Cold Spring Harbor Laboratory

Christopher Vakoc with graduate student Junwei Shi. Photo by Gina Motisi/ CSHL.

By Daniel Dunaief

It is the type of miraculous conversion that doesn’t involve religion, and yet it may one day lead to the answer to passionate prayers from a group of people on a mission to help sick children.

Researchers in the lab of Professor Christopher Vakoc at Cold Spring Harbor Laboratory have been working tirelessly to understand the fundamental biology of Rhabdomyosarcoma, or RMS, which is a type of connective tissue cancer that afflicts between 400 and 500 people each year in the United States, with more than half receiving the diagnosis before they turn 10 years old.

As a part of her PhD research, Martyna Sroka searched for a way to convert the processes involved in this cancer into something benign.

Using a gene editing tool enhanced by another former member of Vakoc’s lab, Sroka disrupted a signal she had spent years trying to find in a protein called NF-Y, causing cancerous cells in a dish to differentiate into normal muscle cells, a conversion that offers future promise for treatment.

Sroka, who is now working as a scientist in a biotechnology company focused on the development of oncology drugs, described how RMS cells look small and round in a microscope. After disrupting this protein, the “differentiated cells become elongated and spindle-like, forming those long tubular structures,” she explained.

She often grew cells on plastic dishes and the differentiated RMS cells spanned the entire diameter of a 15 centimeter plate, providing a striking visual change that highlighted that conversion.

While this research represents an important step and has created considerable excitement in the scientific community and among families whose philanthropic and fundraising efforts made such a discovery possible, this finding is a long way from creating a new treatment.

Other research has indicated that disrupting NF-Y could harm normal cells. A potential therapeutic alteration in NF-Y could be transient and would likely include follow ups such as a surgical, radiation or biological approach to remove the converted RMS cells, Vakoc explained.

Nonetheless, the research, which was published in August in the prestigious Proceedings of the National Academy of Sciences, offers a potential roadmap for future discoveries.

“It was a long journey and being able to put the pieces of the puzzle together into a satisfying mechanism, which might have broader implications not only for our basic understanding of the biology of the disease but also for potential novel therapeutic approaches, was extremely exciting and rewarding,” said Sroka.

“It’s great to see so much excitement in the pediatric cancer field, and I am hoping that with time it will translate to much-needed novel therapeutic options for pediatric patients.”

The search

Cancer signals typically involve rewiring a cell’s genetic material, turning it into a factory that creates numerous, unchecked copies of itself.

Sroka and Vakoc were searching for the kind of signal that might force those cells down what they hope is a one-way differentiation path, turning those otherwise dangerous cells into more normal muscle cells that contract.

To find this NF-Y gene and the protein it creates, Sroka, who started working in Vakoc’s lab in the summer of 2017, screened over a 1,000 genes, which Vakoc described as a “heroic effort.”

Encouraged by this discovery and as eager to find new clinical solutions as the families who helped support his research, Vakoc recognizes he needs to strike a balance between trumpeting this development and managing expectations.

Interactions with the public, including families who have or are confronting this health threat, “comes with a lot of responsibility to make sure we’re being as clear as possible about what we’ve done and what have yet to do,” said Vakoc. “It’s going to be a long and uncertain road” to come up with new approaches to this cancer.

Funding families

Some of the families who provided the necessary funding for this work shared their appreciation for the commitment that Vakoc, Sroka and others have made.

“We are very excited about the newest paper [Vakoc and Sroka] published,” said Phil Renna, the Senior Director of Communications at CSHL and Director of the Christina Renna Foundation, which he and his wife Rene formed when their daughter Christina, who passed away at the age of 16, battled the disease. The Christina Renna Foundation has contributed $478,300 to Vakoc’s lab since 2007.

“In just a few short years, he has made a major leap forward. This lights the path of hope for us and our cause,” said Renna.

Renna explained that the lab has had numerous inquiries about this research. He and others recognize that the search for a cure or treatment involves “tough, grinding work” and that considerable basic research is necessary before the research can lead to clinical trials or new therapeutics.

Paul Paternoster, whose wife Michelle succumbed to the disease and who has raised funds, called Vakoc and Sroka “brilliant and incredibly hard working,” and suggested the exciting results “came as no surprise.”

He is “extremely pleased” with the discovery from the “standpoint of what it can lead to, and how quickly it was discovered.”

Paternoster, President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, suggested that this strategy can have implications for other soft tissue sarcomas as well.

The next steps

To build on the discoveries Sroka made in his lab, Vakoc plans to continue to use a technique Junwei Shi, another former member of his lab, developed after he left CSHL and joined the University of Pennsylvania, where he is now a tenured professor.

Shi, whom Vakoc called a “legend” at CSHL for honing the gene editing technique called CRISPR for just this kind of study, is also a co author in this paper.

In future research, Vakoc’s lab plans to take the screens Sroka used to find NF-Y to search to the entire human genome.

“That’s how the family tree of science operates,” said Vakoc. Shi “made a big discovery of CRISPR and has since continued to create new technology and that he is now sharing back” with his lab and applying it to RMS. Additionally, Vakoc plans to expand the testing of this cellular conversion from plastic dishes to animal models

Shi, who worked in Vakoc’s lab from 2009 to 2016 while he earned his PhD at Stony Brook University, expressed satisfaction that his work is paying dividends for Vakoc and others.

“It just feels great that [Vakoc] is still using a tool that I developed,” said Shi in an interview. Many scientists in the field are using it, he added.

For Shi, who was born and raised in southern China, working at Cold Spring Harbor Laboratory fulfilled a lifelong dream.

He recalled how he retrieved data one Saturday morning that indicated an interesting pattern that might reveal the power of a new methodology to improve CRISPR screening.

When Vakoc came to the lab that morning, Shi shared the data, which was a “whole turning point,” Shi said. 

Shi said he appreciates how CSHL has been “a home for me,” where he learned modern molecular biology and genetics.

When he encounters a problem in his lab, he often thinks about how Vakoc would approach it. Similarly, Vakoc suggested he also reflects on how his mentor Gerd Blobel, who is a co-author on the recent paper and is at the Children’s Hospital of Philadelphia, would respond to challenges.

As for the family members of those eager to support Vakoc, these kinds of scientific advances offer hope.

When he started this journey, Renna suggested he would feel satisfied if researchers developed a cure in his lifetime. This paper is the “next step in a marathon, but it makes us very excited,” he said.

To share the encouraging results from Vakoc’s lab with his daughter, Renna tacked up the PNAS paper to the wall in Christina’s bedroom.


A Jamaican fruit bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

By Daniel Dunaief

Popular in late October as Halloween props and the answer to trivia questions about the only flying mammals, bats may also provide clues about something far more significant.

Despite their long lives and a lifestyle that includes living in close social groups, bats tend to be resistant to viruses and cancer, which is a disease that can and does affect other mammals with a longer life span.

Armin Scheben

In recent work published in the journal Genome Biology and Evolution, scientists including postdoctoral researcher at Cold Spring Harbor Laboratory and first author Armin Scheben, CSHL Professor and Chair of the Simons Center for Quantitative Biology Adam Siepel, and CSHL Professor W. Richard McCombie explored the genetics of the Jamaican fruit bat and the Mesoamerican mustached bat.

By comparing the complete genomes for these bats and 13 others to other mammals, including mice, dogs, horses, pigs and humans, these scientists discovered key differences in several genes.

The lower copy number of interferon alpha and higher number of interferon omega, which are inflammatory protein-coding genes, may explain a bat’s resistance to viruses. As for cancer, they discovered that bat genomes have six DNA repair and 33 tumor suppressor genes that show signs of genetic changes.

These differences offer potential future targets for research and, down the road, therapeutic work.

“In the case of bats, we were really interested in the immune system and cancer resistance traits,” said Scheben. “We lined up those genomes with other mammals that didn’t have these traits” to compare them.

Scheben described the work as a “jumping off point for experimental validation that can test whether what we think is true: that having more omega than alpha will develop a more potent anti-viral response.”

Follow up studies

This study provides valuable potential targets that could help explain a bat’s immunological superpowers that will require further studies.

“This work gives us strong hints as to which genes are involved, but fully understanding the molecular biology will require more work” explained Siepel.

In Siepel’s lab, where Scheben has been conducting his postdoctoral research since 2019, he is using human cell lines to see whether adding genetic bat elements makes them more effective in fighting off viral infections and cancer. He plans to do more of this work with mice, testing whether these bat variants help convey the same advantages in live mice.

Armin Scheben won the German Academic International Network Science Slam competition with his presentation on bat genomics.

Siepel and Scheben have discussed improving the comparative analysis by collecting information across bats and other mammals of tissue-specific gene expression and epigenetic marks which would help reveal changes not only in the content of DNA, but also in how genes are being turned on and off in different cell types and tissues. That could allow them to focus more directly on key genes to test in mice or other systems.

Scheben has been collaborating with CSHL Professor Alea Mills, whose lab has “excellent capabilities for doing genome editing in mice,” Scheben said.

Scheben’s PhD thesis advisor at the University of Western Australia, Dave Edwards described his former lab member’s work as “exciting.”

Edwards, who is Director of the UWA Centre for Applied Bioinformatics in the School of Biological Sciences, suggested that Scheben stood out for his “ability to strike up successful collaborations” as well as his willingness to mentor other trainees.

Other possible explanations

While these genetic differences could reveal a molecular biological mechanism that explains the bat’s enviable ability to stave off infections and cancer, researchers have proposed other ways the bat might have developed these virus and cancer fighting assets.

When a bat flies, it raises its body temperature. Viruses likely prefer a normal body temperature to operate optimally. 

Bats are “getting fevers without getting infections,” Scheben said.

Additionally, flight increases the creation of reactive oxygen species, which the bat needs to control on an ongoing basis.

At the same time, bats produce fewer inflammatory cytokines, which helps prevent them from having a runaway immune reaction. Some researchers have hypothesized that bats clear reactive oxygen species more effectively than humans.

A ‘eureka’ moment

The process of puzzling together all the pieces of DNA into individual chromosomes took considerable time and effort.

A Mesoamerican mustached bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

Scheben spent over 280,000 CPU hours chewing through thousands of genes in dozens of species on the CSHL supercomputer called Elzar, named for the chef from the cartoon “Futurama.” Such an effort would have taken eight years on a modern day personal computer.

During this effort, Scheben saw this “stark effect,” he said. “We had known that bats had lost some interferon alpha. What astounded me was that some bats had lost all alpha” while they had also raised interferon omega. That was the moment when he realized he found something novel and bat specific.

Scheben recognized that this finding could be one of many that lead to a better understanding of the processes that lead to cancer.

“We know that it’s unlikely that a single set of genes or a small set of genes such as we identified can fully explain the diversity of outcomes when it comes to a complex disease like cancer,” said Scheben.

A long journey

A resident of Northport, Scheben grew up in Frankfurt, Germany. He moved to London for several years, which explains his use of words like “chuffed” to describe the excitement he felt when he received a postdoctoral research offer at Cold Spring Harbor Laboratory.

When he was young, Scheben was interested in science despite the fact that classes were challenging for him.

“I was pretty poor in math and biology, but I liked doing it,” he said.

Outside of work, Scheben enjoys baking dense, whole wheat German-style bread, which he consumes with cheese or with apple, pear and nuts, and also hiking.

As for his work, which includes collaborating with CSHL Professor Rob Martienssen to study the genomes of plants like maize that make them resilient amid challenging environmental conditions, Scheben suggested it was the “best time to be alive and be a biologist” because of the combination of new data and the computational ability to study and analyze it.

Scheben recognized that graduate students in the future may scoff at this study, as they might be able to compare a wider range of mammalian genomes in a shorter amount of time.

Such a study could include mammals like naked mole rats, whales and elephants, which also have low cancer incidence and long lifespans.

A scene from 'Oppenheimer'

By Daniel Dunaief

Researchers at Brookhaven National Laboratory, Cold Spring Harbor Laboratory and Stony Brook University joined the chorus of moviegoers who enjoyed and appreciated the Universal film Oppenheimer.

“I thought the movie was excellent,” said Leemor Joshua-Tor, Professor and HHMI Investigator at Cold Spring Harbor Laboratory. “It made me think, which is always a good sign.”

Yusuf Hannun, Vice Dean for Cancer Medicine at Stony Brook University, thought the movie was “terrific” and had anticipated the film would be a “simpler” movie.

Jeff Keister, leader of the Detector and Research Equipment Pool at NSLS-II at Brookhaven National Laboratory, described the movie as “interesting” and “well acted.”

Joshua-Tor indicated she didn’t know anything about Robert Oppenheimer, the title character and leader of the Manhattan Project that built the atomic bomb. She “learned lots of new things” about him, she wrote. “I knew he was targeted by McCarthy-ism, but didn’t realize how that came about and the details.”

Keister also didn’t know much about Oppenheimer, who was played by actor Cillian Murphy in the film. “Oppenheimer seemed to quietly struggle with finding his role in the story of the development of the atomic bomb,” Keister said. “At times, he wore the uniform, then later seemed to express regret.”

Like other researchers, particularly those involved in large projects that bring together people with different skills and from various cultural backgrounds, Oppenheimer led a diverse team of scientists amid the heightened tension of World War II.

Oppenheimer was “shown to have been granted an extremely powerful position and was able to form a relatively diverse team, although he was not able to win over all the brightest minds,” Keister wrote.

Joshua-Tor suggested Oppenheimer “charmed” the other scientists, who were so driven by the science and the goal that they “accepted him. The leader of the team should be a great scientist, but doesn’t necessarily have to be the biggest genius. There is a genius in being able to herd the cats in the right way.”

Joel Hurowitz, Associate Professor in the Department of Geosciences at Stony Brook University, “loved” the movie. Hurowitz has worked with large projects with NASA teams as a part of his research effort.

Hurowitz suggested that the work that goes into coordinating these large projects is “huge” and it requires “a well laid out organizational structure, effective leadership, and a team that is happy working hard towards a common goal.”

‘Stunning’ first bomb test

Keister described the first nuclear bomb test as “stunning” in the movie. “I have to wonder how the environmental and health impacts of such a test came to be judged as inconsequential.”

Some local scientists would have appreciated and enjoyed the opportunity to see more of the science that led to the creation of the bomb.

Science is the “only place the movie fell short,” Hannun said. “They could have spent a bit more time to indicate the basic science behind the project and maybe a bit more about the scientific accomplishments of the various participants.”

Given the focus of the movie on Oppenheimer and his leadership and ultimate ambivalence about the creation of the atomic bomb, Keister suggested that scientists “could be better encouraged to understand the impacts of applied uses of new discoveries. Scientists can learn to broaden their view to include means of mitigating potential negative impacts.”

Research sponsors, including taxpayers and their representatives, have an “ethical responsibility to incorporate scientists’ views of the full impacts into their decisions regarding applications and deployment of new technology,” Keister said.

Joshua-Tor thinks there “always has to be an ongoing conversation between scientists and the citizenry” which has to be an “informed, somewhat dispassionate conversation.”

Recommended movies about scientists

Local researchers also shared some of their film recommendations about scientists.

Hurowitz wrote that his favorite these days is Arrival, a science fiction film starring Amy Adams. If Hurowitz is looking for more lighthearted fare, he writes that “you can’t go wrong with Ghostbusters,” although he’s not sure the main characters Egon, Ray and Peter could be called scientists.

Keister also enjoys science fiction, as it “often challenges us with ethical dilemmas which need to be addressed.” While he isn’t sure he has a favorite, he recommended the sci-fi thriller Ex Machina starring Alicia Vikander as a humanoid robot with artificial intelligence,.

Joshua-Tor recalls liking the film A Beautiful Mind starring Russell Crowe and Jennifer Connelly as John and Alicia Nash. She also loved the film Hidden Figures, starring Taraji P Henson, Octavia Spencer and Janelle Monáe.

John Moses. Photo courtesy of CSHL

By Daniel Dunaief

It sounds like something straight out of a superhero origin story.

With resistance to widely used drugs becoming increasingly prevalent among bacteria, researchers and doctors are searching for alternatives to stem the tide.

That’s where shape shifting molecules may help. Cold Spring Harbor Laboratory Professor of Organic and Click Chemistry John Moses and his team have attached the drug vancomycin to a molecule called bullvalene, whose atoms readily change position and configuration through a process called a thermal sigmatropic rearrangement as atoms of carbon break and reform with other carbon atoms.

The combination of the bullvalene and vancomycin proved more effective than vancomycin alone in wax moth larva infected with vancomycin resistant Enteroccoccus bacteria.

“Can I make a molecule that changes shape and will it affect bacteria? That was the question,” Moses said. The promising early answer was, yes!

Moses believes that when the bullvalene core is connected to other groups like vancomycin, the relative positions of the drug units change, which likely change properties related to binding.

The urgency for novel approaches such as this is high, as drug resistant bacteria and fungi infect about 2.8 million people in the United States per year, killing about 35,000 of them. 

In his own life, Moses said his father almost died from a bacterial infection five years ago. Vancomycin saved his father’s life, although the infection became resistant to the treatment. Other drugs, however, conquered the resistant strain.

“We need to work hard and develop new antibiotics, because, without them, there will be a lot more misery and suffering,” Moses explained.

To be sure, an approach like this that shows promise at this early stage with an insect may not make the long journey from a great idea to a new treatment, as problems such as dosage, off target effects, toxicity, and numerous other challenges might prevent such a treatment from becoming an effective remedy.

Still, Moses believes this approach, which involves the use of click chemistry to build molecules the way a child puts together LEGO blocks, can offer promising alternatives that researchers can develop and test out on a short time scale.

“We shouldn’t be restricted with one set of ideas,” Moses said. “We should keep testing hypotheses, whether they are crazy or whatever. We’ve got to find alternative pathways. We’re complementary” to the standard approach pharmaceutical companies and researchers take in drug discovery.

Looking to history, Moses explained that the founders of the Royal Society in 1660 followed the motto “nullius in verba,” or take nobody’s word for it. He believes that’s still good advice in the 21st century.

The shape shifting star

Moses has described this bullvalene as a Rubik’s Cube, with the parts moving around and confounding the bacteria and making the drug more effective.

The CSHL scientist and his team don’t know exactly why shape shifting makes the drug work in this moth model.

He speculated that the combination of two vancomycin units on either side of a bullvalene center is punching holes in the cell wall of the bacteria.

Moses is eager to try to build on these encouraging early developments. “If you can make it, then you can test it,” he said. “The sooner the better, in my opinion.”

Moses acknowledged that researchers down the road could evaluate how toxic this treatment might be for humans. It didn’t appear toxic for the wax moth larvae.

Welcoming back a familiar face

Adam Moorhouse
Photo by Rebecca Koelln

In other developments in his lab, Moses recently welcomed Adam Moorhouse back to his team. Moorhouse, who serves as Chemistry Data Analyst, conducted his PhD research in Moses’s lab at the University of Oxford.

Moorhouse graduated in 2008 and went on to work in numerous fields, including as an editor for the pharmaceuticals business and for his own sales consultancy. In 2020, he had a motorcycle accident (which he said was his fault) in which he broke 16 bones and was hospitalized for a while. During his recovery, he couldn’t walk.

At the time, he was working in the intense world of sales. After the accident, Moorhouse decided to build off his volunteer work with disabled children and become a high school teacher. After about 18 months of teaching, Moorhouse reconnected with Moses.

“It’s nice getting here and thinking about chemistry and thinking about ideas and communicating those ideas,” Moorhouse said.

He has hit the ground running, contributing to grants and helping to translate intellectual property into commercial ventures.

The chance to work on projects that get molecules into humans in the clinic was “really exciting,” Moorhouse said. “I’m back to try and support that.”

Moorhouse will be working to procure funding and to build out the business side of Moses’s research efforts.

“Where I’d like to lend a hand is in driving ongoing business discussions,” Moorhouse said. He wants to “get these small molecules into the clinic so we can see if they can actually treat disease in humans.” The vehicle for that effort eventually could involve creating a commercial enterprise.

Like Moses, Moorhouse is inspired and encouraged by the opportunity for small operations like the lab to complement big pharmaceutical companies in the search for treatments.

Moses believes the work his lab has conducted has reached the stage where it’s fundable. “We’ve done something that says, ‘we checked the box,’” he said. “Let’s find out more.”

Currently living on campus at CSHL, Moorhouse appreciates the opportunity to do some bird watching on Long Island, where some of his favorites include woodpeckers, herons, egrets, robins and mockingbirds.

He is tempted to get back on a motorcycle and to return to mountain biking.

As for his work, Moorhouse is excited to be a part of Moses’s lab.

“Back in my PhD days, [Moses] was always an idea machine,” Moorhouse said. “The aim is to move ideas to the clinic.”


A statue of Charles Darwin (and finch) created by sculptor Pablo Eduardo overlooks the harbor on the campus of Cold Spring Harbor Laboratory. Photo courtesy of CSHL

By Tara Mae

Scientific study is a perpetual testimony to the feats and foibles of human nature, intricately intertwined in ways that continue to be excavated by inquiring minds bold enough to imagine. 

Cold Spring Harbor Laboratory (CSHL), which has largely been a titan in such innovative investigations, will offer a series of walking tours on select weekends from Saturday, May 20, through Sunday, August 27, starting at 10 a.m. The hour and a half long tours will traverse the past, present, and future of the complex and its work therein. 

“We are most excited to get people to the Laboratory who have always wondered what goes on here. So many have heard about us, driven by us, read about us, but they have never dug deeper. This walking tour is the chance to learn who we are,” said Caroline Cosgrove, CSHL’s Community Engagement Manager.

Conducted by trained tour guides, including Cold Spring Harbor Laboratory graduate students and postdoctoral fellows, the walks strive to bridge the gap between the physical realm and scientific theory. 

“These tours encompass the stunning grounds, the Lab’s history, and our current facilities and work. Community members, whether they have a background and interest in science, can come and learn from current graduate students about the world-renowned work going on in their very backyard,” explained Cosgrove. 

Probing CSHL’s ongoing research and program development for plant and quantitative biology, cancer, and neuroscience, the tours will encompass details about its historic and modern architecture, Nobel legacy, and identity evolution. Additionally, these scenic, scholarly strolls explore the practices and procedures of CSHL, with behind-the-scenes sneak peaks into the inner workings of scientific investigation. 

“As long as the tour guide’s laboratory is open and available, folks get a walk through and see the student’s own lab station,” Cosgrove said. “Whether it’s a cancer research lab, a neuroscience lab, a plant research lab, you get to see where all the magic happens.” 

Established in 1890, CSHL’s North Shore campus is a beacon of biology education, with 52 laboratories and more than 1100 staff from more than 60 countries. Eight scientists associated with CSHL have earned a Nobel Prize in physiology or medicine. This internationally recognized center of scientific research is also a local history and education site, where students of all ages and backgrounds come to study. 

“History has been, and will continue to be, made here. Please come get to know us,” said Cosgrove. 

Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor offers walking tours on May 20 and 21, June 24 and 25, July 29 and 30 and Aug. 26 and 27 at 10 a.m. Tours begin in the lobby of the Grace Auditorium. Tickets are $5 per person. To order, visit For more information, call 516-367-8800.

Lucas Cheadle with two pieces of artwork in his office, from left by Porferio Tirador 'Gopher' Armstrong, a Cheyenne-Caddo native from Oklahoma and Oklahoma Kiowa artist Robert Redbird. Photo by Austin Ferro

By Daniel Dunaief

Cold Spring Harbor Laboratory Assistant Professor Lucas Cheadle knows a thing or two about under represented groups in the field of Science, Technology, Engineering and Mathematics.

Of Chickasaw, Choctaw and Cherokee lineage, Cheadle, who was born in Ada, Oklahoma, was recently named one of 31 inaugural Howard Hughes Medical Institute’s (HHMI) Freeman Hrabowski scholars.

Lucas Cheadle. Photo by Steve Ryan/ AP Images for HHMI

The first scholars in this highly competitive and unique program, which drew 1,036 applicants, will receive funding that will last at least five years and could get as much as $8.6 million each for their promising early research and for supporting diversity, equity and inclusion in their labs.

“This is the first time a program of this type and magnitude has been attempted,” said HHMI Vice President and Chief Scientific Officer Leslie Vosshall. The scholars are “doing things that set them in the top one percent in creativity and boldness and we are certain we are going to have really healthy, inclusive, diverse labs.”

Vosshall said the scholars, which include scientists from 22 institutions, including Columbia, Harvard, Duke, Cornell, Princeton, the University of Pennsylvania, and Massachusetts Institute of Technology, hit it “out of the park” in their science and diversity efforts.

HHMI, which has committed $1.5 billion for Freeman Hrabowski Scholars, will award about 30 of these select scholarships every other year for the next 10 years, supporting promising scientists who can serve as mentors for under represented groups while also creating a network of researchers who can provide advice and collaborations.

The first group of scientists to receive this support is “diverse in such a way that it reflects the U.S. population,” Vosshall said.

The program is named after Freeman Hrabowski, who was born in Birmingham, Alabama and was president of the University of Maryland, Baltimore County, from 1992 to 2022. Hrabowski, who was arrested during the civil rights movement, created a tutoring center in math and science for African Americans in high school and college and helped create the Meyerhoff Scholars Program.

Cheadle was celebrating the December holidays in Oklahoma when he learned he was a semifinalist, which was “really surprising and exciting,” he recalled. Becoming an HHMI scholar is “amazing” and “very validating,” he said.

Bruce Stillman, President and CEO of CSHL, suggested that HHMI recognition is “a prestigious achievement” and, in a email, wrote that he was “pleased that [Cheadle] was included in the list of remarkable scientists.”

Stillman predicted that Cheadle’s passion about increasing diversity in science would have a “major influence” on CSHL.”

Scientific questions

Cheadle appreciates how HHMI funds the scientist, not individual projects. With this unrestricted funding, which includes full salary and benefits and a research budget of about $2 million over the first five years and eligibility to participate in HHMI capital equipment purchasing programs, Cheadle and other scholars can pursue higher-risk, higher-reward projects.

“If I have a crazy idea tomorrow, I can do that with this with funding,” Cheadle explained.

Cheadle, who joined CSHL in August of 2020, studies the way the immune system shapes brain development, plasticity and function. He also seeks to understand how inflammatory signals that disrupt neural circuit maturation affect various disorders, such as autism.

Last September, Cheadle and his lab, which currently includes six postdoctoral researchers, two PhD students, one master’s student, a lab manager and two technicians, published a paper in Nature Neuroscience that showed how oligodendrocyte precursor cells, or OPCs, help shape the brain during early development.

Previously, scientists believed OPCs produced cells that surrounded and supported neurons. Cheadle’s recent work shows that they can play other roles in the brain as well, which are also likely instrumental in neural circuit construction and function.

When young mice raised in the dark received their first exposure to light, these OPCs engulfed visual processing circuits in the brain, which suggested that they helped regulated connections associated with experience.

With this new position and funding, Cheadle also plans to explore the interaction between the development of nerves in the periphery of the brain and different organs in the body, as well as how immune cells sculpt nerve connectivity.

He is not only studying this development for normal, healthy mice, but is also exploring how these interactions could explain why inflammation has arisen as such an important player in neurodevelopmental dysfunction.

Stillman explained that Cheadle’s work will “have broad implications.”

A talented, balanced team

Cheadle is committed to creating a balanced team of researchers from a variety of backgrounds.

“As principal investigators,” Cheadle said, “we have to actively work to have a diverse lab.”

He has posted advertisements on women’s college forums to garner more applications from women and under represented groups. He has also adopted a mentorship philosophy that focuses on inclusivity. 

Cheadle explained that he hopes to be adaptable to the way other people work. Through weekly lab meetings, mentorship arrangements and reciprocal interactions, he hopes to provide common ground for each aspiring scientist.

He recognizes that such goals take extra effort, but he feels the benefits outweigh the costs.

During annual events, Cheadle also leans in to the cultural diversity and differences of his staff. He hosts a pre-Thanksgiving pot luck dinner, where everybody brings a food item that’s important and close to them. 

Last year, he made pashofa out of cracked corn that his stepmom sent him from the Chickasaw Nation in Oklahoma. Pashofa is a traditional meat and corn Chickasaw dish. Other lab members brought tropical beverages common in Brazil.

In terms of diversity in science, Cheadle believes such efforts take years to establish. Through an approach that encourages people from different backgrounds to succeed in his lab, Cheadle hopes to share his thoughts and experiences with other researchers.

Cheadle last summer hosted a Chickasaw student on campus to do research. He is working with the Chickasaw Nation to expand that relationship.

As for the Freeman Hrabowski scholars, Vosshall said all HHMI wants to do is “allow everybody to do science.-


HHMI Chief Scientific Officer Vosshall celebrates benefits of diversity in science

By Daniel Dunaief

It’s not one or the other. She believes in both at the same time. For Leslie Vosshall, Vice President and Chief Scientific Officer at Howard Hughes Medical Institute, science and diversity are stronger when research goals and equity work together.

Leslie Vosshall. Photo by Frank Veronsky

That’s the mission of the new and unique HHMI Freeman Hrabowski Scholars program. HHMI this week named 31 inaugural scholars as a part of an effort designed to support promising scientists who provide opportunities to mentor historically under represented groups in research.

Cold Spring Harbor Laboratory Assistant Professor Lucas Cheadle was among the 31 scientists who became HHMI scholars (see related story above), enabling him to receive financial support for the next five years and up to $8.6 million for the next decade.

In an interview, Vosshall said the “special sauce of this group” of scientists who distinguished themselves from among the 1,036 who applied was that they excel as researchers and as supporters of diversity. Bringing in people who may not have had opportunities as scientific researchers not only helps their careers but also enables researchers to take creative approaches to research questions.

“When you bring in people from the ‘out group’ who have been historically excluded, they have an energy of getting into the playing field,” she said. That innovation can translate into successful risk taking.

As an example, Vosshall cited Carolyn Bertozzi, a chemist at Stanford University who shared the 2022 Nobel Prize in Chemistry for helping to develop the field of bioorthogonal chemistry, which involves a set of reactions in which scientists study molecules and their interactions in living things without interfering with natural processes.

Her lab developed the methods in the late 1990’s to answer questions about the role of sugars in biology, to solve practical problems and to develop better tests for infectious diseases. “This scrappy band of women chemists tried this crazy stuff” which provided “massive innovations in chemical biology,” Vosshall said. Mainstream science often solidifies into a groove in which the same thing happens repeatedly. “Innovation comes from the edges,” she added.

In her own to hire staff in her lab, Vosshall has taken an active approach to find candidates from under served communities. “People who have pulled themselves up have worked so hard to get to where they are,” she said. “It’s important to dig deeper to find talent everywhere.”

Keeping away from the off-ramp

The number of under represented groups in science has improved over the last few decades. Indeed, when Vosshall joined Rockefeller University, where she is the Robin Chemers Neustein Professor, she couldn’t count 10 women faculty. Now, 23 years later, that number has doubled.

The number of people in under represented groups in graduate programs has increased. The problem, Vosshall said, is that they “take the off-ramp” from academic science” because they don’t always feel “welcome in the labs.” Supporting diversity will keep people in academic science, who can and will make important discoveries in basic and translational science.

As a part of the Freeman Hrabowski program, HHMI plans to survey people who were trainees in these labs to ask about their mentoring experience. By tracking how developing scientists are doing, HHMI hopes to create a blueprint for building diversity.

HHMI has hired a consultant who will analyze the data, comparing the results for the results and career trajectories. The research institute will publish a paper on the outcome of the first cohort. Researchers in this first group will not only receive money, but will also have an opportunity to interact with each other to share ideas.

New approach

When Vosshall earned her PhD, she considered an alternative career. She bought a training book for the Legal Scholastic Aptitude Test and considered applying to law school, as she was “fed up with how I was treated and fed up with science”

Nonetheless, Vosshall, who built a successful scientific career in which she conducts research into olfactory cues disease-bearing insects like mosquitoes seek when searching for humans, remained in the field.

To be sure, Vosshall and HHMI aren’t advocating for principal investigators to hire only people from under represented groups. The promising part of this scholarship is that HHMI found it difficult to get the final number down to 31, which “makes me optimistic that the [scientific and mentorship] talent is out there,” she said. Over the next decade, HHMI plans to name about 30 Freeman Hrabowski scholars every other year. If each lab provides research opportunities across different levels, this will help create a more diverse workforce in science, which, she said, benefits both prospective researchers and science.


Kyle Swentowsky in front of the maize fields at CSHL’s Upland Farm preserve. Photo courtesy of CSHL

By Daniel Dunaief

Farmers typically plant the sweet corn that fills Long Islander’s table some time between late April and June, with flavorful yellow kernels ready to eat about eight weeks later.

But what if corn, which is planted and harvested on a typical annual crop schedule, were perennial? What if farmers could plant a type of corn that might have deeper roots, would become dormant in the winter and then grew back the next year?

Kyle Swentowsky, holding corn on the north fork of Long Island.

Cold Spring Harbor Laboratory postdoctoral researcher Kyle Swentowsky, working in the lab of  Professor Dave Jackson, is interested in the genetics of perennial grasses, which includes maize, wheat, rice, barley, sorghum and others. He uses maize as a model.

Extending the work he did as part of his PhD research at the University of Georgia, Swentowsky, who arrived at CSHL in July of 2021, is searching for the genes that cause the major differences between annual and perennial grasses.

Kelly Dawe, who was Swentowsky’s PhD advisor, described him as “passionate” “diligent” and “thoughtful.” Dawe explained that perennials have been beneficial in the farming of other crops. Perennial rice has enabled farmers to save 58.1 percent on labor costs and 49.2 percent on input costs with each regrowth cycle, Dawe explained, adding, “The rice work is much farther along, but could have a similar impact on corn.”

Aside from producing crops over several years without requiring replanting, perennial corn also has several other advantages. Perennials, which have deeper roots, can grow in soil conditions that might not be favorable for annual crops, which can help stabilize the soil and expand the range of farmable land.

Recently, people have also considered how scientists or farmers might take some of the sub-properties of perennials and apply them to annual crops without converting them to perennials. Some annuals with perennial traits might stay green for longer, which means they could continue the process of photosynthesis well after annuals typically stop.

A complex challenge

Scientists have been trying to make perennial corn for about 50 years. The perennial process is not as simple as other plant traits.

“We don’t understand all the underlying sub properties of being perennial,” Swentowsky said. “It’s very complicated and involves a lot of regions in the genome. My work aims to get at some of these sub traits and genomic loci that are involved in this process.”

In his work, Swentowsky is interested in the sub traits that the major genes control. He expects that a reliable perennial corn wouldn’t make the annual variety obsolete. Even after researchers develop an effective perennial corn, farmers may still cultivate it as an annual in some environments.

In the bigger picture, Swentowsky, like other plant researchers at CSHL and elsewhere around the world, recognizes the challenge of feeding a population that will continue to increase while climate change threatens the amount of arable land.

Plant breeders need to continue to come up with ways to increase crop yield to boost food production, he suggested. While some people have considered dedicating resources to back up plans like astro-botany — or growing crops in space — Swentowsky suggested this was challenging and urged ongoing efforts to produce more food on Earth.

Impressed with the way Matt Damon’s character in the movie The Martian farms potatoes on the Red Planet, Swentowsky suggested that such an agricultural effort would be challenging on a large scale in part because of the extreme temperature variations.

As for work on Earth, perennial corn may also remove more carbon dioxide from the air, reducing the presence of greenhouse gases such as carbon dioxide.

Swentowsky cautioned that the idea of carbon farming is still relatively new and researchers don’t know what would make a good carbon farming plant yet. At this point, his work has involved breeding and back crossing corn plants. Once he develops a better idea of what genes are involved in the perennial life cycle, he will consider taking a trans-genetic approach or use the gene editing tool Crispr to test the effects of the involved genes.

Swentowsky expects that several genetic changes may be necessary to develop a perennial plant. He and others have mapped the master regulators of perenniality to three major genes. He believes it’s likely that dozens or even hundreds of other genes scattered throughout the genome play a small role influencing perennial sub-traits.

California roots

A current resident of Long Beach, Swentowsky grew up in Sacramento, California. He earned his undergraduate and master’s degrees at the University of California at Santa Barbara. After six years, he was “tired of perfect weather,” he laughed. He would sweat through football games in January, when it was 80 degrees amid a cloudless sky.

As an undergraduate, he took a plant development course and appreciated the elegant way scientists tested plants. His two favorite scientists are Gregor Mendel, whose pioneering pea work led to the field of modern genetics, and Barbara McClintock, a former CSHL scientist whose Nobel Prize winning research on corn led to an understanding of transposable elements, or jumping genes in which genes change position on a chromosome. 

Outside of the lab, Swentowsky enjoys traveling, including camping and backpacking, spending time on the beach, attending reggae, alternative, classic rock, hip hop and electric concerts and going to breweries. During the winter, his favorite beers are stout and porter. In warmer weather, he imbibes sour IPA.

Swentowsky doesn’t just study corn: he also enjoys eating it. One of his favorites is elote, or Mexican street corn. He grills the corn on a barbecue, covers it with mayonnaise and cotija cheese and sprinkles lyme or chili powder on it.

Swentowsky, who is funded through the summer of 2025 at CSHL, appreciates the opportunity to contribute to work that could support future farming efforts. He hopes that studying perenniality in corn could have future applications.

CSHL Associate Professor Stephen Shea and Postdoc Yunyao Xie in Shea’s lab. Photo from CSHL/2020

By Daniel Dunaief

Good parenting, at least in mice, is its own reward.

No, mice don’t send their offspring to charter schools, drive them to endless soccer and band practices or provide encouragement during periods of extreme self doubt.

What these rodents do, however, protects their young from danger.

When a young mouse wanders, rolls or strays from the nest, it becomes distressed, calling out mostly to its mother, who is the more effective parent, to bring it back to safety.

Responding to these calls, the mother mouse carries the young back to the safety of the nest.

This behavior involves a reward system in a region of the mouse brain called the ventral tegmental area, or VTA. When the mouse effectively retrieves its young, the VTA releases the neurotransmitter dopamine, which is the brain’s way of saying “well done!”

In a paper published in December in the journal Neuron, Cold Spring Harbor Laboratory Associate Professor Stephen Shea and his postdoctoral researcher Yunyao Xie, who worked in the lab from 2019 to 2021, likened the release of dopamine in this area to a neurological reward for engaging in the kind of behavior that protects their young.

The research “proposes a mechanism that shapes behavior in accordance with that reward,” Shea said. The connection between dopamine in a reward system is an established paradigm.

“There was plenty of smoke there,” he said. “We didn’t pull this out of thin air.”

Indeed, in humans, mothers with postpartum depression have disrupted maternal mood, motivation and caregiving. PPD is linked to dysfunction of the mesolimbic dopamine system, which is a neural circuit that involves the VTA, Xie explained.

“Studies using functional magnetic resonance imaging (fMRI) revealed that the reward brain areas including VTA in healthy mothers have higher response to their own babies’ smiling faces than those in mothers with PPD,” Xie added.

What’s new in this research, however, is that it is “a study of how these signals use mechanisms to shape behavior and social interaction,” Shea said.

How the process works

The feedback loop between dopamine in the VTA and behavior involves a cumulative combination of dopamine interactions.

Dopamine is not at its highest level when the mouse mom is engaging in effective pup retrieval.

“Dopamine is shaping future, not current behavior,” Shea said. “If dopamine was driving the mouse on a current trial, a high dopamine level would be associated with high performance. The trial found the opposite: a low dopamine level was associated with high performance in a given trial, and vice versa.”

Like a skater laying her blades down effortlessly and gracefully across the ice after spending hours exerting energy practicing, the mother mouse engaged in the kind of reinforcement learning that required less dopamine to lead to effective pup saving behavior.

As the performance increases, dopamine diminishes over time, as the reward is “more expected,” reflecting a nuanced dynamic, Shea said.

To test the correlation between dopamine levels in the VTA and behavior, Shea and Xie created an enclosure with two chambers. They put a naive virgin female mouse, which they called surrogates, on one side and played specific sounds behind a door on each side of the chamber. The test mice initially had “no experience in maternal behaviors,” Xie explained.

As these surrogates became more experienced by either observing mothers or practicing on their own, the amplitude of the VTA dopamine signals got smaller.

To provide a control for this experiment, Xie monitored a group of naive virgin female mice who spent less time with pups and had to figure out how to retrieve them on their own under similar neurological monitoring conditions. The dopamine signals in this group stayed elevated over days and their performance in maternal behaviors remained poor.

Through these experiments, Xie and Shea concluded that “there is a negative correlation between the dopamine signals in the VTA and their performance in maternal behaviors,” explained Xie.

‘Mind blowing’ moment

In her experiments, Xie used optogenetic tools that allowed her to inhibit the activity of dopaminergic neurons in the VTA with high temporal precision.

Shea appreciated Xie’s hard work and dedication and suggested the discoveries represent a “lot of her creativity and innovation,” he said.

A native of China, Xie said her grandparents used to have a garden in which they taught her the names and morphologies of different plants during her childhood. She enjoyed drawing these plants.

In graduate school, she became more interested in neuroscience. She recalls how “mind-blowing” it was when she learned about the work by 1963 Nobel laureates Alan Hodgkin, Sir Andrew Fielding Huxley and John Eccles, who established a mathematical model to describe how action potentials in neurons are initiated and propagated.

In the study Xie did with Shea, she found that the dopamine signals in the VTA encoded reward prediction errors in maternal behaviors that was consistent with the mathematical model.

In the bigger picture, Xie is interested in how neural circuits shape behaviors. The neural circuits of most natural behaviors, such as defensive behaviors and maternal behaviors are hard-wired, she added.

Mice can also acquire those behaviors through learning. She is interested in how pup cues are perceived as rewards and subsequently facilitate learning maternal behavior. She found a great fit with Shea’s lab, which focuses on the neural mechanism of maternal behavior.

Xie enjoyed her time at Cold Spring Harbor Laboratory, where she could discuss science with colleagues by the bench, at the dining room or at one of the many on site seminars. She also appreciated the opportunity to attend neuroscience seminars with speakers from other schools, which helped expand her horizons and inspire ideas for research.

Next steps

As for the next steps, Shea said he believes there is considerable additional follow up research that could build on these findings. He would like to apply methods that measure the activity in individual neurons. Additionally, with a number of targets for dopamine, he wants to figure out what areas the neurotransmitter reaches and how the signals are used when they get there. More broadly, he suggested that the implications for this research extend to human diseases. 

From left, Alea Mills and Xueqin Sun Photo from CSHL

By Daniel Dunaief

People have natural defenses against cancer. Proteins like P53 search for unwelcome and unhealthy developments. 

Sometimes, mutations in P53, which is known as the “guardian of the genome,” rob the protein of its tumor fighting ability. In more than seven out of ten cases, the brain tumor glioblastoma, which has a grim prognosis for people who develop it, has an intact P53 protein.

So what happened to P53 and why isn’t it performing its task?

That’s what Cold Spring Harbor Laboratory Professor and Cancer Center member Alea Mills and postdoctoral researcher Xueqin “Sherine” Sun wanted to know.

Starting with the idea that something epigenetic was somehow blocking P53, Sun conducted numerous detailed experiments with the gene editing tool CRISPR-Cas9.

She knocked out parts of the chromatin regulating machinery, which determines whether factors for DNA replication, gene expression, and the repair of DNA damage can access genes and perform their tasks.

The researchers wanted to find “something specific to glioblastoma,” Mills said in an interview. Working with a team of researchers in Mills’s lab, Sun focused on the protein BRD8.

In experiments with mice, Sun and her colleague inhibited this specific protein by destroying the gene that encodes it. That step was enough to stop the tumor from growing and allowed the mouse to live longer.

Mills and Sun published their work in the prestigious journal Nature just before the holidays.

The article generated considerable buzz in the scientific community, where it was in the 99th percentile among those published at the same time in attracting attention and downloads. It also attracted attention on social media platforms like Twitter and LinkedIn.

“We see this as a major discovery, and are not surprised that many others think that the impact is extraordinary,” Mills said. The paper “has the potential of having a significant impact in the future. The work is completely novel.”

While finding a connection between BRD8 and glioblastoma suggests a target for researchers to consider in their search for new glioblastoma treatments, a potential new approach for patients could be a long way off.

“We cannot predict how long it will take to be able to help patients” who have glioblastoma, Mills said.

A promising step

From left, Alea Mills and Xueqin Sun Photo from CSHL

Still, this finding provides a promising step by showing how knocking out the BRD8 protein can enable P53 to gain access to a life threatening tumor.

Sun and Mills said BRD8 and its partners lock down genes that are normally turned on by P53.

“What you inherit from mom and dad is one thing,” said Mills. “How it’s packaged, the epigenetic mechanism that keeps it wrapped up or open, is key in how it’s all carried out within your body.”

By targeting BRD8, Mills and her team opened the chromatin, so P53 could bind and turn on other cancer fighting genes.

After receiving patient samples from Northwell Health, Stanford and the Mayo Clinic, the team studied tissue samples from patients battling glioblastoma. Those patients, they found, had higher concentrations of BRD8 than people without brain cancer.

Researchers and, down the road, pharmaceutical companies and doctors, are careful to make sure removing or reducing the concentration of any protein doesn’t have so-called “off target effects,” which would interfere with normal, healthy processes in cells.

Mills said they tested such actions in the context of neural stem cells in the brain. At this point, removing BRD8 didn’t have any “deleterious consequence,” she said. 

Her lab is working to see the effect of reducing or removing the mouse version, also called Brd8, during development by engineering mice that lack this protein.

Future research

An important next step in this research involves searching for and developing viable inhibitors of the BRD8 protein.

For histone readers like BRD8, researchers look for an active domain within the protein. The goal is to interrupt the interface in their interactions with histones.

In creating molecules that can block the action of a protein, researchers often start with the structure of the protein or, more specifically, the active site.

Sun, who is currently applying for jobs to run her own lab after working at Cold Spring Harbor Laboratory for over eight years, is hoping to purify enough of the protein and determine its structure.

Sun is working on x-ray crystallography, in which she purifies the protein, crystallizes it and then uses x-rays to determine the atomic structure.

Sun described the search for the structure of the protein as an “important direction” in the research. “Once we solve the structure” researchers can focus on drug design, testing and other experiments.

She suggested that the search for a small molecule or compound that might prove effective in inhibiting BRD8 would involve optimizing efficiency and activity.

There is a “long way to go” in that search, Sun added.

She is working to generate a chemical compound in collaboration with other groups.

A long, productive journey

Born and raised in China, Sun has been an active and important contributor to Mills’s lab.

“I’ll miss [Sun] personally as well as in the lab,” Mills said. “She’s been a really good role model and teacher across the Cold Spring Harbor campus and in my lab.”

Mills is “really excited about [Sun’s] future,” she said. “She’ll be really great” at running her own lab.”

For her part, Sun enjoyed her time on Long Island, where she appreciated the natural environment and the supportive culture at Cold Spring Harbor Laboratory.

Sun described her time on Long Island as a “very exciting and satisfying journey.” 

She is determined to study and understand cancer for a number of reasons.

“I know people who died of cancer,” she said. “It’s a terrible disease and it’s urgent to find more efficient therapeutic strategies to stop cancers and improve human heath.”

Sun is also eager to embrace the opportunity to mentor and inspire other students of science.

“Teaching is very important,” she said. She looks forward to helping students grow as professionals to create the “next generation of scientists.”

CSHL’s David Spector (center) and postdoctoral fellows Rasmani Hazra on left and Gayan Balasooriya on right. Photo courtesy of CSHL

By Daniel Dunaief

One came from India, the other from Sri Lanka. After they each earned their PhD’s, they arrived on Long Island within seven months of each other about seven years ago, joining a lab dedicated to studying and understanding cancer. Each of them, working on separate projects, made discoveries that may aid in the battle against heart disease.

Working for principal investigator David Spector at Cold Spring Harbor Laboratory, postdoctoral fellow Rasmani Hazra, who grew up in Burdwan, India, found a link between a gene that affects cancer in mice that also can lead to a problem with the development of heart valves.

Hazra worked with two long noncoding RNAs that are highly expressed in mouse embryonic stem cells, which have the ability to differentiate into many different types of cells.

Specifically, she found that mice that didn’t have Platr4 developed heart-related problems, particularly with their valves.

At the same time, postdoctoral fellow Gayan Balasooriya, who was born and raised in Sri Lanka, discovered that a single, non-sex gene is governed by different epigenetic mechanisms based on whether the gene is inherited from the mom or the dad.

While it was known that males are more susceptible to heart disease than females, researchers did not know which copy of the gene related to those diseases are expressed. This discovery could help in understanding the development of heart defects.

“Although we ended up at heart development” in both of these published studies, “we didn’t initiate” looking for heart-related information, said Spector. “The science led us there.

Spector, however, expects that the lessons learned about differentiation in the context of the developing heart can also “impact out knowledge about tumors” which he hopes will eventually lead to advances in how to treat them.

He added that any clinical benefit from this work would take additional research and time.

An on and off switch

In Hazra’s study, which was published in the journal Developmental Cell, she worked with Platr4 because humans have several possible orthologous genes. 

When Platr4 expression, which shuts down after birth, is deleted from cells or embryos, the mice died from heart valve problems.

The human equivalent of Platr4 is located on chromosome 4. At this point, clinical case studies have connected the deletion of this chromosome to cardiac defects in humans.

Hazra said her project initially examined the function of these long non-coding sections of RNA. She was exploring how they affected differentiation. She found this link through in vitro studies and then confirmed the connection in live mice.

Spector explained that this work involved extensive collaborations with other researchers at Cold Spring Harbor Laboratory, including teaming up with researchers who can do electrocardiograms on mice and who can assess blood flow.

A shared mouse imaging resource also helped advance this research.

“One of the advantages of Cold Spring Harbor Laboratory is that we have over 10 shared resources, each of which specializes in sophisticated technologies that scientists can use on their own projects,” he said. Each lab doesn’t have to learn and develop its own version of these skills.

Hazra plans to continue to study other long noncoding RNA. She is also working on glioblastoma, which is a form of brain cancer.

Hazra plans to start her own lab next fall, when she completes her postdoctoral research.

Inactive gene

Balasooriya, meanwhile, published his research in the journal Nature Communications.

He used RNA sequencing to identify numerous genes. He also looked at whether the RNAs originated from the mom or dad’s genes in individual cells.

Also planning to start his own lab next fall, Balasooriya found changes that alter gene expression between the alleles from the mother and the father experimentally and through data mining approaches.

“What was most surprising in my studies is that [he identified] the gene from the father’s side and the mother’s side are regulated in a different manner,” Balasooriya said. “I’m interested in following up on that finding.”

The next step for him is to look not only at the heart, but, more broadly, at how monoallelic gene expression changes the way regulators affect development and disease.

“I want to do a deep dive to find out the mechanisms” involved in this expression of a single copy of the gene, Balasooriya said, which could provide ways to understand how to control the process.

In the long run, this kind of research could provide insights into ways to treat heart disease as well as other diseases like cancer and immune diseases.

Growing up in the North Western Province in Sri Lanka, Balasooriya was interested in math and science. After he finished his bachelor’s degree in biology in Sri Lanka, he earned a master’s in molecular biology at the University of Hertfordshire in England. He “got so excited about biology and exploring new fields” that he decided to pursue his PhD at the University of Cambridge, England.

After college, he worked in computer science for a while and realized he was not passionate about it, which encouraged him to do his master’s. The experience in computer science helped him with bioinformatics.

As for Spector, he is pleased with the work of both of his postdoctoral researchers. “This is what being a principal investigator is all about, having young people join your lab, sitting down with them, discussing a potential project, not really knowing where it’s going to go,” he said.

He described both members of his team as “extremely successful” who were able to make discoveries that they shared in prestigious journals. Balasooriya and Hazra both laid the groundwork to go and start their own careers. 

“Seeing the fruits of their work is the most rewarding experience” as the leader of a lab, Spector said.