Research Area: Human Disease

Investigating pathogens and their life cycles, for the benefit of society

Senior Desmond Edwards has an insatiable curiosity about how the human body works — and how diseases stop it from working.

Leah Campbell | School of Science
November 21, 2021

Desmond Edwards was a little kid when first learned about typhoid fever. Fortunately, he didn’t have the disease. He was looking at a cartoon public health announcement. The cartoon, produced by the Pan American Health Organization, was designed to educate people in his home country of Jamaica about the importance of immunizations for diseases like typhoid. The typhoid character in the cartoon was so unpleasant it gave him nightmares.

Edwards did have his fair share of hospital visits throughout his childhood. But, his own struggles with infection and illness, and those typhoid cartoon nightmares, became his inspiration for pursuing a career studying human disease. At age 6, Edwards was running impromptu baking soda experiments in repurposed glitter containers in his kitchen. Today, he is a senior at MIT, majoring in biology and biological engineering, thanks to a team of dedicated mentors and an insatiable curiosity about how the human body works — or, more accurately, how diseases stop it from working.

Finding a way into research

Edwards knew he wanted to do research but says he assumed that that was something you did after you got your degree. Imagine his surprise, then, upon arriving at MIT in 2018 and meeting classmates who not only had done research, but already had publications. Realizing that he could get a jump-start on his career, he sought out research opportunities and enrolled in the biology class 7.102 (Introduction to Molecular Biology Techniques) for his first-year Independent Activities Period. The class was specifically geared toward first-year students like him with no lab experience.

“It was a great first look at how research is done,” Edwards says of the class. Students took water samples from the Charles River and were expected to identify the strains of bacteria found in those samples using various biological techniques. They looked at the bacteria under a microscope. They examined how the samples metabolized different sources of carbon and determined if they could be stained by different dyes. They even got to try out basic genetic sequencing. “We knew where we were starting. And we knew the end goal,” says Edwards. The in-between was up to them.

Class 7.102 is taught by Mandana Sassanfar, a lecturer in biology and the department’s director of diversity and science outreach. For Sassanfar, the class is also an opportunity to find lab placements for students. In Edwards’ case, she literally led him to the lab of Assistant Professor Becky Lamason, walking up with him one evening to meet a postdoc, Jon McGinn, to talk about the lab and opportunities there. After Edwards expressed his interest to Lamason, she responded within 30 minutes. McGinn even followed up to answer any lingering questions.

“I think that was really what pushed it over the edge,” he says of his decision to take a position in the Lamason lab. “I saw that they were interested not only in having me as someone to help them do research, but also interested in my personal development.”

At the edges of cells and disciplines

The Lamason lab researches the life cycle of two different pathogens, trying to understand how the bacteria move between cells. Edwards has focused on Rickettsia parkeri, a tick-borne pathogen that’s responsible for causing spotted fever. This type of Rickettsia is what biologists call an obligate intracellular pathogen, meaning that it resides within cells and can only survive when it’s in a host. “I like to call it a glorified virus,” Edwards jokes.

Edwards gets excited describing the various ways in which R. parkeri can outsmart its infected host. It’s evolved to escape the phagosome of the cell, the small liquid sac that forms from the cell membrane and engulfs organisms like bacteria that pose a threat. Once it gets past the phagosome and enters the cell, it takes over cellular machinery, just like a virus. At this point of the life cycle, a bacterium will typically replicate so many times that the infected cell will burst, and the pathogen will spread widely. R. parkeri, though, can also spread to uninfected cells directly through the membrane where two cells touch. By not causing a cell to burst, the bacterium can spread without alerting the host to its presence.

“From a disease standpoint, that’s extremely interesting,” says Edwards. “If you’re not leaving the cell or being detected, you don’t see antibodies. You don’t see immune cells. It’s very hard to get that standard immune response.”

In his time in the lab, Edwards has worked on various projects related to Rickettsia, including developing genetic tools to study the pathogen and examining the potential genes that might be important in its life cycle. His projects sit at the intersection of biology and biological engineering.

“For me, I kind of live in between those spaces,” Edwards explains. “I am extremely interested in understanding the mechanisms that underlie all of biology. But I don’t only want to understand those systems. I also want to engineer them and apply them in ways that can be beneficial to society.”

Science for society

Last year, Edwards won the Whitehead Prize from the Department of Biology, recognizing students with “outstanding promise for a career in biological research.” But his extracurricular activities have been driven more by his desire to apply science for tangible social benefits.

“How do you take the science that you’ve done in the lab, in different research contexts, and translate that in a way that the public will actually benefit from it?” he asks.

Science education is particularly important for Edwards, given the educational opportunities he was given to help get to MIT. As a high schooler, Edwards participated in a Caribbean Science Foundation initiative called the Student Programme for Innovation in Science and Engineering. SPISE, as it’s known, is designed to encourage and support Caribbean students interested in careers in STEM fields. The program is modeled on the Minority Introduction to Engineering and Science program (MITES) at MIT. Cardinal Warde, a professor of electrical engineering, is himself from the Caribbean and serves as the faculty director for both MITES and SPISE.

“That experience not only kind of opened my eyes a bit more to what was available, what was in the realm of possibilities, but also provided support to get to MIT,” Edwards says of SPISE. For example, the program helped with college applications and worked with him to secure an internship at a biotech company when he first moved to the United States.

“If education falters, then you don’t replenish the field of science,” Edwards argues. “You don’t get younger generations excited, and the public won’t care.”

Edwards has also taken a leadership role in the MIT Biotechnology Group, a campus-wide student group meant to build connections between the MIT community and thought leaders in industry, business, and academia. For Edwards, the biotech and pharmaceutical industries play a clear role in disease treatment, and he knew he wanted to join the group before he even arrived at MIT. In 2019, he became co-director of the Biotech Group’s Industry Initiative, a program focused on preparing members for industry careers. In 2020, he became undergraduate president, and this year he’s co-president of the entire organization. Edwards speaks proudly of what the Biotech Group has accomplished during his tenure on the executive board, highlighting that they not only have the largest cohort ever this year, but it’s also the first time the group has been majority undergraduate.

Somehow, in between his research and outreach work, Edwards finds time to minor in French, play for the Quidditch team, and serve as co-president on the Course 20 Undergraduate Board, among other activities. It’s a balancing act that Edwards has mastered over his time at MIT because of his genuine excitement and interest in everything that he does.

“I don’t like not understanding things,” he jokes. “That applies to science, but it also extends to people.”

Stem Cell Research Zeroes in on Cancer

Collaborators investigate colon health with novel tools

Deborah Halber | Spectrum
November 9, 2021

In a building at the edge of the Massachusetts General Hospital (MGH) complex, Ömer Yilmaz, MD, and a group of pathology residents gather around a microscope. A resident reads from a chart: a growth was found in the intestine of a patient who had complained of abdominal pain.

Yilmaz, an MIT cancer researcher and a gastrointestinal pathologist, hoped a closer look at the tumor would reveal a noncancerous collection of fat cells or lymphoid cells.

It had taken a couple of days to prepare the biopsy. Somewhere in the hospital, the patient and her family were anxiously awaiting a diagnosis. Yilmaz leaned forward and adjusted the focus on the microscope.

On the tracks of cancer

If the long, twisting tube of the human digestive tract were stretched out straight, it would extend 30 feet, and its absorptive surface area is roughly comparable to the size of a tennis court. A significant chunk of that tube is the large intestine, an intricate place rife with microscopic structures called niches and crypts, evoking an underground cavern or the ocean floor. Besides the skin, the intestines are the body’s primary barrier against external invaders.

Yilmaz, an associate professor of biology at the Koch Institute for Integrative Cancer Research, believes certain cancers and diseases such as inflammatory bowel disease originate with a breakdown of the intestine’s protective barrier. Diet appears to affect intestinal stem cells; these cells can morph into a variety of cell types, and changes in stem cells can lead to cancer, but no one understands exactly how this occurs.

That’s where Yilmaz’s partnership with MIT biomedical engineer and chemist Alex Shalek comes in. Yilmaz and Shalek are both members of the MIT Stem Cell Initiative, which focuses on fundamental biological questions about benign and cancerous adult stem cells.

Shalek, a core member of the Institute for Medical Engineering and Science (IMES), a member of the Koch Institute, and an associate professor of chemistry, develops experimental and computational tools that provide researchers with detailed snapshots of what’s going on inside living cells at a moment in time. Some of these tools, Yilmaz hoped, would enable him to see how intestinal cells react when they encounter an influx of fat or are deprived of food for hours or days.

“In the past, people would have taken a piece of gut that had many different cell types and said, ‘What changes, on average, under different dietary conditions?’” Shalek says. His tools give him and Yilmaz more precise information, providing a window into the discrete molecular responses of individual cells within the colon.

The role of stem cells

Growing up in Battle Creek, Michigan, Yilmaz spent all his free time trailing after his father, a physician who had immigrated from Turkey. He’d make hospital rounds with his dad, visiting the pathology and radiology labs. As Yilmaz grew older, the two would talk about the mechanisms underlying disease.

After completing his MD/PhD at the University of Michigan, Yilmaz did his residency in pathology, the study of disease, at MGH. He began working at the Whitehead Institute with MIT biology professor David M. Sabatini, a pioneer in elucidating the mechanisms under-lying the regulation of growth and metabolism in mammals. Yilmaz had long been fascinated with stem cells’ seemingly miraculous ability to become any kind of cell the body needed. In adults, stem cells are relatively rare, best studied in bone marrow.

When scientists first found stem cells in the intestine in 2007, Yilmaz shifted his research focus. “As soon as intestinal stem cells were identified, I became interested in understanding how they are regulated by diet and aging,” he says.

“We know obesity elevates cancer risk in a wide range of tissues, including the colon, but we don’t know exactly how. And fasting regimens have been known to improve organ and tissue health, but this, too, is not well understood.”

To better study the transition from healthy to diseased cells in the colon, Yilmaz’s team generated colon tumors in mice that closely resemble human tumors. These colon tumors from mice or humans can be grown in culture, creating miniature three-dimensional tumors called organoids.

Subjecting the organoids to different conditions, Yilmaz and Sabatini found that in mice, age-related loss of stem cell function can be reversed by a 24-hour fast. Other studies looked at the type of high-fat diet leading to obesity. Yilmaz determined that a high-fat diet boosted the population of intestinal stem cells and generated even more cells that behaved like stem cells. These stem cells and stem-like cells are more likely to give rise to intestinal tumors.

What’s happening inside

In the microenvironment of the digestive system, the single layer of epithelial cells that line the colon die after only a few days of ferrying nutrients into the bloodstream and lymphatic system.

Stem cells sheltered in protected spaces with fanciful names like the crypts of Lieberkühn generate a hundred grams of new intestinal tissue every day. The source of all the epithelial cells as well as the cells of the villi, a velvety layer of fingerlike projections that line the intestine, stem cells repair and replace tissue continually assaulted by stomach acid, pancreatic enzymes, bile, fats, and bacteria.

Nearby cells guard the stem cells by secreting agents that fight off harmful bacteria, fungi, and viruses and help regulate the composition of the microbiome.

Most of the body’s stem cells, like those deep within bone marrow, are not nearly as prolific as intestinal stem cells, likely because there’s a risk associated with the stem cells’ ability to rapidly replace themselves: mutations.

At the heart of a cell’s behavior is its messenger RNA, or mRNA, the technology used in the Moderna and Pfizer Covid-19 vaccines. These mRNA vaccines teach cells how to make a protein that triggers an immune response to the virus. Each mRNA transcript, a single strand of RNA carrying a specific genetic instruction from the DNA in the nucleus to the cell’s protein-making machinery, determines which protein gets made to help support the cell’s activity.

“From a snapshot of all of the cell’s mRNA, its transcriptome, we can see how it is trying to respond to change,” Shalek says.

Shalek’s tools help him and Yilmaz measure the properties of multiple types of intestinal cells—immune cells, stem cells, and epithelial cells, to name a few—at once to see precisely how these otherwise invisible, minute features collectively orchestrate tissue-wide responses to external signals.

Sequencing a cell’s mRNA makeup requires smashing the cell open and collecting all of its transcripts. Shalek jokingly likened the process to an alien invader beaming human specimens up to a spaceship and investigating what’s happening inside them.

One of the methods Shalek helped develop tags each mRNA within a cell so that it can be traced back to its cell of origin even after it’s been ripped apart. The inexpensive, portable system, called Seq-Well, looks like an ice cube tray. Around the size of a stick of gum, it contains roughly a hundred thousand miniature wells, each approximately 50-by-50-by-50 microns.

Each cell is deposited into its own well, which contains a bead coated with uniquely barcoded DNA molecules; those DNA molecules are designed to latch onto mRNA and ignore the rest of the cell’s components. The wells are sealed and the cells broken apart. The beads are then extracted, processed, and analyzed, providing a record of each cell’s intentions in its last living moments.

The fact that the system can look simultaneously at thousands of individual cells of any type allows Shalek and Yilmaz to check the effect of nutrients on epithelial cells, immune cells, and stem cells all at once.

The Shalek lab is also developing screening tools that are particularly useful for exposing the Yilmaz lab’s organoids to hundreds of nutrients or drugs at one time, potentially reducing the effort needed to identify substances that boost or hinder stem cell function.

Already, Yilmaz and Shalek have used Seq-Well to identify an enzyme that could be a potential future target for a drug that would counter the negative effects of a high-fat diet on intestinal stem cells. More broadly, Yilmaz says, their collaboration is helping develop a very nuanced understanding of a very complex organ.

“Understanding that complexity is what has really driven our collaboration,” Yilmaz says. “Alex has developed the tools that enable us to dissect out individual cell populations and start to understand how environmental factors impact gene expression.”

“Scientists have spent the past 40 years delineating the genetic drivers of colon cancer, and we still have more to learn. But we’ve now entered the era in which we want to understand the impact of environmental and host factors,” Yilmaz says.

Yilmaz hopes to identify nutrients and metabolites that can enhance stem cell function to repair damage after injury, or to identify mechanisms that dampen tumor formation. In addition, biomarkers such as levels of certain substances in the blood could be a key to early intervention, he says.

“Can we identify which obese patients are more prone to developing colon cancer? If so, can we identify therapies that go after weaknesses in their tumors?”

Battling colon cancer

During the time Yilmaz spends at MGH, he looks at slide after slide of biopsied cells. Normal epithelial cells line up in a single, orderly row. After 15 years in medicine, the twisted appearance of diseased cells still shocks him. “You know, in most cases, the number one predictor of how bad a tumor is going to behave isn’t its genetic signature,” he says. “It’s how deep they invade into their organ of origin, whether they have spread to distant organs, and how bad they look under the microscope.” The cells of this patient’s tumor are misshapen, haphazardly stacked on top of each other.

The patient is in her forties. Yilmaz recalled that when he was a resident, colon cancer in a 40-year-old or 30-year-old was a rarity. He now sees such cases almost weekly. Colorectal cancer is among the top three leading causes of cancer-related deaths in the United States, according to the American Cancer Society. It’s expected to cause around 53,000 deaths during 2021. Yilmaz writes up his diagnosis: invasive cancer of the sigmoid colon. The patient’s oncologist will consult with Yilmaz, radiologists, and the surgical team to come up with a treatment plan.

Ultimately, Yilmaz wants to develop strategies to prevent and reduce the growth of tumors in the intestinal tract. The fact that increasingly younger patients are being diagnosed highlights, for him, the importance of diet. “It’s very worrisome,” he says. “We’re at the beginning of a trend where we’re going to see more and more young people afflicted with what can be a fatal disease if not caught early.” Diet could be an important place to start.

He says, “If you can prevent cancer, that’s the best treatment.”

Differences in T cells’ functional state determine resistance to cancer therapy

Researchers decipher when and why immune cells fail to respond to immunotherapy, suggesting that T cells need a different kind of prodding to re-engage the immune response.

Grace van Deelen
October 29, 2021

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in humans. Some patients with NSCLC receive a therapy called immune checkpoint blockade (ICB) that helps kill cancer cells by reinvigorating a subset of immune cells called T cells, which are “exhausted” and have stopped working. However, only about 35% of NSCLC patients respond to ICB therapy. Stefani Spranger’s lab at the MIT Department of Biology explores the mechanisms behind this resistance, with the goal of inspiring new therapies to better treat NSCLC patients. In a new study published on Oct. 29 in Science Immunology, a team led by Spranger lab postdoc Brendan Horton revealed what causes T cells to be non-responsive to ICB — and suggested a possible solution.

Scientists have long thought that the conditions within a tumor were responsible for determining when T cells stop working and become exhausted after being overstimulated or working for too long to fight a tumor. That’s why physicians prescribe ICB to treat cancer — ICB can invigorate the exhausted T cells within a tumor. However, Horton’s new experiments show that some ICB-resistant T cells stop working before they even enter the tumor. These T cells are not actually exhausted, but rather they become dysfunctional due to changes in gene expression that arise early during the activation of a T cell, which occurs in lymph nodes. Once activated, T cells differentiate into certain functional states, which are distinguishable by their unique gene expression patterns.

In order to determine why some tumors are resistant to ICB, Horton and the research team studied T cells in murine models of NSCLC. The researchers sequenced messenger RNA from the responsive and non-responsive T cells in order to identify any differences between the T cells. Supported in part by the Koch Institute Frontier Research Program, they used a technique called Seq-Well, developed in the lab of fellow Koch Institute member J. Christopher Love, the Raymond A. (1921) and Helen E. St. Laurent Professor of Chemical Engineering and a co-author of the study. The technique allows for the rapid gene expression profiling of single cells, which permitted Spranger and Horton to get a very granular look at the gene expression patterns of the T cells they were studying.

Seq-Well revealed distinct patterns of gene expression between the responsive and non-responsive T cells. These differences, which are determined when the T cells assume their specialized functional states, may be the underlying cause of ICB resistance.

Now that Horton and his colleagues had a possible explanation for why some T cells did not respond to ICB, they decided to see if they could help the ICB-resistant T cells kill the tumor cells. When analyzing the gene expression patterns of the non-responsive T cells, the researchers had noticed that these T cells had a lower expression of receptors for certain cytokines, small proteins that control immune system activity. To counteract this, the researchers treated lung tumors in murine models with extra cytokines. As a result, the previously non-responsive T cells were then able to fight the tumors — meaning that the cytokine therapy prevented, and potentially even reversed, the dysfunctionality.

Administering cytokine therapy to human patients is not currently safe, because cytokines can cause serious side effects as well as a reaction called a “cytokine storm,” which can produce severe fevers, inflammation, fatigue, and nausea. However, there are ongoing efforts to figure out how to safely administer cytokines to specific tumors. In the future, Spranger and Horton suspect that cytokine therapy could be used in combination with ICB.

“This is potentially something that could be translated into a therapeutic that could increase the therapy response rate in non-small cell lung cancer,” Horton says.

Spranger agrees that this work will help researchers develop more innovative cancer therapies, especially because researchers have historically focused on T cell exhaustion rather than the earlier role that T cell functional states might play in cancer.

“If T cells are rendered dysfunctional early on, ICB is not going to be effective, and we need to think outside the box,” she says. “There’s more evidence, and other labs are now showing this as well, that the functional state of the T cell actually matters quite substantially in cancer therapies.” To Spranger, this means that cytokine therapy “might be a therapeutic avenue” for NSCLC patients beyond ICB.

Jeffrey Bluestone, the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the University of California-San Francisco, who was not involved with the paper, agrees. “The study provides a potential opportunity to ‘rescue’ immunity in the NSCLC non-responder patients with appropriate combination therapies,” he says.

This research was funded by the Pew-Stewart Scholars for Cancer Research, the Ludwig Center for Molecular Oncology, the Koch Institute Frontier Research Program through the Kathy and Curt Mable Cancer Research Fund, and the National Cancer Institute.

Ushering discoveries from bench to bedside

Studying cancer in the Sharp lab helped Courtney JnBaptiste learn strategic thinking skills that he uses as a patent agent, transforming technology into successful biotech businesses.

Raleigh McElvery | Department of Biology
October 17, 2021

Courtney JnBaptiste PhD ’16 spent the first 19 years of his life on the idyllic Caribbean island of Saint Lucia, surrounded by clear waters, sandy beaches, and a robust agricultural community. His family owned their own farm, where they grew bananas and other crops for export. JnBaptiste and his six siblings spent hours each day after school and on the weekends helping to harvest the fruits of their labor. “We were better off than most, but it was a hard existence,” he says. “I had to fight to make something out of life. Where I am today is a big leap.”

He has since moved to the U.S. and completed his PhD at the MIT Department of Biology. Today, he uses the strategic thinking skills he learned during graduate school in his job as a patent agent, helping researchers protect their inventions and start biotech companies.

Despite his exceptional grades, JnBaptiste didn’t enjoy school growing up, and he’d often try to convince his parents that he didn’t need to go to class. His mother, a middle school teacher, was unfazed by his excuses and sent him off to school most days. Despite his protests, JnBaptiste understood his mother’s motto that “education is the key to success.” He knew he’d need good academic standing and self-motivation to attain the financially-stable life he envisioned.

During high school, cable TV became available to his community for the first time, and he was overwhelmed by the deluge of information. He became hooked on Animal Planet and Discovery Channel, and decided that he wanted to be like Jeff Corwin, a biologist, wildlife conservationist, and TV personality. JnBaptiste knew he’d need a college education to reach his career aspirations, and — due to its proximity and promise of opportunity — the U.S. seemed like an ideal destination.

He was accepted to Bethune-Cookman University in Florida and declared a major in biology. He was awarded an environmental research grant, which allowed him to spend several semesters studying the snail populations in Blue Spring State Park. But a summer internship at the University of Kansas Medical Center was what ultimately convinced him to pursue molecular biology rather than environmental sciences. During his junior year, a new biochemistry professor arrived: Christopher Ainsley Davis, a former postdoc in the lab of Cathy Drennan at the MIT Department of Biology.

“When the two of us spoke, he said something that shocked me,” JnBaptiste recalls. “He told me, ‘You’re good enough for MIT and you should apply to their summer research program.’ That just blew my mind. I never thought I was of the MIT caliber — no one had ever challenged me like that before.”

At Davis’ urging, JnBaptiste applied to the MIT Summer Research Program in Biology (MSRP-Bio), and was placed in the lab of Nobel laureate Phil Sharp. In the 1970s, Sharp had co-discovered splicing, a molecular process that happens after DNA has been transcribed into RNA. Segments of the RNA strand are removed, and the remaining parts are stitched back together and translated into proteins that perform vital functions inside the cell.

Two people at a lab bench
JnBaptiste (left) completed his PhD research in the lab of Phil Sharp (right).

Under the supervision of graduate student and postdoc mentors, JnBaptiste spent the summer of 2009 investigating the role that RNA splicing plays in cancer. “It was the best time of my life,” he says. “I just I loved it. I loved the environment. I loved the lab. I loved MIT. And that experience had a profound impact on me.”

He enjoyed campus so much that he returned just one year later to begin his PhD. He was looking forward to returning to the lab bench, but what he didn’t anticipate was that his first semester of classes would be the most rigorous education he’d ever received. He excelled in biochemistry, but found 7.52 (Graduate Genetics) especially difficult. “It was the first time I’d ever failed an exam,” he recalls.

With the help of mentors, classmates, and tutors, JnBaptiste passed genetics and moved on to the stage of his PhD that he was most excited about: lab rotations. After testing out a few different research groups, he ultimately decided to return to the Sharp lab. In his own words: “It was home.”

JnBaptiste’s thesis project focused on a type of RNA known as microRNA (miRNA), which is never translated into a protein. Instead, it remains in its single-stranded RNA form and helps regulate gene expression. The Sharp lab found that removing all the miRNAs from adult cells prompted dramatic activation of embryonic genes. These genes are typically turned off in adult cells, and only expressed during early development when rapid cell division is required. But they can also be hijacked during cancer to create tumors.

JnBaptiste was surprised to find that adding the miRNAs back into the cells didn’t shut down these embryonic genes. In fact, restoring the miRNAs made the cells divide even more rapidly and increased their ability to form tumors — suggesting “global miRNA restoration” would not be a viable approach to treat cancer.

“This model that we developed showed miRNAs control a very important network in the context of both development and cancer,” JnBaptiste explains. “Cancer occurs when normal cellular processes go awry, so understanding those fundamental molecular interactions is critical to fighting the disease.”

By the time he graduated from MIT in 2016, JnBaptiste knew he enjoyed science, but didn’t have ambitions to run his own lab. Instead, he was curious about how lab experiments and research questions engender companies.

When he was still an MSRP-Bio student, JnBaptiste had met an intellectual property lawyer who’d come to speak on campus. He’d been saving her business card ever since, and reached out to her as his time at MIT was drawing to a close. With her assistance, JnBaptiste was offered a job as a scientific advisor at Goodwin Procter, the international law firm where she worked.

JnBaptiste has since transitioned to a similar role as a patent agent at Pabst Patent Group. There, he collaborates with lawyers to write patents protecting new research technology. While scientists are focused on the minutia of their day-to-day lab experiments, JnBaptiste is tasked with understanding the bigger picture, and how those experiments might lay the foundation for successful businesses that could revolutionize therapeutic approaches.

“As a grad student at MIT, I learned a lot about what it takes to be a strategic thinker in science,” JnBaptiste says. “People like my mentor, Phil Sharp, not only recognize a discovery, they look beyond it to envision its future potential as the next biotech company. That’s a skill I’m still honing as I work to develop my business acumen.”

Looking back at his career trajectory thus far, JnBaptiste is struck by the “beauty and diversity” that comes with earning a degree in biology. “Follow your passions,” he advises, “and surround yourself with people who can see the potential and value in you — even when you cannot yet see it yourself.”

Posted: 10.17.21
Top photo: Elisabeth Sherwin/Hello Headshots
Sara Prescott

Education

  • PhD, 2016, Stanford University School of Medicine
  • BA, 2008, Molecular Biology, Princeton University

Research Summary

Our bodies are tuned to detect and respond to cues from the outside world and from within through exquisite collaborations between cells. For example, the cells lining our airways communicate with sensory neurons in response to chemical and mechanical signals, and evoke key reflexes such as coughing. This cellular collaboration protects our airways from damage and stabilizes breathing, but can become dysregulated in disease. Despite their vital importance to human health, fundamental questions about how sensory transduction is accomplished at these sites remain unsolved. We use the mammalian airways as a model system to investigate how physiological insults are detected, encoded, and addressed at essential barrier tissues — with the ultimate goal of providing new ways to treat autonomic dysfunction.

Awards

  • Warren Alpert Distinguished Scholars Award, 2021
  • Life Sciences Research Foundation Fellowship, 2018
Probing pathogen spread during a global pandemic

Bailey Bowcutt investigated COVID-19 cases in rural Wyoming before coming to MIT for the summer and applying her knowledge to a new cellular invader.

Raleigh McElvery
July 23, 2021

The first time Bailey Bowcutt saw a lab it was nothing like she expected. Rather than a stark, sterile setting with sullen figures floating around like ghosts in white lab coats, the atmosphere was cordial and the dress casual. Some scientists even sported vibrant shirts with Marvel characters. A high school senior on a class field trip, Bowcutt couldn’t have predicted that the next time she’d set foot in the Wyoming Public Health Laboratory she’d no longer be a visitor, but a researcher performing diagnostic testing during a global pandemic. Now, as COVID-19 restrictions begin to lift, she’s taking the research tools she’s learned to Cambridge, Massachusetts to complete the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio) and investigate how other types of pathogens spread.

Growing up in rural Wyoming, Bowcutt had little exposure to science because there were few research institutes close by. But watching family members suffer from gastrointestinal illness and other infections spurred her to pursue a degree in microbiology at Michigan State University (MSU). Shortly after she arrived on campus in the fall of 2019, she joined Shannon Manning’s lab studying antibiotic resistance in cattle.

Cows are prone to contracting a bacterial infection of the udder called mastitis. (In humans, a similar inflammation can occur in breast tissue.) Manning’s lab is looking at how antibiotic treatments affect the bovine gut microbiome and emergence of antibiotic resistance genes. Bowcutt’s role was to help identify these super bugs inside the cows’ gastrointestinal tracts.

“I got to go to the farm to take samples, which involved a glove that goes all the way up to the shoulder and some invasive maneuvers inside cows,” she explains. “Luckily, I was just the bag holder!”

Intimate sample collection aside, Bowcutt was excited about the work because it combined agriculture and human health research to solve issues plaguing rural communities. But her time on the farm was cut short when COVID-19 cases climbed in early 2020. She headed back to her home in Wyoming to begin remote MSU classes and, reminiscing about her field trip to the Wyoming Public Health Laboratory, reached out to the director to see if there were any internship opportunities.

“I’d barely learned how to do science at that point, but they needed people who could handle a pipette, so they took me,” she says. “I ended up being one of the first people there helping with COVID research, and I stayed for about a year-and-a-half while I took online classes.”

The lab would receive nasopharyngeal swabs from COVID-19 patients, and Bowcutt’s first task was to help extract RNA from the samples. Later, she transitioned to another project, which required performing PCR on untreated wastewater samples to glean a population-level understanding of where COVID-19 outbreaks were occurring.

She began toying with the idea of pursuing a PhD, but wasn’t sure what it would entail. So, in early 2021, she started Googling summer science programs and stumbled on BSG-MSRP-Bio. She was accepted, and paired with one of the very labs that had caught her eye online: assistant professor Becky Lamason’s group.

Microscopy image of parasites rocketing around inside cells
Listeria monocytogenes (yellow) rocket around their host cells (outlined in cyan) before ramming through the host’s membrane and that of its neighbor, forming a protrusion that is engulfed by the recipient cell. Image by Cassandra Vondrak.

“If you’ve ever seen microscopy pictures from the Lamason lab, they’re just so beautiful,” Bowcutt explains. Beautiful, yes — but she would soon learn these snapshots capture a chilling cellular invasion and molecular heist.

The Lamason lab watches malicious bacteria as they hijack molecules in human host cells to build long tails, rocket around, and punch through the cell membrane to spread. Bowcutt’s mentor, graduate student Yamilex Acevedo-Sánchez, focuses on the food-borne bacterium Listeria monocytogenes, which targets the gastrointestinal tract. Acevedo-Sánchez’s research aims to understand the host cell pathways that Listeria commandeers to move from one cell to the next in a process called cell-to-cell spread.

Together, Acevedo-Sánchez and Bowcutt are investigating several proteins in the human host cell involved in cellular transport and membrane remodeling (Caveolin-1, Pacsin2, and Fes), which could regulate Listeria’s spread. Over the summer, the duo has been adjusting the levels of these proteins and observing what happens to Listeria’s ability to move from cell-to-cell.

Bowcutt spends most of her days doing Western blots; growing Listeria and mammalian cells; and combining immunofluorescence assays with fixed and live cell microscopy to take her own striking microscopy images and movies of the parasites.

“I expected the work environment at MIT to be very intense, but everyone has been really friendly and willing to answer questions,” she says. “Some of my favorite experiences have just been in the lab while everyone is bustling around. It’s a welcome change after so much COVID-19 isolation.”

Now that the COVID-era occupancy restrictions have lifted, Bowcutt’s lab bench neighbor is Lamason herself. “She’s next to me doing experiments all the time,” Bowcutt explains, “which is cool because she’s really engaging with the research in the same way we are.”

Bowcutt says her summer experience has given her some much-needed practice designing research questions and devising the experiments to answer them. She’s also acquired a new skill she didn’t anticipate: interpreting ambiguous results and developing follow-up experiments to clarify them.

These days, the prospect of a PhD seems much less intimidating. In fact, the Lamason lab has done more than simply pique Bowcutt’s interested in fundamental biology research. She’s now considering ways to combine her microbiology skills with her interest in rural health care.

“I didn’t expect to see this much growth in myself,” she says, “and I know it’s making me a better scientist. I’m excited to return to MSU in the fall because I feel like I can do so much more now — and I would totally do it again.”

Hernandez Moura Silva

Education

  • PhD, 2011, University of São Paulo Heart Institute
  • MSc, Molecular Biology, 2008, University of Brasilia
  • BS, 2005, Biology, University of Brasilia

Research Summary

By utilizing an innovative and intersectional approach, our lab main goal is to reveal fundamental immune-related pathways that modulate organ and tissue physiology. Our work will help to develop new strategies to tune these molecular pathways in health and disease, leading to the development of much-needed therapeutic approaches for human diseases.

Awards

  • CAPES Thesis Award – Brazil, 2012
Lessons from teaching about the pandemic in real-time

Covid-19 class taps experts to help students and the public avoid misinformation as the crisis evolves.

Raleigh McElvery | Department of Biology
May 21, 2021

Just a few months after the Covid-19 pandemic took hold, Alan Grossman was already mulling over an idea for a new class to help people make sense of the virus. As head of MIT’s Department of Biology, he was aware of the key role fundamental research would play in the coming months. From RNA viruses and genomic sequencing to antibodies and vaccines, MIT students and the general public would need reliable scientific information to understand the evolving situation — and discern fact from fiction.

Not long after, the thoughts he’d feverishly scribbled on paper scraps scattered around his house began to take shape. With the support of the MIT School of Science, Accessibility Office, MIT Video Productions, and others around the institute, the Department of Biology added a new fall subject to the course catalog: 7.00 (Covid-19, SARS-CoV-2 and the Pandemic). Undergraduates could take the class for credit, as notable researchers stepped up to the virtual podium to share their expertise in front of a public livestream.

Grossman brought his nascent plans to associate department head and Whitehead Institute for Biomedical Research Member Peter Reddien, and together the two brainstormed individuals who might be willing to lead the class and queue speakers. They reached out to professor of biology and Whitehead Institute Member Richard Young, who served as an advisor to the World Health Organization and National Institutes of Health when a different virus of unknown origins was spreading — HIV. Young was also quick to mount a collaborative research campaign against SARS-CoV-2, the virus that causes Covid-19.

“I give Alan a lot of credit,” Young says. “He thought that it was the responsibility of the department to take the lead in filling the Covid-19 knowledge niche, and asked me if I would take this on and find a partner.”

Young contacted Ragon Institute Associate Director Facundo Batista, a world-class expert in immunology and infectious disease. Batista recalls being hesitant at first to co-lead the class; he couldn’t fathom condensing the global emergency into a single course. “But then I realized that the onslaught of information was the very reason we needed to organize this class — to help students and the public avoid misinformation,” he says. “We were filling a gap that the whole world was experiencing.”

Together, Batista and Young generated a list of 14 experts in an array of pandemic-related areas, including Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, David Baltimore of Caltech, and Kizzmekia Corbett of the National Institutes of Health. Each geared their lecture toward MIT undergraduates with a minimal biology background, and defined key terms and concepts so non-biologists watching the livestream could follow along as well.

Although Batista and Young agree that remote learning pales in comparison to in-person classes, the livestream format opened the talks up to thousands more viewers, and allowed the speakers to present their work without the need for travel. The recordings of each Tuesday lecture were posted on the Department of Biology’s website shortly thereafter, permitting asynchronous viewing for people around the world. The livestream audience regularly exceeded 1,000, and the YouTube views for each recording ranged from 4,000-97,000 and climbing. In many cases, the week’s topic fortuitously coincided with current events. For instance, Corbett spoke about vaccine development just days after the results of Pfizer-BioNTech’s first clinical trial were announced. As one of the NIH scientists who collaborated with Moderna to design another important mRNA-based vaccine, Corbett was able to discuss her reaction to the news and her expectations for Moderna’s imminent clinical trial results.

In addition to the livestream audience, each week roughly 300 MIT undergraduates would enter the Zoom room and get the opportunity to ask questions during the Q&A. Participation was unusually high, Young and Batista recall, thanks to the recitation sessions led by graduate student and teaching assistant Lena Afeyan. Afeyan would walk the students through the fundamentals of molecular biology, virology, and any other topics slated to feature heavily in the upcoming lecture. She also invited trainees and medical residents from various institutions to attend, in order to introduce students to the next generation of scientists and health-care professionals. The supplementary reading materials from these sessions are still available online, so biology teachers and other members of the public can access them.

“When I heard that this class was being put together, I hoped I could help make the content more accessible for the students and anyone else joining us,” Afeyan says. “The responses we got were overwhelming. It was incredible to hear from so many teachers, researchers, and alums across the world who watched the course every week.”

Even today, Afeyan, Young, and Batista continue to receive international kudos from scientists and non-scientists alike. At one point, Young was even interviewed by a radio station in Tasmania about the course.

“I learned a lot from 7.00 — not only about Covid-19, but about immunology and biology in general,” says Lucas Marden, a first-year undergraduate who enrolled in the class. “I particularly enjoyed the focus on the real-world response to the pandemic. We learned about everything from designing and developing different tests, treatments, and vaccines, to the scale-up of these technologies. The scientific community’s response to Covid-19 has been incredibly impressive, and I loved learning about it from the people at the forefront of their fields.”

Now, Grossman says, the department is planning to offer the class again this coming fall. “The initial idea stemmed from the need to share clear and reliable information about the pandemic as it began spreading,” he explains. “Although we’ve been living with Covid-19 for over a year now, that need is still present today — perhaps more so as we continue to learn what it will take to tame the virus.”

The next iteration of 7.00 will begin in September, and likely feature some of the same speakers and topics, along with new experts in areas that have recently emerged, such as the evolving viral variants. By arming the MIT community and the public with information from leading experts, Grossman, Batista, Young, and Afeyan hope to help the world navigate this pandemic — and prevent the next one.

Childhood hobbies jump-start a research career

MIT Biology junior Eduardo Canto tinkered with science long before he started studying Treacher Collins syndrome in the Calo lab.

Saima Sidik | Department of Biology
May 19, 2021

In seventh grade, Eduardo Canto wanted a dog. His mom said no, though. She didn’t want to spend her days vacuuming fur. They reached a compromise: Canto was allowed to have pet fish. Soon Canto’s disappointment with his new pets turned to curiosity. While he couldn’t train the fish to sit or roll over, he decided that breeding the fish could be a fun pastime.

An internet search told Canto that some aquarists use dried Indian almond leaves, a traditional Asian herbal remedy, to stimulate fish breeding, although no one is quite sure how the leaves do this. However, finding Indian almond leaves presented a problem for a kid without an Amazon account living far from the tree’s native habitat. On a whim, Canto picked up some similar-looking leaves in a park near his house in Puerto Rico. He knew they weren’t from an Indian almond tree, but he put them in the tank anyhow, just to see what would happen. A few days later, he noticed a collection of eggs attached to the bottom of a leaf!

Canto often took on little experiments like this, which caused his grandfather to predict early on that he would have a scientific career. Eight years after the breeding endeavor, Canto is fulfilling his grandfather’s prediction by studying Course 7 (Biology) at MIT, where he’s currently in his third year of a bachelor’s degree. Once again, fish have come into Canto’s life — he’s working in Eliezer Calo’s lab, where researchers use zebrafish to study a genetic disorder called Treacher Collins syndrome, which causes deformities in eyes, ears, cheekbones, and chins.

Throughout middle school and high school, Canto dipped his toes into many scientific disciplines. School science fairs motivated him to build a dry ice-powered trolley, a solar-powered water heater, and start a vegetable garden.

Sometimes, he admits, his motivation for joining science clubs wasn’t lofty. “I joined the math club because I got to miss a day of school every year for their annual competition,” he says with a laugh. But he also talks excitedly about his early experiments, particularly in biology. “I’ve always loved working with my hands,” he says.

Canto’s father, a medical doctor, encouraged his son’s interest by letting Canto shadow him at work. He also started a molecular biology summer program at Canto’s high school that taught students how to pipette and do simple experiments. By the time Canto applied to college, he was convinced he wanted to study biology, and MIT drew his attention because of its reputation as a top science school with excellent biology teachers. He knew it was the right choice for him when he attended Campus Preview Weekend, and found a large Puerto Rican community ready to welcome him. Even far from the island, he felt at home.

Canto has kept up with his roots since joining MIT by playing on a soccer team for Puerto Rican students. He’s also become part of a new community in a lab run by Eliezer Calo — who is a Puerto Rican himself. The lab is interested in ribosomes, the molecular machines that build proteins. Treacher Collins syndrome arises when cells can’t make ribosomes properly, and Canto wants to understand why that is.

Before Canto joined the Calo lab, the group had already started studying a protein called DDX21 that’s involved in making ribosomes in both humans and zebrafish. When genetic mutations in zebrafish cause DDX21 to go to the wrong part of the cell, the fish develop jaw deformations that mirror Treacher Collins syndrome. The Calo lab thinks cells with mislocalized DDX21 probably don’t produce ribosomes as well as normal cells, but they’re still testing this hypothesis.

Canto wants to probe the relationship between DDX21 and Treacher Collins syndrome further, but fish reproduce slowly, so they’re not ideal organisms for his research. Instead, he’s built a strain of Escherichia coli bacteria that carry DDX21 in place of the equivalent bacterial gene. DDX21 helps these bacteria survive the stress associated with cold temperatures, so without it, the bacteria will die in the cold. Canto hopes to take advantage of this trait by finding small molecules that stop the bacteria from growing at low temperatures — just like a DDX21 mutation would. Studying how these molecules bind DDX21 will help him understand which parts of this protein are important for its function.

The possibility that this work will one day reveal how Treacher Collins syndrome develops in patients is rewarding to Canto, and in fact he hopes helping patients will soon become his life’s focus. He wants to attend medical school, and eventually become a doctor. The human physiology class he took last semester was one of his favorites, even though it was over Zoom due to the COVID-19 pandemic. Becoming a doctor will let him help others while studying topics he finds fascinating. “Medicine is like biology on steroids!” he says.

And who knows — one day after he’s a doctor, maybe he’ll even get that pet he’s always wanted. But unlike Canto’s interest in biology, some of his interests have evolved over time. These days, he prefers cats over dogs.

Photo credit: Saima Sidik
Posted: 5.19.21
Olivia Corradin

Education

  • PhD, 2015, Case Western Reserve University
  • BS, 2010, Biochemistry, Marquette University

Research Summary

Our lab studies genetic and epigenetic variation that contributes to human disease by disrupting gene expression programs. We utilize biological insights into the mechanisms of gene regulation in order to determine the impact of disease-associated variants on cellular function. We aim to identify actionable insights into disease pathogenesis by studying the confluence of genetic and epigenetic risk factors of human diseases, including multiple sclerosis and opioid use disorder.

Awards

  • NIH Director’s Pioneer Award Program Avenir Award, 2017