduled to take place in early May.
“I thought this year’s Catalyst Symposium was another great success. The talks from the visiting fellows featured some amazing science from a wide range of fields,” Laub says. “I also think it’s fair to say that their interactions with the faculty, postdocs, and students here generated a lot of excitement and energy in our community, which is exactly what we hoped to accomplish with this symposium.”
New camera chip design allows for optimizing each pixel’s timing to maximize signal to noise ratio when tracking real-time visual indicator of neural voltage, described in a new paper from a team in the Wilson Lab published in Nature Communications.
David Orenstein | The Picower Institute for Learning and Memory
June 7, 2024
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.
By capturing short-lived RNA molecules, scientists can map relationships between genes and the regulatory elements that control them.
Anne Trafton | MIT News
June 5, 2024
The human genome contains about 23,000 genes, but only a fraction of those genes are turned on inside a cell at any given time. The complex network of regulatory elements that controls gene expression includes regions of the genome called enhancers, which are often located far from the genes that they regulate.
This distance can make it difficult to map the complex interactions between genes and enhancers. To overcome that, MIT researchers have invented a new technique that allows them to observe the timing of gene and enhancer activation in a cell. When a gene is turned on around the same time as a particular enhancer, it strongly suggests the enhancer is controlling that gene.
Learning more about which enhancers control which genes, in different types of cells, could help researchers identify potential drug targets for genetic disorders. Genomic studies have identified mutations in many non-protein-coding regions that are linked to a variety of diseases. Could these be unknown enhancers?
“When people start using genetic technology to identify regions of chromosomes that have disease information, most of those sites don’t correspond to genes. We suspect they correspond to these enhancers, which can be quite distant from a promoter, so it’s very important to be able to identify these enhancers,” says Phillip Sharp, an MIT Institute Professor Emeritus and member of MIT’s Koch Institute for Integrative Cancer Research.
Sharp is the senior author of the new study, which appears today in Nature. MIT Research Assistant D.B. Jay Mahat is the lead author of the paper.
Hunting for eRNA
Less than 2 percent of the human genome consists of protein-coding genes. The rest of the genome includes many elements that control when and how those genes are expressed. Enhancers, which are thought to turn genes on by coming into physical contact with gene promoter regions through transiently forming a complex, were discovered about 45 years ago.
More recently, in 2010, researchers discovered that these enhancers are transcribed into RNA molecules, known as enhancer RNA or eRNA. Scientists suspect that this transcription occurs when the enhancers are actively interacting with their target genes. This raised the possibility that measuring eRNA transcription levels could help researchers determine when an enhancer is active, as well as which genes it’s targeting.
“That information is extraordinarily important in understanding how development occurs, and in understanding how cancers change their regulatory programs and activate processes that lead to de-differentiation and metastatic growth,” Mahat says.
However, this kind of mapping has proven difficult to perform because eRNA is produced in very small quantities and does not last long in the cell. Additionally, eRNA lacks a modification known as a poly-A tail, which is the “hook” that most techniques use to pull RNA out of a cell.
One way to capture eRNA is to add a nucleotide to cells that halts transcription when incorporated into RNA. These nucleotides also contain a tag called biotin that can be used to fish the RNA out of a cell. However, this current technique only works on large pools of cells and doesn’t give information about individual cells.
While brainstorming ideas for new ways to capture eRNA, Mahat and Sharp considered using click chemistry, a technique that can be used to join two molecules together if they are each tagged with “click handles” that can react together.
The researchers designed nucleotides labeled with one click handle, and once these nucleotides are incorporated into growing eRNA strands, the strands can be fished out with a tag containing the complementary handle. This allowed the researchers to capture eRNA and then purify, amplify, and sequence it. Some RNA is lost at each step, but Mahat estimates that they can successfully pull out about 10 percent of the eRNA from a given cell.
Using this technique, the researchers obtained a snapshot of the enhancers and genes that are being actively transcribed at a given time in a cell.
“You want to be able to determine, in every cell, the activation of transcription from regulatory elements and from their corresponding gene. And this has to be done in a single cell because that’s where you can detect synchrony or asynchrony between regulatory elements and genes,” Mahat says.
Timing of gene expression
Demonstrating their technique in mouse embryonic stem cells, the researchers found that they could calculate approximately when a particular region starts to be transcribed, based on the length of the RNA strand and the speed of the polymerase (the enzyme responsible for transcription) — that is, how far the polymerase transcribes per second. This allowed them to determine which genes and enhancers were being transcribed around the same time.
The researchers used this approach to determine the timing of the expression of cell cycle genes in more detail than has previously been possible. They were also able to confirm several sets of known gene-enhancer pairs and generated a list of about 50,000 possible enhancer-gene pairs that they can now try to verify.
Learning which enhancers control which genes would prove valuable in developing new treatments for diseases with a genetic basis. Last year, the U.S. Food and Drug Administration approved the first gene therapy treatment for sickle cell anemia, which works by interfering with an enhancer that results in activation of a fetal globin gene, reducing the production of sickled blood cells.
The MIT team is now applying this approach to other types of cells, with a focus on autoimmune diseases. Working with researchers at Boston Children’s Hospital, they are exploring immune cell mutations that have been linked to lupus, many of which are found in non-coding regions of the genome.
“It’s not clear which genes are affected by these mutations, so we are beginning to tease apart the genes these putative enhancers might be regulating, and in what cell types these enhancers are active,” Mahat says. “This is a tool for creating gene-to-enhancer maps, which are fundamental in understanding the biology, and also a foundation for understanding disease.”
The findings of this study also offer evidence for a theory that Sharp has recently developed, along with MIT professors Richard Young and Arup Chakraborty, that gene transcription is controlled by membraneless droplets known as condensates. These condensates are made of large clusters of enzymes and RNA, which Sharp suggests may include eRNA produced at enhancer sites.
“We picture that the communication between an enhancer and a promoter is a condensate-type, transient structure, and RNA is part of that. This is an important piece of work in building the understanding of how RNAs from enhancers could be active,” he says.
The research was funded by the National Cancer Institute, the National Institutes of Health, and the Emerald Foundation Postdoctoral Transition Award.
To study plasticity in the brain, neuroscientists seek to track it at high resolution across whole cells, which is challenging in part because brain tissue is notorious for scattering light and making images fuzzy. A newly described technology described in a paper in Scientific Reports improves the clarity and speed of using two-photon microscopy to image synapses in the live brain. The paper was co-authored by Elly Nedivi, the William R. (1964) and Linda R. Young Professor of Neuroscience in the Picower Institute for Learning and Memory and the Department of Biology.
David Orenstein | The Picower Institute for Learning and Memory
June 4, 2024
An atlas of human protein kinases enables scientists to map cell signaling pathways with unprecedented speed and detail. Michael Yaffe, the David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the new study published in Nature, is hoping to apply the comprehensive atlas of enzymes that regulate a wide variety of cellular activities to individual patients’ tumors to learn more about how the signaling states differ in cancer cancer, which could reveal new
Megan Scudellari | Koch Institute
June 3, 2024
A newly complete database of human protein kinases and their preferred binding sites provides a powerful new platform to investigate cell signaling pathways.
Culminating 25 years of research, MIT, Harvard University, and Yale University scientists and collaborators have unveiled a comprehensive atlas of human tyrosine kinases — enzymes that regulate a wide variety of cellular activities — and their binding sites.
The addition of tyrosine kinases to a previously published dataset from the same group now completes a free, publicly available atlas of all human kinases and their specific binding sites on proteins, which together orchestrate fundamental cell processes such as growth, cell division, and metabolism.
Now, researchers can use data from mass spectrometry, a common laboratory technique, to identify the kinases involved in normal and dysregulated cell signaling in human tissue, such as during inflammation or cancer progression.
“I am most excited about being able to apply this to individual patients’ tumors and learn about the signaling states of cancer and heterogeneity of that signaling,” says Michael Yaffe, who is the David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the new study. “This could reveal new druggable targets or novel combination therapies.”
The study, published in Nature, is the product of a long-standing collaboration with senior authors Lewis Cantley at Harvard Medical School and Dana-Farber Cancer Institute, Benjamin Turk at Yale School of Medicine, and Jared Johnson at Weill Cornell Medical College.
The paper’s lead authors are Tomer Yaron-Barir at Columbia University Irving Medical Center, and MIT’s Brian Joughin, with contributions from Kontstantin Krismer, Mina Takegami, and Pau Creixell.
Kinase kingdom
Human cells are governed by a network of diverse protein kinases that alter the properties of other proteins by adding or removing chemical compounds called phosphate groups. Phosphate groups are small but powerful: When attached to proteins, they can turn proteins on or off, or even dramatically change their function. Identifying which of the almost 400 human kinases phosphorylate a specific protein at a particular site on the protein was traditionally a lengthy, laborious process.
Beginning in the mid 1990s, the Cantley laboratory developed a method using a library of small peptides to identify the optimal amino acid sequence — called a motif, similar to a scannable barcode — that a kinase targets on its substrate proteins for the addition of a phosphate group. Over the ensuing years, Yaffe, Turk, and Johnson, all of whom spent time as postdocs in the Cantley lab, made seminal advancements in the technique, increasing its throughput, accuracy, and utility.
Johnson led a massive experimental effort exposing batches of kinases to these peptide libraries and observed which kinases phosphorylated which subsets of peptides. In a corresponding Nature paper published in January 2023, the team mapped more than 300 serine/threonine kinases, the other main type of protein kinase, to their motifs. In the current paper, they complete the human “kinome” by successfully mapping 93 tyrosine kinases to their corresponding motifs.
Next, by creating and using advanced computational tools, Yaron-Barir, Krismer, Joughin, Takegami, and Yaffe tested whether the results were predictive of real proteins, and whether the results might reveal unknown signaling events in normal and cancer cells. By analyzing phosphoproteomic data from mass spectrometry to reveal phosphorylation patterns in cells, their atlas accurately predicted tyrosine kinase activity in previously studied cell signaling pathways.
For example, using recently published phosphoproteomic data of human lung cancer cells treated with two targeted drugs, the atlas identified that treatment with erlotinib, a known inhibitor of the protein EGFR, downregulated sites matching a motif for EGFR. Treatment with afatinib, a known HER2 inhibitor, downregulated sites matching the HER2 motif. Unexpectedly, afatinib treatment also upregulated the motif for the tyrosine kinase MET, a finding that helps explain patient data linking MET activity to afatinib drug resistance.
Actionable results
There are two key ways researchers can use the new atlas. First, for a protein of interest that is being phosphorylated, the atlas can be used to narrow down hundreds of kinases to a short list of candidates likely to be involved. “The predictions that come from using this will still need to be validated experimentally, but it’s a huge step forward in making clear predictions that can be tested,” says Yaffe.
Second, the atlas makes phosphoproteomic data more useful and actionable. In the past, researchers might gather phosphoproteomic data from a tissue sample, but it was difficult to know what that data was saying or how to best use it to guide next steps in research. Now, that data can be used to predict which kinases are upregulated or downregulated and therefore which cellular signaling pathways are active or not.
“We now have a new tool now to interpret those large datasets, a Rosetta Stone for phosphoproteomics,” says Yaffe. “It is going to be particularly helpful for turning this type of disease data into actionable items.”
In the context of cancer, phosophoproteomic data from a patient’s tumor biopsy could be used to help doctors quickly identify which kinases and cell signaling pathways are involved in cancer expansion or drug resistance, then use that knowledge to target those pathways with appropriate drug therapy or combination therapy.
Yaffe’s lab and their colleagues at the National Institutes of Health are now using the atlas to seek out new insights into difficult cancers, including appendiceal cancer and neuroendocrine tumors. While many cancers have been shown to have a strong genetic component, such as the genes BRCA1 and BRCA2 in breast cancer, other cancers are not associated with any known genetic cause. “We’re using this atlas to interrogate these tumors that don’t seem to have a clear genetic driver to see if we can identify kinases that are driving cancer progression,” he says.
Biological insights
In addition to completing the human kinase atlas, the team made two biological discoveries in their recent study. First, they identified three main classes of phosphorylation motifs, or barcodes, for tyrosine kinases. The first class is motifs that map to multiple kinases, suggesting that numerous signaling pathways converge to phosphorylate a protein boasting that motif. The second class is motifs with a one-to-one match between motif and kinase, in which only a specific kinase will activate a protein with that motif. This came as a partial surprise, as tyrosine kinases have been thought to have minimal specificity by some in the field.
The final class includes motifs for which there is no clear match to one of the 78 classical tyrosine kinases. This class includes motifs that match to 15 atypical tyrosine kinases known to also phosphorylate serine or threonine residues. “This means that there’s a subset of kinases that we didn’t recognize that are actually playing an important role,” says Yaffe. It also indicates there may be other mechanisms besides motifs alone that affect how a kinase interacts with a protein.
The team also discovered that tyrosine kinase motifs are tightly conserved between humans and the worm species C. elegans, despite the species being separated by more than 600 million years of evolution. In other words, a worm kinase and its human homologue are phosphorylating essentially the same motif. That sequence preservation suggests that tyrosine kinases are highly critical to signaling pathways in all multicellular organisms, and any small change would be harmful to an organism.
The research was funded by the Charles and Marjorie Holloway Foundation, the MIT Center for Precision Cancer Medicine, the Koch Institute Frontier Research Program via L. Scott Ritterbush, the Leukemia and Lymphoma Society, the National Institutes of Health, Cancer Research UK, the Brain Tumour Charity, and the Koch Institute Support (core) grant from the National Cancer Institute.
Whitehead Institute Director and President Ruth Lehmann has been named a Foreign Member of the Royal Society. The election recognizes her “pioneering studies of the mechanisms underlying the embryonic development and reproduction of the fruit fly Drosophila.” It honors her work establishing the role of messenger RNA localization in specifying the antero-posterior body axis and germ line development and additionally notes her discoveries that revealed the role of lipid-based signaling pathways in the migration of germ cells to the developing gonads.
Lisa Girard | Whitehead Institute
May 22, 2024
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.”
Lowering ‘activation barriers’ for rising biology researchers
Lillian Eden | Department of Biology
May 16, 2024
The second annual Catalyst Symposium, sponsored by the Department of Biology and Picower Institute for Learning and Memory, invited postdocs from across the country to meet with faculty, present their work to the MIT community, and build relationships.
For science — and the scientists who practice it — to succeed, it must be shared. That’s why members of the MIT community recently gathered to learn about the research of eight postdocs from across the country for the second annual Catalyst Symposium, an event co-sponsored by the Department of Biology and The Picower Institute for Learning and Memory.
The eight Catalyst Fellows came to campus as part of an effort to increase engagement between MIT scholars and postdocs excelling in their respective fields from traditionally underrepresented backgrounds in science. The three-day symposium included panel discussions with faculty and postdocs, one-on-one meetings, social events, and research talks from the Catalyst Fellows.
“I love the name of this symposium because we’re all, of course, eager to catalyze advancements in our professional lives, in science, and to move forward faster by lowering activation barriers,” says MIT Biology Department Head Amy Keating. “I feel we can’t afford to do science with only part of the talent pool, and I don’t think people can do their best work when they are worried about whether they belong.”
The cohort of 2024 Catalyst Fellows included: Chloé Baron from Boston Children’s Hospital; Maria Cecília Canesso from The Rockefeller University; Kiara Eldred from the University of Washington School of Medicine; Caitlin Kowalski from the University of Oregon; Fabián Morales-Polanco from Stanford University; Kali Pruss from the Washington University School of Medicine in St. Louis; Rodrigo Romero from Memorial Sloan Kettering Cancer Center; and Zuri Sullivan from Harvard University.
Romero, who received his PhD from MIT working in the Jacks Lab at the Koch Institute, said that it was “incredible to see so many familiar faces,” but he spent the Symposium lunch chatting with new students in his old lab.
“Especially having been trained to think differently after MIT, I can now reach out to people that I didn’t as a graduate student, and make connections that I didn’t think about before,” Romero says.
He presented his work on lineage plasticity in the tumor microenvironment. Lineage plasticity is a hallmark of tumor progression but also occurs during normal development, such as wound healing.
As for the general mission of the symposium, Romero agreed with Keating.
“Trying to lower the boundary for other people to actually have a chance to do academic research in the future is important,” Romero says.
The Catalyst Symposium is aimed at early-career scientists who foresee a path in academia. Of the 2023 Catalyst Fellows, one has already secured a faculty position. Starting in September 2024, Shan Maltzer will be an assistant professor at Vanderbilt University in the Department of Pharmacology and the Vanderbilt Brain Institute studying mechanisms of somatosensory circuit assembly, development, and function.
Another aim of the Catalyst Symposium is to facilitate collaborations and strengthen existing relationships. Sullivan, an immunologist and molecular neuroscientist who presented on the interactions between the immune system and the brain, is collaborating with Sebastian Lourido, an Associate Professor of Biology and Core Member of the Whitehead Institute. Lourido’s studies include pathogens such as Toxoplasma gondii, which is known to alter the behavior of infected rodents. In the long term, Sullivan hopes to bridge research in immunology and neuroscience — for instance by investigating how infection affects behavior. She has observed that two rodents experiencing illness will huddle together in a cage, whereas an unafflicted rodent and an ill one will generally avoid each other when sharing the same space.
Pruss presented research on the interactions between the gut microbiome and the environment, and how they may affect physiology and fetal development. Kowalski discussed the relationship between fungi residing on our bodies and human health. Beyond the opportunity to deliver talks, both agreed that the small group settings of the three-day event were rewarding.
“The opportunity to meet with faculty throughout the symposium has been invaluable, both for finding familiar faces and for establishing friendly relationships,” Pruss says. “You don’t have to try to catch them when you’re running past them in the hallway.”
Eldred, who studies cell fate in the human retina, says she was excited about the faculty panels because they allowed her to ask faculty about fundamental aspects of recruiting for their labs, like bringing in graduate students.
Kowalski also says she enjoyed interfacing with so many new ideas — the spread of scientific topics from among the cohort of speakers extended beyond those she usually interacts with.
Mike Laub, Professor of Biology and HHMI Investigator, and Yadira Soto-Feliciano, Assistant Professor of Biology and Intramural Faculty at the Koch Institute, were on the symposium’s planning committee, along with Diversity, Equity, and Inclusion Officer Hallie Dowling-Huppert. Laub hopes the symposium will continue to be offered annually; next year’s Catalyst Symposium is already scheduled to take place in early May.
“I thought this year’s Catalyst Symposium was another great success. The talks from the visiting Fellows featured some amazing science from a wide range of fields,” Laub says. “I also think it’s fair to say that their interactions with the faculty, postdocs, and students here generated a lot of excitement and energy in our community, which is exactly what we hoped to accomplish with this symposium.”