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Cold Spring Harbor Laboratory

Jose M. Adrover and Mikala Egeblad. Photo by Lijuan Sun

By Daniel Dunaief

Cold Spring Harbor Laboratory Professor Mikala Egeblad thought she saw something familiar at the beginning of the pandemic.

Mikala Egeblad. Photo from CSHL

Egeblad has focused on the way the immune system’s defenses can exacerbate cancer and other diseases. Specifically, she studies the way a type of white blood cell produces an abundance of neutrophil extracellular traps or NETs that can break down diseased and healthy cells indiscriminately. She thought potentially high concentrations of these NETs could have been playing a role in the worst cases of COVID.

“We got the idea that NETs were involved in COVID-19 from the early reports from China and Italy” that described how the sickest patients had severe lung damage, clotting events and damage to their kidneys, which was what she’d expect from overactive NETs, Egeblad explained in an email.

Recently, she, her post doctoral researcher Jose M. Adrover and collaborators at Weill Cornell Medical College and the Icahn School of Medicine at Mt. Sinai proved that this hypothesis had merit. They showed in hamsters infected with COVID and in mice with acute lung injuries that disabling these NETs improved the health of these rodents, which strongly suggested that NETs are playing a role in COVID-19.

“It was very exciting to go from forming a hypothesis to showing it was correct in the context of a complete new disease and within a relatively short time period,” Egeblad wrote.

Egeblad, Andover and their collaborators recently published their work in the Journal of Clinical Investigation Insight.

Importantly, reducing the NETs did not alter how much virus was in the lungs of the hamsters, which suggests that reducing NETs didn’t weaken the immune system’s response to the virus.

Additional experiments would be necessary to prove this is true for people battling the worst symptoms of COVID-19, Egeblad added.

While the research is in the early stages, it advances the understanding of the importance of NETs and offers a potential approach to treating COVID-19.

An unexpected direction

Jose Adrover. Photo from CSHL

When Adrover arrived from Spain, where he had earned his PhD from the Universidad Complutense de Madrid and had conducted research as a post doctoral fellow at the Spanish Center for Cardiovascular Research in March of 2020, he expected to do immune-related cancer research.

Within weeks, however, the world changed. Like other researchers at CSHL and around the world, Egeblad and Adrover redirected their efforts towards combating COVID.

Egeblad and Andover “were thinking about the virus and what was going on and we thought about trying to do something,” Adrover said. 

Egeblad and Adrover weren’t trying to fight the virus but rather the danger from overactive NETs in the immune system.

Finding an approved drug

Even though they were searching for a way to calm an immune system responding to a new threat, Egeblad and Adrover hoped to find a drug that was already approved.

After all, the process of developing a drug, testing its safety, and getting Food and Drug Administration approval is costly and time-consuming. 

That’s where Juliane Daßler-Plenker, also a postdoctoral fellow in Egeblad’s lab, came in. Daßler-Plenker conducted a literature search and found disulfiram, a drug approved in the 1950’s to treat alcohol use disorder. Specifically, she found a preprint reporting that disulfuram can target a key molecule in macrophages, which are another immune cell. Since the researchers knew this was important for the formation of NETs, Daßler-Plenker proposed that the lab test it.

Working with Weill Cornell Medical College and the Icahn School of Medicine at Mt. Sinai, Adrover explored the effect of disulfiram, among several other possible treatments, on NET production.

Using purified neutrophils from mice and from humans, Adrover discovered that disulfiram was the most effective treatment to block the formation of NETs.

He, Assistant Professor Robert Schwartz’s staff at Weill Cornell and Professor Benjamin tenOever at Mt. Sinai tried disulfiram on hamsters infected with SARS-Cov-2. The drug blocked net production and reduced lung injury.

The two experiments were “useful in my opinion as it strengthens our results, since we blocked NETs and injury in two independent models, one of infection and the other of sterile injury,” Adrover said. “Disulfuram worked in both models.”

More work needed

While encouraged by the results, Egeblad cautioned that this work started before the availability of vaccines. The lab is currently investigating how neutrophils in vaccinated people respond to COVID-19.

Still, this research offered potential promise for additional work on NETs with some COVID patients and with people whose battles with other diseases could involve some of the same immune-triggered damage.

“Beyond COVID, we are thinking about whether it would be possible to use disulfiram for acute respiratory distress syndrome,” Egeblad said. She thinks the research community has focused more attention on NETs.

“A lot more clinicians are aware of NETs and NETs’ role in diseases, COVID-19 and beyond,” she said. Researchers have developed an “appreciation that they are an important part of the immune response and inflammatory response.”

While researchers currently have methods to test the concentration of NETs in the blood, these tests are not standardized yet for routine clinical use. Egeblad is “sensing that there is more interest in figuring out how and when to target NETs” among companies hoping to discover treatments for COVID and other diseases.

The CSHL researcher said the initial race to gather information has proven that NETs are a potentially important target. Down the road, additional research will address a wide range of questions, including what causes some patients to develop different levels of NETs in response to infections.

Christopher Vakoc. Photo from CSHL

By Daniel Dunaief

Diseases like cancer take the normal raw materials of a cell and make them a part of a pernicious process that often threatens a person’s health.

Ideally, when researchers find the raw materials cancers need to survive, they discover specific proteins that are necessary for cancer, but aren’t critical for healthy cells.

That appears to have happened recently in the lab of Cold Spring Harbor Laboratory Professor Chris Vakoc in the study of the blood disease Acute Myeloid Leukemia, or AML.

Vakoc’s former graduate student Sofya Polyanskaya, who now works in a pharmaceutical company in Germany, discovered the importance of an understudied protein called SCP4, which removes phosphate groups from other proteins, in some forms of AML. This protein acts as an enzyme, which makes it a particularly appealing target.

In his lab, Vakoc said he and his researchers take “genes and the proteins they encode and [try to] publish the first paper linking them to cancer,” Vakoc said.

Polyanskaya and Vakoc recently published their findings in the journal Cell Reports.

These scientists disabled proteins in a host of diverse cancer types, looking for dependencies that were unique to each cancer. After determining that SCP4 was only needed in leukemia and not other cancers, they inactivated the protein in normal, healthy blood cells and found that it wasn’t needed.

“Leukemia cells are super sensitive to the loss of this enzyme,” Vakoc said.

Vakoc praised the work of Polyanskaya, who he said conducted the “inspiring work” that led to this conclusion. “It’s not easy for a brand new scientist entering the field to write the first cancer paper on a target.”

Polyanskaya surveyed hundreds of these enzymes to find a potential new protein that cancer, specifically, might need. The CRISPR technology, which didn’t exist nine years ago, provides a way of altering a large number of potential enzymes to find the ones that are critical for cancer’s survival.

Ideally, this kind of analysis enables researchers like Polyanskaya and Vakoc to focus in on the ones that are critical to cancer, but that don’t perform any important function in normal cells.

One of the other benefits of this work is that it validates the importance of targets that have become the focus of other research projects.

“Part of what we’re doing is making sure that our processes more broadly in the field are robust,” Vakoc said. “We are more confident in other targets we didn’t discover” but that play a role in the progression of leukemia.

To be sure, the discovery of the SCP4 target is the first step in a series of questions that may require considerable time and resources to ensure a reliable and safe clinical benefit.

As with many cancers, leukemia may have the equivalent of a back up plan, in case this seemingly important enzyme is unavailable. Indeed, the battle against cancer and other diseases involves moves and counter moves by pharmaceutical and biotechnology companies and the diseases they battle.

Additionally, researchers like Vakoc need to discover the reason cells produce this enzyme in the first place. Mice lacking SCP4 are born, but develop metabolic stress after birth.

“The important experiment in the future will be to determine what the consequences of targeting SCP4 are in normal tissue much later after birth,” Vakoc explained in an email.

Like other cancers, leukemia is a heterogeneous disease, which is another way of saying that not everyone with the disease has the same symptoms and prognosis and not everyone would respond to the same treatment in the same way.

Vakoc would like to figure out for “which subset of patients with leukemia is this protein the most important. Down the road, that could help determine who might benefit from an SCP4 inhibitor.

“We want to personalize therapy as much as possible,” he said.

In his follow up research, Vakoc hopes to learn more about the three-dimensional structure of the protein complex.

Vakoc’s interest in leukemia stems from his interest in studying blood. When he conducted his PhD training at the University of Pennsylvania, he studied normal blood development.

He was particularly interested in pediatric cancer. While AML is on of the cancers that children can develop, it is far more common in elderly people.

The lab has a strong focus on leukemia.

Vakoc, whose lab is next door to CSHL Cancer Center Director David Tuveson, has also starting searching for potential therapeutic targets in pancreatic cancer.

He is excited about the potential to bring attention to a possible candidate that may provide a therapeutic benefit for patients at some point.

“It feels good to put a new target on the map,” he said.

The CSHL scientist recognizes that cancer can and often does develop resistance to a treatment that tackles any one enzyme or protein. Still, he said treating cancer with any new and effective therapy could extend life by several months, which are often “very valuable to patients.”

Vakoc suggested that any potential new treatment for leukemia would likely involve several drugs working together to stay ahead of cancer.

“The real hope and optimism is that, if you had a copule of targets like this that are not needed in healthy cells, you could add 10 or 20 years of high quality life. You could keep the disease in a chronic, latent state.”

Camila dos Santos. Photo courtesy of CSHL

By Daniel Dunaief

Pregnancy and lactation can alter genes in specific mammary cells, which may have implications in a defense against cancer.

In mouse models, mice that became pregnant at a young age have so-called epigenetic changes that survive for the animal life span and some of those are linked to a decrease in breast cancer.

In a recent study published in Cell Reports, Cold Spring Harbor Associate Professor Camila dos Santos and her graduate student Amritha Varshini Hanasoge Somasundara found that a protein involved in mammary cells in mice, called CD1d, boosts the immune system after a full pregnancy cycle, protecting it against breast cancer.

“Our research demonstrated that increased levels of CD1d in breast cells serve as a signal to recruit higher numbers of specialized immune cells” called natural killer T-cells, or NKT, “to come and reside within the breast tissue after pregnancy,” dos Santos explained in an email. These NKTs are part of mechanisms that reduce breast cancer risk after pregnancy.

Dos Santos would like to understand the molecular changes that occur from pregnancy and hopes one day to adapt them in the form of a vaccination or pill to decrease the risk of breast cancer.

To be sure, numerous questions about the process of using the immune system to prevent cancer remain, which means that the development of such a preventive pill requires considerable additional research.

Dos Santos has spent the last eight years developing model systems that allow her to discover pregnancy-induced changes that could lead to preventive strategies.

Enhancing the communication between epithelial and immune cells could represent a way to decrease breast cancer development and even treat cases of developed cancer.

To get to that point, dos Santos, the members of her lab, and her collaborators plan to make discoveries like this one to understand the dynamic interaction between the cascade of molecular interactions from pregnancy and the genetic and immunological reactions.

Humans have four CD1 genes, which all play a similar role in immunity. Additionally, there are several types of NKT cells, and each of them has a different immunological function, which means that any prevention or treatment that tapped into this system would need to bring the right CD1 molecule and the right NKT cells.

It is not yet clear whether enhancing CD1 signals protect women who might have a predisposition to breast cancer. Dos Santos is currently exploring this question in animals.

While dos Santos is focusing specifically on pregnancy-driven changes in the mammary gland, she acknowledged that altering CD1d levels in other organs might also decrease other types of cancer.

Dos Santos described pregnancy as being akin to turning on a light. First, during the course of gestation, pregnancy brightens that light to the top. After birth, the dimmer goes to the middle, leaving the system in a different state, which is not only more prepared for the next pregnancy but also to defend itself against alterations like cancer.

In most pregnancy mammary cells in mice, the scientists found a 10-fold increase in the abundance of NKT cells when compared to cells from an individual who had never been pregnant.

When the researchers removed the CD1d protein in mice, they found an association between the absence or low expression and the development of tumors in the breast.

Dos Santos and Hanasoge hypothesize that this protein is recruiting immune cells to monitor breast cells after pregnancy. If the epithelial cells develop cancer, the NKT cells may kill them, preventing the development and advancement of cancer.

In addition to working with mouse models of pregnancy, dos Santos is collaborating with Northwell Health to study cells from healthy women who are undergoing cosmetic surgery. They are analyzing that data, which wasn’t in this paper. 

Dos Santos is investigating several questions, including how the age at pregnancy influences breast tissue. She is creating organoids, which are three-dimensional models of breast cells that react to change in their environment

Joining a family

From left, Amritha Varshini Hanasoge Somasundara and Camila dos Santos

Amritha Varshini Hanasoge Somasundara, who has been a part of dos Santos’s lab for over two years, explained that she felt comfortable and supported instantly when she arrived. She described the atmosphere as extremely collegial and felt as if she were included in a scientific family.

Joining dos Santos’s group was “possibly the best decision I’ve ever made,” said Hanasoge. Dos Santos’s lab is a “really special place” where lab members often have lunch together and support each other’s research.

Hanasoge was drawn to Dos Santos’s mentorship and the overall lab dynamic. Scientifically, she was also interested in the immunology project, exploring NKT cells. Her main project has involved trying to characterize NKT cells further. 

Hanasoge sees plenty of opportunities to address additional questions in this field. “We don’t know if the process of lactation is causing more CD1d and increasing expression,” she said. “We are still trying to characterize what T-cell receptors are being expressed after pregnancy.”

A resident of Syosset, Hanasoge enjoys reading and said she was fascinated by science when she was growing up in Mysore, Kamataka in India. She asked her parents for a microscope when she was around seven and used it to looked at flower petals and leaves. That toy microscope, which her parents purchased from a science museum in Mumbai, is still in her parent’s house.

Hanasoge is eager to combine basic and translational work and hopes her research has a clinical benefit. She is looking forward to the next steps in her research in dos Santos’s lab.

“I learn from her every day by watching how she interacts with people she mentors, both inside the lab and out,” Hanasoge explained in an email. “Her passion and commitment to being a good mentor and her drive to ask the right questions in our research are inspiring.”

 

From left, Daniele Rosado and Ullas Pedmale examine a sample of the model plant Arabidopsis. Photo courtesy of Ullas Pedmale

By Daniel Dunaief

Many plants are in an arms race akin to the developers of skyscrapers eager to get the most light for their prized penthouse apartments. Only, instead of trying to collect rent from well-heeled humans, these plants are trying to get the most sun, from which they create energy through photosynthesis.

Plants are so eager to get to the coveted sunlight that the part growing towards the light sends a distress signal to the roots when they are in the shade. While that might help an individual plant in the short term, it can create such shallow and ineffective roots that the plant becomes vulnerable to unfavorable weather. They also can’t get as many nutrients and water from the ground.

This is problematic for farmers, who want plants that grow in the sun, but that don’t sacrifice the development of their roots in the shade. Ullas Pedmale, Assistant Professor at Cold Spring Harbor Laboratory, is working to lend a hand.

Pedmale, who recently published research in the journal Plant Physiology, is studying the signals the shoots, or the parts of the plants either in the sunlight or the shade, send to the roots.

Pedmale and postdoctoral researcher Daniele Rosado, who is the first author on the recent paper, explored the genes that turned on in the roots of the model plant Arabidopsis and tomato plants when these plants were in the shade.

When plants are in the shade, they “prioritize shoot growth and try to outcompete the neighboring plants,” said Rosado. “That’s when root development is compromised.”

Among the genes that are active when plants are in the shade is a family of genes called WRKYs, which affect gene expression and cause stunted growth in the roots.

WRKY genes respond to stress. Keeping WRKY genes on all the time, even when a plant is in the sun, caused stunted growth of the roots. WRKY proteins turn on or off other genes.

This can be problematic for farmers, who tend to try to increase yield by putting more plants in an area. At that point, the plants shade each other, which is “bad for the root system. If we can find a way to get the roots to grow normally, we can potentially increase yield,” Rosado said.

This could also remove more carbon dioxide from the air and store it in the developing roots, helping to mitigate the effect of global warming. “Our study can give a roadmap on how to make longer, deeper roots,” Pedmale said.

At this point, researchers still don’t know how the plant transfers information about the amount of sunlight it receives in the green chloroplasts where photosynthesis occurs to the WRKY genes, which are in the nucleus.

Researchers have been studying the shade response in the shoots of plants for over five decades. They have not, however, focused as much attention on the effect of less sunlight on the roots.

“We want to tackle this problem,” Pedmale said.

WRKY genes are a generalized stress signal, which is not just involved when a plant isn’t getting enough light. They are also turned on during pathogen attacks, stress and amid developmental signals.

Indeed, plants in the shade that have turned on these signals are especially vulnerable to attacks. Caterpillars, for example, can eat most of a shaded plant because the plant is so focused on growing its shoot that its defenses are down.

When that same plant is in the sunlight, it is more effective at defending itself against caterpillars.

At this point, Pedmale doesn’t know whether these genes and signals occur across a broad species of plants beyond tomatoes and Arabidopsis. He and others are hoping to look for these genes in grasses and grains.

Pedmale is also searching for other signals between the shoot and the root. “Plants are masters of adaptation,” he said. “They might have redundant systems” that signal for roots to slow their growth while the shoots tap into the available energy to grow.

Plants may also have natural molecules that serve as brakes for the WRKY signal, preventing the shoot from taking all the available energy and rendering the plant structurally fragile.

A scientist at CSHL for five years, Pedmale came to the lab because of the talent of his colleagues, the reputation and opportunity at CSHL and the location.

Born and raised in Bangalore, India, Pedmale enjoys reading fiction and autobiographies and wood working when he’s not in the lab. He recently made a book shelf, which provides him with a chance to “switch off” from science, which, he said, is a 24-hour job. He has taken wood pieces from his workshop and brought them to PhD classes at CSHL, where he can show them plant biology and genetics at work.

Pedmale and his wife Priya Sridevi, who also works at CSHL, have a mini golden doodle named Henry.

A native of São Paulo, Brazil, Rosado is married to plant biologist Paula Elbl, who is the co-founder of a start up called GALY, which is trying to produce cotton in a lab instead of in a field.

Rosado is the first in her family to attend a public university. She has been working in Pedmale’s lab for two years and plans to continue her research on Long Island for at least another year.

Rosado knew Pedmale had worked as a post doctoral researcher in the lab of celebrated plant biologist Joanne Chory at the Salk Institute for Biological Studies. She met Pedmale at a plant conference, where she expressed an interest in his research.

Longer term, Rosado hopes her research has a broader impact.

“If I’m lucky, I’ll be able to see the fruits of my work being applied to make a difference and help feed people,” she said.

As for his work, Pedmale is eager to understand and use the signals from one part of a plant to another, given that the plant lacks a nervous system. “Once we can understand their language,” he said, “we can manipulate it to increase yield.”

Jessica Tollkuhn Photo courtesy of CSHL

By Daniel Dunaief

They are like directors in a carefully choreographed production, instructing certain groups that become active, while giving others a five-minute break.

In the case of the human body, directors take many forms, including hormones; the same hormones that can transform adorable, sweet and well-behaved children into smelly, strong-willed teenagers.

Hormones like estrogen, testosterone and progesterone affect people at various ages and in different ways.

Recently, Cold Spring Harbor Laboratory Assistant Professor Jessica Tollkuhn and her graduate student Bruno Gegenhuber teamed up with University of California at San Francisco Herzstein Professor of Molecular Physiology Holly Ingraham to link the way estrogen in a specific area of the brain turns on particular genes.

For mice that are representative of post-menopausal women, the lower activity of a gene called melanocortin-4, or MC4R causes these mice to become less active.

By activating MC4R neurons in the ventrolateral ventromedial hypothalamic nucleus of the brain in the absence of estrogen, researchers caused a dramatic increase in physical activity and 10 percent body weight loss after one day.

Additionally, turning up the MC4R gene increased their bone density over time.

Linking the gene activated by estrogen in a part of the brain that affects how adult females use energy, the scientists provided a causative link that explains lower energy in this population.

Tollkuhn said her contribution showed that the estrogen receptor binds DNA in the presence of hormones.

The scientists published their research in the journal Nature.

“If anything, this paper is a study of how just one gene can show this exquisite behavioral response,” Tollkuhn added.

The MC4R gene is also found in the male brain, although not in the same area. Experimentally, turning up the gene also increases physical activity in males.

Numerous drugs currently target this gene in connection with increasing libido in post-menopausal women. Using these treatments for other issues, like weight gain and activity level, would require additional study.

Estrogen affects numerous other areas of the body, including some that may cause other problems. Hormone replacement therapy has contributed to the development or worsening of other cancers, such as breast cancer, although it is not clear why or how this happens.

“There’s evidence that there can be positive benefits [like bone and mental health], but also evidence that it can increase the risk of cancers,” Tollkuhn said.

Ingraham knew Tollkuhn from their overlapping research experiences at the University of California at San Diego and, later at UCSF.

Ingraham had reached out to Tollkuhn to see if the experiments in Tollkuhn’s lab could determine the link between the hormone and the MC4R gene.

“It’s always a challenge in biology to get a direct causality” because numerous factors in a living system could contribute to the development of a condition or a behavior, Tollkuhn said.

Tollkuhn suggested that the bulk of the experiments were done in Ingraham’s lab.

Ingraham recognized early on the benefit of finding these direct binding sites.

“We are saying, ‘Here is a hormone and it is acting through this molecule and it’s causing this change … that we know is really important for eliciting this behavior,” Ingraham said.

Ingraham, who worked with Tollkuhn when she was a post doctoral researcher and Tollkuhn was a graduate student in Geoffrey Rosenfeld’s lab at UC San Diego, called her colleague “really talented” and said she “spent years working this whole system out. It’s heroic and nobody else has done it.”

Ingraham sent Rosenfeld a message after the journal Nature accepted their paper, indicating his trainees had “hit pay dirt on this one.”

Ingraham hopes the paper motivates other researchers to think about entering this area and tackling this challenge, which is so important for women’s health.

“The only way we’re going to move forward for women’s health is to understand all these different facets of what estrogen is doing in the brain,” she added.

In press coverage of the research, Ingraham described the comments as falling into two categories. In the first, women suggest that they’re past menopause and have never been more active. In the second, women indicate that getting hormone replacement therapy genuinely helped them, including with brain fog.

Other scientists have sent Ingraham congratulatory emails about the paper. They have “appreciated that this had such a great molecular story,” she said.

In a broader research context, Tollkuhn is interested in determining how hormones affect the brain during sexual differentiation.

She is now focused on identifying a new repertoire that she and others can explore in future studies.

Tollkuhn’s lab is also investigating how estrogen influences brain development. She has found dozens of genes she would like to understand in the kind of detail with which she explored MC4R. Estrogen receptors also are connected to HTR1A and HTR1D, which are genes for serotonin receptors and may connect estrogen to mood.

Studies in scientific literature have shown that numerous psychiatric and neurological conditions have sex differences in terms of their impacts on men and women.

“We have these pieces and we can try to put together this puzzle,” Tollkuhn said. “We can try to understand why this would be the case. The long term goal is to figure out why there is a greater increase in [certain diseases] in men or women, which could lead to the development of better treatment.”

Tollkuhn is also interested in understanding the progression of neurodegenerative conditions like Alzheimer’s, which is twice as likely in women as in men. The symptoms for this disease develops more rapidly in post menopausal women, who typically have a more precipitous decline in estrogen than older men do in their levels of testosterone.

“I’m interested in what hormone receptors are doing in the brain,” she said.

Semir Beyaz (center) with research assistant Onur Eskiocak, left, and graduate student Ilgin Ergin. Photo by Gina Motisi/CSHL

By Daniel Dunaief

High fat diets present numerous health problems for humans and mice, which are often used as a model organism to understand disease.

In a recent multi-disciplinary study with mice, Cold Spring Harbor Laboratory Fellow Semir Beyaz and 32 colleagues from 15 other institutions explored how a high fat diet affects the development of intestinal tumors.

Semir Beyaz. Photo by Gina Motisi/CSHL

The diverse team of scientists brought together a range of expertise to discover the way a high fat diet disrupts the cross talk among the microbiome, stem cells and immune cells, triggering tumors through the reduction in the expression of an important gene, called major histocompatibility complex II, or MSC-II.

“This work nicely integrates efforts in stem cell biology, immunology, microbiology and metabolism in the context of understanding how diet is linked to cancer,” Beyaz explained in an email. With such interdisciplinary studies, “we hope to improve our understanding” of the mechanisms that link nutrition to diseases.

The paper, published in Cell Stem Cell, for which Beyaz is the first and corresponding author, shows how a high fat diet leads to immune evasion of tumor initiation stem cells due to the suppression of the immune recognition molecule MHC-II.

At the center of this study, the MHC-II gene encodes a protein that presents antigens, or foreign substances, to the immune system. When a cell is infected or cancerous, immune cells detect the unwelcome agents through their surveillance of MHC molecules, Beyaz said.

A high fat diet also results in the alteration of immune cells in the micro environment and the signals that they produce, called cytokines.

“The novel finding of our study is that the crosstalk between stem cells, microbes and immune cells is critical for eliminating tumor initiating cells and this cross talk is dampened in response to a high fat diet, demonstrating a mechanistic basis for how high fat diets may promote cancer,” said Beyaz.

A current hypothesis, which has some supporting evidence in Beyaz’s study, suggests that diet-related factors might facilitate early onset colorectal cancer.

To be sure, researchers need to conduct more work to understand the environmental factors that facilitate early onset colorectal cancer, Beyaz explained. “The knowledge of what causes early onset colorectal cancer in young adults is very limited,” he added.

Semir Beyaz with visiting clinical researcher Aaron Nizam (left) and research tech Katherine Papciak. Photo by Gina Motisi/CSHL

Beyaz believes diet is one of the most important environmental factors that contribute to cancer risk. Diet could affect sleep, stress and other factors.

“There are so many things we don’t know about how diet affects our body,” he said. “That’s why I’m very excited to work on understanding these mechanisms.”

Beyaz said the mice in his study consumed a lard-based pro-obesity diet that was high in carbohydrates.

A diet that is lower in carbohydrates and higher in fat is more similar to a ketogenic diet, which could have other outcomes. His ongoing studies are trying to tease apart some of these differences.

To counteract the effect of diet on the development of cancer, Beyaz plans to activate the altered pathways by using either microbes or small molecule drugs.

“We believe if we promote immune surveillance by activating these pathways, we can elicit preventative and therapeutic strategies against cancer,” he explained.

Additionally, in his ongoing research, Beyaz plans to address numerous other questions that link diet to disease.

An increasing number of studies are exploring how diet and microbes affect cancer, which he described as a “hot topic.”

Beyaz believes a high fat diet might turn on or off some genetic sequences, enabling the latent development of cancer.

His unique niche involves searching for a connection between diet and perturbations that affect cross talk among cells. While this field has numerous challenges, Beyaz suggested he was “drawn” to that difficulty.

Beyaz’s expertise is in stem cell biology and immunology. He appreciates and enjoys the opportunity to interact with researchers from other disciplines that could lead to actionable progress.

Hannah Meyer. Photo from CSHL

While science has to be reductionistic and focused on one molecule or cells at times, new conceptual and technical advances have made it possible for the lines between disciplines in biology to disappear slowly, he explained.

Beyaz and his colleagues are looking forward to taking some of the next steps in this effort.

For starters, he is excited to expand this study, to understand whether there is a threshold for a high fat diet that favors the growth of tumors. Diets that fall below a potential threshold might not promote the growth or development of tumors.

Such a threshold could become clinically relevant, providing health care workers with a pre-cancerous marker that could signal the need for lifestyle changes and medical vigilance that could stave off or avoid the formation of disease-bearing and life-threatening tumors.

“We have some ongoing work to delineate such thresholds and proxies,” Beyaz said. Additionally, they would like to see whether this effect is reversible, to determine whether an altered microbiome might promote the expression of MHC-II, which could derail the tumor forming process.

Pawan Kumar. Photo from SBU

Beyaz’s collaborators on this work include Hannah Meyer, who is a fellow at Cold Spring Harbor Laboratory Fellow, and Pawan Kumar, who is an Assistant Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University.

In his life outside the lab, Beyaz, who enjoys fishing, gardening, and hiking, avoids excessive sugar and fat consumption. He doesn’t eat fast food or consume sugary drinks.

Originally from the town of Samandag which is near the Mediterranean Sea in the southeastern part of Turkey, Beyaz enjoys cooking and is fond of making lamb, beef, chicken and eggplant kebabs.

When he was growing up, Beyaz said science was a passion for him.

“It is not a job or a career,” he explained. “It is the way I find meaning in life, by learning how to ask and (sometimes) answer questions at the edge of cumulative human knowledge.”

Chemist John Moses on the campus of Cold Spring Harbor Laboratory. Photo from CSHL

By Daniel Dunaief

If you build it, he will come.

That’s an iconic line from the movie “Field of Dreams,” starring Kevin Costner, in which a mythical voice calls to the Iowa farmer, encouraging him to plow through his corn to build a baseball field so the ghosts of past baseball players can entertain a modern audience.

It seems only fitting that this year, in which Major League Baseball hosted its first professional game in Iowa near the set of the popular movie, chemists have built something they hope brings together numerous other chemicals to produce products with various applications, from drug discovery to materials science.

About 120 years ago, researchers in France discovered a highly reactive gas called thionyl tetrafluoride, whose chemical symbol is SOF4.

The gas has numerous potential applications because researchers can control its reactions and derivatives. Scientists can swap each sulfur-fluorine bond with a bond between sulfur and something with desirable properties or applications.

While the gas serves as a potential building block, it is scarce and is not commercially available.

Thionyl tetrafluoride is “very reactive,” said chemist and Cold Spring Harbor Laboratory Professor John Moses. “It’s not something the Average Joe wants. It’s dangerous chemistry.” It was largely overlooked until the 1960’s, when chemists at DuPont reinvestigated it.

Once Suhua Li, the lead author of a recent paper in Nature Chemistry and a former post doctoral researcher in Nobel-prize winner K. Barry Sharpless’s lab at Scripps Research Institute in La Jolla, California, generated more of this gas, the team could work together to determine the types of connections that might be possible. 

While the research was a group effort in terms of planning and ideas, Li, who did the vast majority of the synthesis of the gas, is “the hero,” Moses said. “The gas itself, and reagents used to make the gas, are potentially very dangerous, and it takes courage and confidence to attempt such chemistry. ([Li] even had a bit of a mishap, to say the least, but still went ahead and tried again.”

Moses also appreciates how “ideas are just ideas until somebody takes the initiative to put them into practice.”

Moses, Sharpless, and Scripps Research Institute Associate Professor Peng Wu developed the polymer chemistry, while Hans Zuilhof of Wageningen University in the Netherlands helped elucidate the helical structure of the polymers.

The team used a technique Sharpless calls “click chemistry” to explore the substances they could create with this gas.

Thionyl tetrafluoride acts like a lego building block that can be connected with other building blocks in several dimensions.

Click reactions create defined products with absolute reliability, Moses explained. Scientists get what they expect, which is not always true in chemistry.

“In some reactions, you take A and B and you don’t always get C,” Moses said. “You get C as a major product, but you also get D, E and F.”

In click chemistry, however, the combination of A and B is guaranteed to produce C.

Some click reactions run better in water, or at least when water is present. Water is non-toxic, inflammable, inexpensive and a good heat sink.

Click philosophy is about using reliable reactions for the purpose of function discovery.

With thionyl tetrafluoride, Li and the other researchers made about 30 polymers, each of which had original structures using different fragments.

The group managed to attach antibiotics to a thionyl tetrafluoride-derived polymer and demonstrated that it retains antibacterial function.

As long as the module has a handle to exchange with the sulfur-fluorine bond, the gas has a broad range of potential applications.

With thionyl tetrafluoride as his inspiration, Moses coined the term multidimensional click chemistry, which identifies the gas a multi dimensional hub.

The chemists used a regular party balloon to transfer the gas, which is connected to a syringe and a needle. They inserted the needle through a rubber septum into a sealed flask. The reaction with reagents in the flask is straightforward to perform once the gas is available, Moses said.

Born and raised in Wrexham, North Wales, a town aglow after actors Ryan Reynolds and Rob McElhenney last year bought a 156-year-old local soccer team, Moses had no interest in science when he was young, although he was curious about life in general.

He left school to work in a factory that made life rafts and buoyancy jackets when he was 16.

The factory had a distinct odor of toluene and glue.

“It was dreadful,” he recalls. “I was lucky to escape that life.”

He eventually landed an apprenticeship at a company called App-Chem, that allowed him to study physics and chemistry in college one day per week. 

Michelle and Paul Paternoster

By Daniel Dunaief

Part 2

Three families and their foundations jump-started a research mission on Long Island that offers a chance for change. Their stories reflect a desire to remember their family members and a need to offer hope and help to others.

Christina Renna

Christina Renna with sister Rae Marie Renna

Phil Renna waited while his 16-year old daughter Christina spoke with her doctor. He and his wife Rene had decided to allow their daughter, who was battling a form of connective tissue cancer called rhabdomyosarcoma (RMS), to be involved in decisions about her treatment.

When Christina came out of the room, Phil, director of operations in the communications department at Cold Spring Harbor Laboratory, asked if he should also speak with the doctor. Christina said it wasn’t necessary. On the way home, she told him it had to be a “really good Christmas.”

He knew what that meant, although she also asked him not to tell anyone how close she was to the end of her life.

Renna and parents throughout the country have had to cope with the agony of rhabdomyosarcoma, which mostly affects children. People battling this cancer have turned to medicine for help, only to find that the treatment options are limited.

That, Renna and others say, was as unacceptable to them when their children were battling cancer as it is now, when the next generation is struggling with this illness.

RMS doesn’t receive the same level of funding nationally as cancers that affect more people, such as breast, lung and prostate cancer, but the agony and suffering are just as significant.

Amid their battles with the disease, families have turned to their support groups, including friends, extended family, and community members to raise funds for basic research, hoping grass roots efforts allow future generations to have longer, healthier lives.

Supported by these funds and a willingness to fill a research gap, Cold Spring Harbor Laboratory CEO Bruce Stillman has backed efforts to gather information and to support research that may also help people with other forms of cancer.

Renna, who lives in Lindenhurst, struggled with his role as father and protector when Christina developed rhabdomyosarcoma.

“I’m supposed to protect my kids,” Renna said. “I should be able to tell them, ‘It’s going to be okay.’”

Renna went to Stillman to ask whether Christina, who was a patient at Memorial Sloan Kettering, might get better care somewhere else.

After conducting some research, Stillman told his colleague about the lack of basic research and other treatment options.

“That was a crushing moment for me,” Renna said.

During treatment, Christina had to be at Memorial Sloan Kettering at 7 a.m., which meant he and Christina’s mother Rene got in the car at 5 a.m. with their daughter.

Renna dropped them off, drove back to work, where he’d put in a full day, drive back to the hospital and return home at 10:30 p.m.

“That was every night, five days a week,” Renna recalled. While those were tough days, Renna said he and his wife did what they needed to do for their daughter.

Five years after his daughter died at the age of 16, Renna drove home from work one day to find his shirt was wet. It took him a while to realize the moisture came from the tears, as he cried his way back to his house. At one point, he thought he had post-traumatic stress disorder.

Renna continues to raise money to support research into this disease, while also helping people create and develop their own foundations, often after enduring similar pain.

“Every single foundation that has come and given money to the lab, I have personally met with,” he said. “I helped our advancement team onboard them.”

As someone who has lost a child and understands what a parent can be feeling, Renna is committed to helping others cope with their grief. 

“For me, it is about helping the lab, but also about helping families honor the memory of their child in a meaningful way and what better way than to help another family and perhaps find a cure,” he wrote in an email.

Renna believes investments in research will pay off, helping to answer basic questions that will lead to better treatments down the road.

So far, the foundation has given $387,300 to Cold Spring Harbor Laboratory for research. They also gave $50,000 to Make-a-Wish in Suffolk, and $25,000 to local scholarships. The foundation supported Memorial Sloan Kettering with an iPad program. Ultimately, Renna believes in the ongoing return from research investments.

“Everybody wants to find and fund the silver bullet,” he said. “Everybody wants to give money to fund a clinical trial. Basic research is where the discoveries are made.”

Renna urged people creating foundations to have a strong board that included business people and that might also have a scientific or medical advisory element. He also suggested funding foundations a year ahead of time. That helped his foundation in 2020, when finding donors became more challenging during the pandemic.

Being at Cold Spring Harbor Laboratory and helping others get through darker days that are all too familiar to him gives Renna comfort. “I know, in some way, every single day, I’m making an impact,” he said. “How measurable it is, I don’t know. There are days when I’m pretty proud.”

As far as he feels they have come, Renna said it’s not the time to look back, but to press ahead.

T.J. Arcati

A former summer intern in Bruce Stillman’s lab when he attended Notre Dame, T.J. Arcati was married and had two children when he succumbed to sarcoma.

“We know what we went through,” said his father, Tom Arcati, an oral and maxillofacial surgeon in Huntington. “He left a son and a daughter without a dad.”

Tom and his wife Nancy, who raised T.J. in Lloyd Harbor and live in Huntington, were with their son for his treatments and therapies.

Tom and Nancy Arcati are determined to extend people’s lives by more than a year or two and are actively engaged with other families who are coping in the midst of the cancer storm. “I’m talking to people now that unfortunately are going through what we did seven years ago,” Tom Arcati said.

While the Arcatis support other families, their empathy “brings you back to a place you never really leave,” Nancy Arcati said. These interactions “keeps T.J.’s life on people’s minds and in their hearts.”

Tom Arcati tries to be a source of solace to people who are trying to gather information.

In the aftermath of TJ’s death at the age of 34, Arcati reached out to Stillman to see if the lab could work towards better treatments.

One Saturday, Arcati and his son Matthew went to Stillman’s house, where they sat in his living room, with Stillman drinking tea and Arcati having coffee.“What do you think?” Arcati recalled asking. “Are you going to do sarcoma research?” Stillman looked back at his guest and mentioned that he was thinking about it. Stillman called Arcati a few days later.

“When he called me, he said, ‘We’re a cancer institute. We should be doing sarcomas.’ That’s how I remember this whole thing going down. It was pretty heart warming.”

The first step for CSHL was to host a Banbury conference. The site of international meetings on a range of scientific topics since 1978, the Banbury center brings together experts in various fields. The meetings provide a forum for scientific advances and result in various publications. By holding a Banbury Center meeting, CSHL helped advance research into sarcomas.

The Arcatis have remained active in the Friends of T.J. Foundation, which TJ and several college friends founded in 2009 after T.J. was diagnosed with sarcoma. They have stayed in close contact with CSHL Professor Chris Vakoc and his PhD student Martyna Sroka, who regularly keeps him informed of her progress. Sroka has spoken at some of the outings for the Friends of TJ Foundation. This year, Stillman will speak at the September 13th fundraiser at the Huntington Country Club.

“It’s really imperative that people who are supporting us know what their dollars are being spent on,” Arcati said.

The Friends of TJ Foundation has raised about $50,000 each year, bringing their total fundraising to about $400,000.

Arcati hopes something positive can come out of the losses the families who are funding Vakoc’s research suffered.

“If we can save one kid’s life somewhere by doing what we’re doing, then this whole process is worth it,” Arcati said.

Michelle Paternoster

Michelle Paternoster of Lindenhurst developed sarcoma in her sinuses. Her husband Paul Paternoster helped her through 38 surgeries, over 90 radiation treatments and several rounds of chemotherapy.

Michelle and Paul Paternoster

The couple tried immune therapy in the Bahamas in the fall of 2008 and went to New York in 2011 for treatment.

“We drove [to the city] for 90 days” excluding weekends, Paternoster recalled. The treatments seemed to have a positive effect during the trial, but shortly afterward, the cancer continued growing.

After Michelle died in 2013 at the age of 34, Paternoster was determined to help others, initially asking supporters to contribute to the fundraising effort from the Arcatis.

Donations to the Friends of T.J. Foundation reached $30,000, which helped underwrite the Banbury conference at Cold Spring Harbor Laboratory. Michelle and T.J. had seen each other in the radiation suite in the halls of Memorial Sloan Kettering.

Paternoster then started the Michelle Paternoster Foundation for Sarcoma Research. The President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, Paternoster wanted to help people at a clinical level.

Through Michelle’s Clubhouse, he partnered with the Children’s Hospital of Pittsburgh, paying for hotels of pediatric cancer patients when the Ronald McDonald house is full. The clubhouse also provides gift cards to help pay for gas, tolls and copays on prescriptions.

“Knowing how difficult it is to go through this, I can’t imagine what it’s like to not have that capability” to pay for basic needs during treatment, Paternoster said. “That is why it is so important for our board to do something at the clinical level to support families in this battle.”

Paternoster said the relatively small but growing size of the group dedicated to helping each other makes each person’s contribution that much more important.

“Normally, when you’re doing any kind of charity work, you feel like you’re a tiny part of this project, especially when it comes to [diseases like] breast cancer and things that impact millions of people,” Paternoster said. When he attended the Banbury conference that launched the research effort at Cold Spring Harbor Laboratory, he said “you felt you could make a difference. You’re sitting in a room with 25, 30 people max. That was the entire effort to eradicate this disease.”

Paternoster, who lives in Cold Spring Harbor, called the collaboration that came out of the meeting “astounding.”

The Michelle Paternoster Foundation has raised $500,000, with about $350,000 of that supporting the work at Cold Spring Harbor Laboratory.

Ultimately, like the other families who raise funds, stay informed and offer help to strangers battling an all-too-familiar disease, Paternoster feels that the opportunity to make a meaningful contribution inspires him.

“That’s our dream,” he said, “to find a cure, so other people don’t have to feel what we felt.”

To read Part 1 of the article click here.

Martyna Sroka. Photo by Sofya Polyanskaya

By Daniel Dunaief

Part 1:

A group of people may prove to be the guardian angels for the children of couples who haven’t even met yet.

After suffering unimaginable losses to a form of cancer that can claim the lives of children, several families, their foundations, and passionate scientists have teamed up to find weaknesses and vulnerabilities in cancers including rhabdomyosarcoma and Ewing sarcoma.

Rhabdomyosarcoma affects about 400 to 500 people each year in the United States, with more than half of those patients receiving the diagnosis before their 10th birthday. Patients who receive diagnoses for these cancers typically receive medicines designed to combat other diseases.

 

Christopher Vakoc. Photo from CSHL

A group of passionate people banded together using a different approach to funding and research to develop tools for a different outcome. Six years after the Christina Renna Foundation and others funded a Banbury meeting at Cold Spring Harbor Laboratory, the grass roots funders and dedicated scientists are finding reasons for optimism.

“I wish I could run up to the top of a hill and scream it out: ‘I’m more hopeful than I’ve ever been,’” said Phil Renna, director of operations, communications department at CSHL and the co-founder of the Christina Renna Foundation. “I’m really excited” about the progress the foundation and the aligned group supporting the Sarcoma Initiative at the lab has made.

Renna and his wife Rene started the foundation after their daughter Christina died at the age of 16 in 2007 from rhabdomyosarcoma. Renna’s optimism stems from work Cold Spring Harbor Laboratory’s Christopher Vakoc, a professor and Cancer Center co-director and his research team, including PhD candidate Martyna Sroka have performed.

The cause for optimism comes from the approach Vakoc has taken to cancers, including leukemia.

Vakoc has developed a way to screen the effects of genetic changes on the course of cancer.

“Usually, when you hear about a CRISPR screen, you think of taking out a function and the cell either dies or doesn’t care,” Sroka said, referring to the tool of genetic editing. Sroka is not asking whether the cell dies, but whether the genetic change nudges the cellular processes in a different direction.

“We are asking whether a loss of a gene changes the biology of a cell to undergo a fate change; in our case, whether cancer cells stop growing and differentiate down the muscle lineage,” she explained.

In the case of sarcoma, researchers believe immature muscle cells continue to grow and divide, turning into cancer, rather than differentiating to a final stage in which they function as normal cells.

Through genetic changes, however, Sroka and Vakoc’s lab are hoping to restore the cell to its non cancerous state.

Cold Spring Harbor Laboratory has had success with other diseases and other types of cancer, which is where the optimism comes from, explained Paul Paternoster, President of Selectrode Industries, Inc. and the founder of the Michelle Paternoster Foundation for Cancer Research.

As a part of her doctoral research which she’s been conducting for four years, Sroka is also working with Switzerland-based pharmaceutical company Novartis AG to test the effect of using approved and experimental drugs that can coax cells back into their muscular, non-cancerous condition.

The work Sroka and Vakoc have been doing and the approach they are taking could have applications in other cancers.

“The technology that we’ve developed to look at myodifferentiation in rhabdomyosarcoma can be used to study other cancers (in fact, we are currently applying it to ask similar questions in other cancer contexts),” said Sroka. “In addition, our findings in RMS might also shed light on normal muscle development, regeneration and the biology of other diseases that impact myodifferentiation, e.g. muscular dystrophy.”

Martyna Sroka’s journey

Described by Vakoc as a key part of the sarcoma research effort in his lab, Martyna Sroka, who was born and raised in Gdańsk, Poland, came to Long Island after a series of eye-opening medical experiences.

In Poland, when she was around 16, she shadowed a pediatric oncology doctor who was visiting patients. After she heard the patient’s history, she and the doctor left the room and convened in the hallway.

Martyna Sroka. Photo by Sofya Polyanskaya

“He turned to me and said, ‘Yeah, this child has about a month or two tops.’ We moved on to the next case. I couldn’t wrap my head around it. That’s as far as we could go. There’s nothing we could do to help the child and the family,” said Sroka.

Even after she started medical school, she struggled with the limited ammunition modern medicine provided in the fight against childhood cancer.

She quit in her first year, disappointed that “for a lot of patients diagnosed with certain rare types of tumors, the diagnosis is as far as the work goes. I found that so frustrating. I decided maybe my efforts will be better placed doing the science that goes into the development of novel therapies.”

Sroka applied to several PhD programs in the United Kingdom and only one in the United States, at Cold Spring Harbor Laboratory, where she hoped to team up with Vakoc.

Sroka appreciated Vakoc’s approach to the research and his interest in hearing about her interests.

“I knew that we could carve out an exciting scientific research project that tries to tackle important questions in the field of pediatric oncology, [the] results of which could potentially benefit patients in the future,” she explained in an email.

The two of them looked at where they could make a difference and focused on rhabdomyosarcoma.

Sroka has “set up a platform by which advances” in rhabdomyosarcoma medicines will be possible, Vakoc said. “From the moment she joined the sarcoma project, she rose to the challenge” of conducting and helping to lead this research.

While Sroka is “happy” with what she has achieved so far, she finds it difficult at times to think about how the standard of care for patients hasn’t changed much in the last few decades.

“Working closely with foundations and having met a number of rhabdomyosarcoma patients, I do feel an intense sense of urgency,” she wrote.

Read Part 2 here.

 

Attendees at a conference at CSHL, an in-person tradition started in 1933. These conferences were suspended from 1943 to 1945 during WWII and were virtual during the pandemic in 2020 and for most of 2021. Photo by Miriam Chuai/CSHL

By Daniel Dunaief

For scientists, meetings and conferences aren’t just a chance to catch up on the latest research, gossip and see old friends: they can also provide an intellectual spark that enhances their careers and leads to new collaborations.

Amid the pandemic, almost all of those in-person conferences stopped, including the annual courses and meetings that Cold Spring Harbor Laboratory hosts. The internationally renowned lab has run meetings since 1933, with a few years off between 1943 and 1945 during World War II.

CSHL’s David Stewart. Photo by Gina Motisi/CSHL

While scientists made progress on everything from basic to translational research, including in laboratories that pivoted towards work on the SARS-CoV-2 virus, which causes COVID-19, they missed out on the kinds of opportunities that come from in-person interactions.

Assuming COVID infection rates are low enough this fall, CSHL is hoping to restart in-person conferences and courses, with the first conference that will address fifty years of the enzyme reverse transcriptase scheduled for Oct. 20th through the 23rd. That event was originally scheduled for October of 2020.

One of the planned guest speakers for that conference, David Baltimore, who discovered the enzyme that enables RNA to transfer information to DNA and is involved in retroviruses like HIV, won the Nobel Prize.

“I am hoping that there will be significant participation by many eminent scientists, so that is in itself somewhat [of] a ceremonial start,” wrote David Stewart, Executive Director of meetings and courses at Cold Spring Harbor Laboratory.

To attend any of the seven in-person meetings on the calendar before the end of the year, participants need to have vaccinations from either Pfizer, Moderna, Johnson & Johnson or AstraZeneca.

Attendees will have to complete an online form and bring a vaccination card or certificate. Scientists who don’t provide that information “will not be admitted and will not get a key to their room or be able to attend the event,” Stewart said.

CSHL also plans to maintain the thorough and deep cleaning procedures the lab developed. 

Stewart hopes that 75 to 80 percent or more of the talks presented will be live, with a virtual audience that could be larger than the in-person attendance.

“It is important to have a critical mass of presenters and audience in-person, but there’s no real limit on how large the virtual audience could be,” he explained.

Typically, the courses attract participants from over 50 countries. Even this year, especially with travel restrictions for some countries still in place, Stewart expects that the majority of participants will travel from locations within the United States.

The Executive Director explained that CSHL was planning to introduce a carbon offset program for all travel to conferences and courses that the facility reimburses starting in 2020. After evaluating several options, they plan to purchase carbon offsets from Cool Effect and will encourage participants paying their own way to do the same or through a similar program.

The courses, meanwhile, will begin on October 4th, with macromolecular crystallography and programming for biology. CSHL hopes to run six of these courses before the end of the year, including a scientific writing retreat.

“We are looking to 100 percent enrollment for our courses, so likely this year that will largely be domestic,” Stewart explained.

The courses, which normally have 16 participants, may have 12 students, as the lab tries to run these training opportunities safely without masks or social distancing.

From March of 2020 through the end of last year, the lab had planned 25 meetings and 25 courses. As the pandemic spread, the lab pivoted to virtual meetings. “I felt like a car salesman trying to sell virtual conferences,” Stewart recalled. For the most part, the lab was able to keep to its original schedule of conferences, albeit through a virtual format.

In addition to the scheduled meetings, CSHL decided to add meetings to discuss the latest scientific information related to COVID research. 

Stewart approached Hung Fan, a retired virologist at the University of California at Irvine, to help put together these COVID exchanges. Those meetings occurred in June, July, August, October, and January. The sixth one recently concluded.

The meetings addressed “everything around the science of the virus,” Stewart said, which included the biology, the origin, the genomics, the immune response, vaccines, therapeutics and diagnostics, among other scientific issues.

“There was a lot of excellent work being done around SARS-CoV-2,” Stewart said. “We were trying to identify that early on. It was helpful to have people who knew the field well.”

Fan said he combed through preprints like the CSHL-based bioRxiv and related medRxiv every day for important updates on the disease.

Fan described the scientific focus and effort of the research community as being akin to the Manhattan Project which built the atomic bomb during World War II, where “everybody said, ‘We have a common enemy and we want to apply all our capabilities to combating that.”

While Fan is pleased with the productive and valuable exchanges that occurred amid the virtual conferences, he recognized the benefit of sharing a room and a drink with scientific colleagues.

“A lot of the productive interactions at meetings take place in a social setting, at the bar, over dinner” and in other unstructured gatherings, he said. “People are relaxed and can share their scientific thoughts.”

After presentations, Fan described how researchers discuss the work presented and compare that to their own efforts. It’s easier to talk with people in person “as opposed to making a formalized approach through letters and emails.”