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Power of 3

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From left, Luisa Escobar-Hoyos, Lucia Roa and Ken Shroyer Photo by Cindy Leiton

By Daniel Dunaief

The prognosis and treatment for cancer varies, depending on the severity, stage and type of disease. With pancreatic ductal adenocarcinoma, the treatment options are often limited and the prognosis for most patients by the time doctors make a diagnosis is often bleak.

Researchers at the Renaissance School of Medicine’s Pathology Department at Stony Brook University have been testing for the presence of a protein called keratin 17, or K17, by staining tissue specimens or needle aspiration biopsy specimens. This measures the proportion of tumor cells that have high levels of expression.

This protein is typically active during embryological development or in stem cells, which are a type of cell that can differentiate into a wide range of other cells. It is also active in pancreatic cancer.

Ken Shroyer, department chairman; Luisa Escobar-Hoyos, assistant professor of pathology; and Lucia Roa, assistant professor of pathology recently published a paper in the journal Scientific Reports in which they documented how the level of this protein can indicate the prognosis for patients. K17 above a certain level typically suggests a worse prognosis.

The Stony Brook scientists want to understand why some pancreatic cancers are more aggressive than others, with the hope that they might be able to develop more effective ways to treat the most aggressive form of the disease.

In the recent research, the level of K17 not only indicated the prognosis for the most aggressive form of the disease, but it is also considered a “cause of making the tumors more aggressive,” Escobar-Hoyos added, which confirmed their previously published research and which unpublished data also supports.

Shroyer suggested that this research paper has been a validation of their plan to pursue the development of K17 as a way to differentiate one form of this insidious cancer from another.

While other cancers, such as cervical cancer, have proven quicker and easier to use K17 for its predictive power, the current work reflects the lab’s focus on pancreatic cancer. As such the research is a “great step forward to generate our first pancreatic cancer paper,” Shroyer said. His lab had previously published papers on other biomarkers in pancreatic cancer.

Escobar-Hoyos indicated that she and Shroyer anticipate that K17, which is one of a family of 54 different types of keratins in the human body, likely plays numerous roles in promoting cancer.

Indeed, K17 may promote the invasiveness of these cells, allowing them to spread from the original organ, in this case the pancreas, to other parts of the body. They are testing that concept through ongoing work in their lab.

The researchers believe that K17 may accelerate metastasis, but that line of thinking is “still at a relatively early stage,” Escobar-Hoyos said.

This protein may also change the metabolism of the cell. They believe K17 blocks the uptake of certain drugs by enhancing specific metabolic pathways. 

Additionally, K17 causes the degradation of p27, which is a tumor suppressor that controls cell division.

The researchers used two different ways to monitor the levels of protein, through mRNA analysis and through immunohistochemical localization. In the latter case, that involved staining the cells to look for the presence of the protein.

Roa, who is the first author on the paper, stained the slides and worked with Shroyer to score them.

The assistant professor, who came to Long Island with her daughter Laura who earned her bachelor’s degree and master’s in public policy at SBU, had been a pathologist and medical doctor when she lived in Colombia. She learned the IHC staining technique at Yale University just after she graduated from medical school and worked for six years as a postdoctoral fellow on several projects using IHC.

Roa is thrilled that she’s a part of a supportive team that could help develop techniques to improve patient diagnosis and care.

“We care deeply about developing a tool that will help us to treat patients and we value working together to accomplish this,” Roa explained in an email.

At this point, Shroyer and his team have identified key factors that cause K17 to be overexpressed. They are pursuing this line of research in the lab.

“We think K17 expression is dictated by something different than genetic status,” said Escobar-Hoyos. “This is speculation, but we think it might be triggered based on a patient’s immunity.”

After this study, the pathology team is looking to validate their results through different cohorts of patients. They are working with the Pancreatic Cancer Action Network and their scientific collaborators at Perthera Inc. to process tissue sections from these cases for K17 staining in their lab.

They are also at the early stages in the development of a collaboration with investigators at MD Anderson Cancer Center.

“If we can validate that K17 IHC testing is able to predict a response to the standard of care, then we’ll have permission to start a prospective analysis linked to a clinical trial,” Shroyer said.

Shroyer’s team is trying to understand how K17 becomes activated, what happens when they block that activation, and how it impacts the survival and tumor growth in animal models of pancreatic cancer.

In collaborations with other researchers, they are exploring how K17 impacts the therapeutic vulnerability of pancreatic cancer to over 2,000 FDA-approved compounds.

“There are a discrete list of compounds that are able to kill K17 positive cells,” Shroyer said. He is aiming to start phase 0 trials to validate the molecular model. If the data is sufficiently convincing, they can apply to the FDA to begin phase 1 trials.

He hopes this study is the first of many steps the lab will take in providing clues about how to diagnose and treat pancreatic cancer, which has been an intractable disease for researchers and doctors.

“This paper helps establish and confirm that K17 is an important and promising prognostic biomarker in pancreatic cancer,” Shroyer said. “For us, this is foundational for all the subsequent mechanistic studies that are in progress to understand how K17 drives cancer aggression.”

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Dr. Minsig Choi and Paul Bingham. Photo from Stony Brook Medicine

By Daniel Dunaief

The Stony Brook Cancer Center is seeking patients with pancreatic cancer for a phase 3 drug trial of a treatment developed by a husband and wife team at SBU.

Dr. Minsig Choi. Photo from Stony Brook Medicine

Led by Minsig Choi, the principal investigator of the clinical trial and a medical oncologist at Stony Brook Cancer Center’s gastroenterology team, the study is part of a multicenter effort to test whether a drug known as CPI-613, or devimistat, can extend the lives of people battling against a form of cancer that often has a survival rate of around 8 percent five years after its discovery.

Paul Bingham. Photo from Stony Brook Medicine

Patients at Stony Brook will either receive the conventional treatment of FOLFIRINOX, or a combination of a FOLFIRINOX and CPI-613. An earlier study demonstrated a median survival of 20 months with the combination of the two drugs, compared with 11 months with just the standard chemotherapy.

“Pancreatic cancer is such a bad disease,” Choi said. “The overall survival is usually less than a year and life expectancy is very limited.”

Choi said the company that is developing the treatment, Rafael Pharmaceuticals, wanted Stony Brook to be a part of the larger phase 3 study because the drug was developed at the university. Indeed, Stony Brook is the only site on Long Island that is offering this treatment to patients who meet the requirements for the study.

People who have received treatment either from Stony Brook or at other facilities are ineligible to be a part of the current trial, Choi said. Additionally, patients with other conditions, such as cardiac or lung issues, would be excluded.

Additionally, the current study is only for “advanced patients with metastatic” pancreatic cancer, he said. People who have earlier forms of this cancer usually receive surgery or other therapies.

“When you’re testing new drugs, you want to start in a more advanced” clinical condition, he added.

Choi said patients who weren’t a part of the study, however, would still have other medical options.

Zuzana Zachar. Photo from Stony Brook Medicine

“The clinical trial is not the only way to treat” pancreatic cancer, he said. These other treatments would include chemotherapy options, palliative care, radiation therapy and other supportive services through social workers.

Choi anticipates that the current study, which his mentor Philip A. Philip, a professor in the Department of Oncology at the Barbara Ann Karmanos Cancer Institute in Detroit is leading, would likely provide preliminary results in the next 18 to 24 months.

If the early results prove especially effective, the drug may receive a fast-track designation at the Food and Drug Administration. That, however, depends on the response rate and the way patients tolerate the treatment.

At this point, Choi anticipates that most of the side effects will be related to the use of chemotherapy, which causes fatigue and weakness. The CPI-613, at least in preliminary studies, has been “pretty well tolerated,” although it, like other drug regimes, can cause upset stomachs, diarrhea and nausea, he said.

Doctors and researchers cautioned that cancer remains a problematic disease and that other drugs to treat forms of cancer have failed when they reach this final stage before FDA approval, in part because cancer can and often does develop ways to work around efforts to eradicate it.

Still, the FDA wouldn’t have approved the use of this drug in this trial unless the earlier studies had shown positive results. Prior to this broader clinical effort, patients who used CPI-613 in combination with FOLFIRINOX had a tumor response rate of 61 percent, compared with about half that rate without the additional treatment.

Paul Bingham, an associate professor in the Department of Biochemistry and Cell Biology at Stony Brook University, and his wife Zuzana Zachar, a research assistant professor and director of Master in Teaching Biology Program at the Institute for STEM Education at Stony Brook, originally invented and discovered the family of drugs that includes CPI-613.

Bingham and Zachar, who are consultants to Rafael Pharmaceuticals, “provide basic scientific support” in connection with this phase 3 trial. “When the FDA asks questions, sometimes it requires us to do basic science” to offer replies, he said.

Zachar and Bingham developed this drug because they anticipated that attacking cancer cell’s metabolism could lead to an effective treatment. Cancer requires considerable energy to continue on its deadly course. This drug, which is a lipoate analog and is an enzyme cofactor in several central processes in metabolism, tricks the disease into believing that it has sufficient energy. Interrupting this energy feedback mechanism causes the cancer cell to starve to death. 

While other cells use some of the same energy feedback pathways, they don’t have the same energy demands and the introduction of the drug, which has tumor-specific effects, is rarely fatal for those cells.

The lipoate analog is a “stable version of the normally transient intermediary that lies to the regulatory systems, which causes them to shut down the metabolism of cancer cells,” Bingham said. These cells “run out of energy.”

Zachar said the process of understanding how CPI-613 could become an effective treatment occurred over the course of years and developed through an “accretion of data that starts to fill in a picture and eventually you get enough information to say that it could be” a candidate to help patients. The process is more “incremental than instantaneous.”

Bingham and Zachar are working on a series of additional research papers that reflect the way different tumors and tumor types have different sensitivities to CPI-613. They expect to publish at least one new paper this year and several more next year.

The researchers who developed this drug have had some contact with patients through the process. While they are not doctors, they are grateful that the work they’ve done has “extended and improved people’s lives,” Bingham said, and they are “grateful for that opportunity.”

Zachar added that she is “thrilled that we’ve been able to help.” She appreciates the contribution the patients make to this research because they “stepped to the line and took the risk to try this drug.”

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Anne Churchland with former postdoctoral fellow Matt Kaufman at Cold Spring Harbor Laboratory. The microscope is a 2-photon microscope and is one of three techniques used to measure neural activity in the mouse brain. Photo from Margot Bennett

By Daniel Dunaief

Fidgeting, rocking and other movements may have some benefit for thinking. Yes, all those people who shouted to “sit still” may have been preventing some people from learning in their own way.

In a new experiment conducted on mice published in the journal Nature Neuroscience this week, Anne Churchland, an associate professor at Cold Spring Harbor Laboratory, linked idiosyncratic mouse movements to performance in a set of tasks that required making decisions with rewards.

“Moving when deep in thought is a natural thing to do,” Churchland said. “It deeply engages the brain in ways that were surprising to us.”

She suggested that many people believe thinking deeply requires stillness, like the statue of The Thinker created by Auguste Rodin. “Sometimes it does, but maybe not for all individuals,” adding that these movements, which don’t seem connected to the task at hand, likely provide some benefit for cognition.

“We don’t know yet for sure what purpose these movements are serving,” she said.

Margaret Churchland with the lab group at CSHL

Mammals tend to exhibit a process called “optimal motor control.” If a person is reaching out to grab a cup, she tends to move her arm in a way that is energy conserving. Indeed, extending this to her rodent study, Churchland suggests that somehow these ticks, leg kicks or other movements provide assistance to the brain.

In theory, she suggested that these movements may be a way for the brain to recruit movement-sensitive cells to participate in the process. These brain cells that react to movement may then participate in other thought processes that are unrelated or disconnected from the actions themselves.

Churchland offers an analogy to understanding the potential benefit of these extra movements in the sports world. Baseball players have a wide range of stereotyped movements when they step up to the plate to hit. They will touch their shirt, tug on their sleeves, readjust their batting gloves, lift up their helmet or any of a range of assorted physical activities that may have no specific connection to the task of hitting a baseball.

These actions likely have “nothing to do” with the objective of a baseball hitter, but they are a “fundamental part of what it means to go up to bat,” she said.

In her research, Churchland started with adult mice who were novices at the kinds of tasks she and her colleagues Simon Musall and Matt Kaufman, who are the lead authors on the paper, trained them to do. Over a period of months, the mice went from not understanding the objective of the experiment to becoming experts. The animals learned to grab a handle to start a trial or to make licking movements.

These CSHL researchers tracked the behavior and neural activity of the mice every day.

Churchland said a few other groups have measured neural activity during learning, but that none has studied the kind of learning her lab did, which is how animals learn the structure of an environment.

The extra movements that didn’t appear to have any connection to the learned behaviors transitioned from a disorganized set of motions to an organized pattern that “probably reflected, in the animal’s mind, a fundamental part of what it means to make a decision.”

Churchland suggested that some of these conclusions may have a link to human behavior. Each animal, however, has different behaviors, so “we always need to confirm that what we learn in one species is true for another,” she wrote in an email.

Parents, teachers, coaches and guest lecturers often look at the faces of young students who are shaking their legs, rocking in their chair, twiddling their thumbs or spinning their pens between their fingers. While these actions may be distracting to others, they may also play a role in learning and cognition.

The study “suggests that allowing certain kinds of movements during learning is probably very important,” Churchland said. “When we want people to learn something, we shouldn’t force them to sit still. We should allow them to make movements they need to make which will likely help” in the learning process.

Churchland believes teachers already know that some students need to move. These educators also likely realize the tension between allowing individual students to be physically active without creating a chaotic classroom. “Most teachers are working hard to find the right balance,” she explained in an email.

She also suggested that different students may need their own level of movement to stimulate their thinking.

Some adults may have already developed ways to enhance their own thinking about decisions or problems. Indeed, people often take walks that may “finally allow those circuits you need for a decision to kick in.”

Down the road, she hopes to collaborate with other scientists who are working with nonhuman primates, such as marmosets, which are new world monkeys that live in trees and have quick, jerky movements, and macaques, which are old world monkeys and may be familiar from their island perch in an exhibit in the Central Park Zoo.

Churchland said extensions of this research could also go in numerous directions and address other questions. She is hoping to learn more about attention deficit hyperactivity disorder and the brain.

“We don’t know when that strategy [of using movement to trigger or enhance thinking] interferes with the goal,” she said. “Maybe the movements are a symptom of the learner trying to engage, but not being able to do so.”

Ultimately, Churchland expects that different pathways may support different aspects of decision making, some of which can and likely are connected to movement.

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Viviana Cavaliere. Photo courtesy of BNL

By Daniel Dunaief

The United States has been the site of important life events for Italian-born Viviana Cavaliere. When she was in high school, she went to Montana, where she changed her mind about her life — she had wanted to become an architect — and decided that science was her calling.

Later, when she did a summer student program at Fermilab near Chicago, she met her future husband Angelo Di Canto, who is also a physicist.

While Cavaliere has been an assistant physicist at Brookhaven National Laboratory since 2017, she has been living in Switzerland, where she has been working at CERN. She is preparing for a move this month to Long Island, where she hopes to find new physics phenomena, including new particles, using the Atlas detector at the Large Hadron Collider at CERN.

Viviana Cavaliere during a trip to Bhutan. Photo by Angelo Di Canto

Cavaliere will return to the United States with a vote of confidence in her potential and some financial support. The Department of Energy recently announced that she was the recipient of $2.5 million over five years as a part of the Office of Science’s Early Career Research Program.

“I am very honored,” said Cavaliere, who will use the funds to support the research of postdoctoral scientists in her lab, to buy equipment and to travel to conferences and to CERN.

At the heart of her research is a desire to search for new particles and new phenomena that might build on the Standard Model of particle physics.

Cavaliere is coordinating a group of about 400 physicists who are looking for new particles. Her role is to analyze the data from the Large Hadron Collider.

Indeed, officials at the Department of Energy said that Cavaliere was one of only three recipients in the Energy Frontier Program from a pool of 23 applicants because of her role at CERN.

The award “requires those who have shown leadership capability,” said Abid Patwa, program manager for the Energy Frontier Program and special assistant for International Programs in the DOE Office of High Energy Physics. Cavaliere has “already been participating and leading” studies.

Michael Cooke, who is a program manager in the Office of High Energy Physics in the Department of Energy’s Office of Science, said Cavaliere’s work fits the description of a “high risk and high reward” proposal that could “steer the field in new directions.”

By using new software, Cavaliere will mine data produced in a microsecond, which is 10 to the negative sixth of a second, for ways to filter specific events.

Patwa suggested that his office urges principal investigators to be as “quantitative as possible” in their work, so that they can show how their efforts will be successful.

Viviana Cavaliere during a trip to Macchu Picchu. Photo by Angelo Di Canto

Cavaliere is not only conducting scientific research but is also part of the technological innovations.

“It helps a person’s career that they understand all aspects of what is involved in running these major experiments,” Patwa said.

Collaborators are encouraged to have balanced roles in research and hardware operations or upgrade activities, Patwa explained in an email.

Cavaliere was at CERN when the elusive Higgs boson particle was discovered in 2012. The particle, which is called the “God” particle, had been proposed 48 years earlier. The Higgs boson explains why particles have mass.

“It was a very exciting day, you could feel the joy in the corridors and I believe it was one of those days where nobody could concentrate on work waiting for the official release of the news,” Cavaliere recalled. “At the time, I thought it would be great if we had more days like those, with the excitement of the discovery.”

Cooke said that extending the work from the Higgs boson could offer promising new clues about physics. He described how Cavaliere is making high precision measurements of particle interactions involving the Higgs boson. Any discrepancy between what she finds and the predictions of the Standard Model could be a hint of new particles, he explained in an email.

“Not only will her analysis advance the field by improving the search for new physics, but the new tools she creates to capture the best data from the [Large Hadron Collider] will be applicable much more broadly,” Cooke said.

Patwa, who worked at BNL as a postdoctoral research associate and then as a staff scientist from 2002 to 2012, explained that he is “encouraged by the talented researchers joining BNL as well as other DOE national laboratories and universities.” He believes the award is a testament to her past accomplishments and to her current objectives.

When she was growing up in a town near Naples in southern Italy, Cavaliere had to choose whether to attend a classical high school or a school focused on math and physics. Particularly interested in history, she decided to study at a classical school.

During her senior year of high school, she traveled on an exchange program to Montana, where she did experiments in the lab with a “very, very good teacher. I started liking science and was undecided between chemistry and physics.”

The travel experience to the Big Sky state “opened my mind, not only about what you do in the future, but also gives you a taste of a different culture.”

When she attended the Sapienza University of Rome, she had to catch up to her colleagues, most of whom had learned more math and physics than she. It took a year and a half to reach the same point, but she graduated with her class.

When she did her postdoctoral work in Chicago, she met Di Canto, who grew up about 100 kilometers away from her in Italy as well. “My mom always makes fun of me,” Cavaliere said, because she “found her husband in the United States.”

As for work, she is inspired to use the funds and the recognition from the DOE to build on her developing career.

“There’s always some hope you’ll find something new,” she said.

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Above, Kevin Reed at a presentation at the Montauk Lighthouse in July. Photo from Kevin Reed

By Daniel Dunaief

Hurricane Dorian has dominated the news cycle for weeks, as its violent winds, torrential rains and storm surge caused extensive damage throughout the Bahamas and brought flooding and tornadoes to North Carolina.

For Kevin Reed, an assistant professor at Stony Brook University’s School of Marine and Atmospheric Sciences who models extreme weather events including hurricanes, Dorian followed patterns the climate scientist anticipates will continue to develop in future years.

“Two things that are current with Dorian are consistent with what we’d expect from a changing climate,” said Reed. Dorian became a Category 5 storm, which is the strongest on the Saffir-Simpson Hurricane Wind Scale. Second, the hurricane slowed down, which was also a trend that Hurricanes Harvey and Florence demonstrated.

The reason a warming climate would slow a hurricane like Dorian is that the polar regions are warming more rapidly than the tropics. That can have a “huge impact on the overall circulation” within the atmosphere, Reed said.

Indeed, what controls the speed of the jet stream, which moves hurricanes and other storm systems along over the rotating planet, is the difference in the temperature between the tropics and the poles. When the poles warm up more rapidly than the tropics, the circulation in the atmosphere can slow down and that can reduce the speed of the wind that blows the hurricane.

“Hurricanes are impacted by climate” and any change in that dynamic will have an effect on storms that can and do present a threat to the homes, businesses and lives of people in their path, Reed said.

Basic research has enhanced and improved the ability of forecasters to predict where a storm like Dorian will go, allowing meteorologists and the National Hurricane Center to provide warnings to political leaders and emergency response teams.

“Our general understanding of why storms move and go where they do has improved significantly over the last few decades,” Reed said. “Part of that can be seen in the forecast.”

Most of these forecasts are informed by numerical models. That is where Reed brings his expertise to hurricane science.

“I am a numerical modeler,” he said. “I use and help develop models to understand tropical cyclones and precipitation in general.”

Using information often taken from satellites, from in situ observations, radar along the coastlines and aircraft that fly every few hours into a storm, especially when they threaten the Caribbean or the East Coast, forecasters have had a “steady improvement in these models.”

Reed likens the process of predicting the weather or tracking a hurricane to choosing a stock. As investors and companies have become more sophisticated in the way they analyze the market or individual companies, their algorithms improve.

Investors have “added more variables” to choose companies for their investments, while forecasters have added more information from enhanced observations.

As for the ongoing coverage of hurricanes, Reed said the general population seems to have a relatively good awareness of the path and destructive power of the storms. The one area, however, that may help people focus on the potential danger from a storm comes from the way people describe these hurricanes.

Often, media outlets focus on the speed on the wind. While the wind can and does topple trees, causes property damage and disrupts power supplies, much of the damage comes from the storm surge. Rising water levels, however, is often the reason state and national officials encourage people to evacuate from their homes.

“Whether a storm is a Category 2 or a Category 3 doesn’t take into account the size of the storm,” Reed said. Hurricanes can range in size fairly dramatically. Hurricane Sandy was not even a hurricane when it made landfall, but it was so big and it impacted a much wider area that it had a much larger storm surge.

After a storm blows off into the ocean or dissipates, the scientific community then spends considerable time learning the lessons from the storm.

In the case of Dorian, researchers will explore why models initially predicted a landfall in Florida as a Category 4 storm. They will look at what happened to slow it down, which will inform future versions of forecasts for other storms.

In the future, Reed hopes researchers enhance their ability to represent convective processes in the models. These involve the formation of clouds and rain, especially in the context of a storm.

“That’s something that’s constantly been a difficulty,” he said. “It’s a complex process. While we have theories to understand it, we are always improving our ways to model it.”

In the next 10 years, researchers will move past the point of trying to estimate convection and will get to the point where they run models that explicitly resolve convection, which eliminates the need to estimate it.

Reed believes investing in fundamental research is “crucial. The return on investment to society and to the country is one of the best investments you can make. We have shown that through a steady improvement in the hurricane track,” which came about because of fundamental research. “The only way to continue that improvement is through basic and applied research that leads to these outcomes.”

A native of Waterford, Michigan, which is about 45 minutes away from Detroit, Reed didn’t have any firsthand experiences with hurricanes when he was growing up. Rather than watching MTV the way his friends did, he would watch hurricane updates or tropical storm updates.

A resident of Queens, Reed enjoys traveling and has a self-described “unhealthy” commitment to the University of Michigan football team. He purchases season tickets each year and takes 6 a.m. flights from LaGuardia to Michigan, where an Uber brings him to his fellow tailgaters before home games.

As for future hurricanes, Reed said the current consensus is that they will be lower in number but higher in intensity. Hurricane forecasts expect “more intense precipitation, but less frequent” storms, he said.

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In foreground, from left, senior scientist Paul O’Connor holding an electronic board, and Science Raft Subsystem manager Bill Wahl holding a mock raft assembly. Behind O’Connor, on the left, is Sean Robinson, a technical associate, who is working on a raft in the clean room, and to the left is mechanical engineer Connor Miraval, whose image is reflected on the focal plane. Photo from BNL

By Daniel Dunaief

What’s out there? It’s a question that occurs to everyone from parents sleeping at night who hear a noise in the front yard to tourists aboard a whale watching cruise off the coast of Montauk to anyone looking up at the night sky.

Scientists at Brookhaven National Laboratory recently took a milestone step in a long journey to understanding objects and forces deep in space when they completed shipment of the last of 21 rafts that will become a part of the Large Synoptic Survey Telescope, or LSST, in the Cerro Pachón ridge in north central Chile.

The rafts will serve as the film in a camera that will take images that cover 40 times the area of the moon in a single exposure.

The telescope, which will be the world’s largest digital camera for astronomy, will allow researchers and the general public to view asteroids at great distances. It will also provide information about dark energy and dark matter, changes in the night sky over the course of a decade of collecting data, and data that can build on knowledge about the formation and structure of the Milky Way.

Paul O’Connor, a senior scientist at BNL’s Instrumentation Division who has worked on the LSST for 17 years, expressed appreciation for the efforts of people ranging from area high schoolers to senior scientists on the project.

“It was just a joy to see the dedication from everyone to get what needed to be done,” he said in an email. “It takes a team like that to complete a project like this.”

The LSST, which is funded in part by the National Science Foundation and the Department of Energy, involves researchers from institutions all over the world who have each played a role in moving the unique telescope toward completion.

While the rafts that will function as the film for the 3.2-gigapixel sensor array are completed, O’Connor will continue to work on commissioning the telescope, which should occur gradually until it begins providing data in October of 2022.

O’Connor said the construction of the 21 raft modules containing a total of 200 16-megapixel sensors involved “moments of drama, both good and bad.”

The first time the team brought the system into its operating temperature range of about 100 degrees below zero Celsius, some of the cool-down behavior “differed from our predictions,” he explained.

That required quick thinking to make sure the equipment wasn’t damaged. This was especially important not only because the operation needed to stay on schedule but also because the rafts are expensive and the team was operating on a budget. “Each of these rafts has an enormous cash value” and involved considerable labor to build, O’Connor added.

Bill Wahl, the science raft subsystem manager of the LSST project since 2015, described how one of the challenges involved packing and shipping such sensitive electronic materials.

“We came up with a very elegant and somewhat low-cost approach,” he said, which involved shipping these rafts in a pressurized vessel that avoided damage during any shocks in transit.

The rafts, which each weighs about 25 pounds, had a shipping weight that included protective fixtures of over 100 pounds.

Additionally, the BNL team had to deal with cleanliness, as particulates can and did cause problems. Some of the rafts didn’t function the way they should have after shipping. The BNL team went through a complete refurbishing over six months, where they took all the rafts apart and cleaned them. They upgraded the design to limit the amount of particulates, Wahl said.

While BNL built the requisite rafts, it has an additional two rafts that can replace any of those in the telescope if necessary.

These extra rafts will be stored at the observatory.

Along with the challenges and some anxiety from building such sensitive equipment, the instrumentation unit also had several high points.

In January of 2017, BNL tested one of the rafts in the clean room. Scientists constructed an image projector and projected that onto the raft with enough detail to show that every pixel was functioning correctly. O’Connor made a printout of that image and taped it to his office door.

The day of the successful test was one that the team had been anticipating for “over 10 years. When the first image was delivered, it was very gratifying to see the system was working,” he said.

While O’Connor isn’t a cosmologist, he is particularly interested in the search for dark energy. “It has been puzzling the theorists and as experimentalists, we hope to take measurements that will one day lead to a resolution of this fundamental question,” he explained.

Several teams are working on the LSST in different locations. One of them is constructing the telescope in Chile, while another is assembling the camera in California.

At this point, technicians have installed about half the rafts into the main camera cryostat. Researchers will conduct a preliminary test before populating the rest of the focal plane with all the rafts later this year, O’Connor explained.

As the LSST catalogues four billion galaxies, it will “literally be impossible” to look at these areas item by item. Informatics tools will be necessary to extract all the information, O’Connor said.

Wahl suggested that the LSST could become an important educational tool for budding astronomers.

“I’m not an astronomer or physicist,” said Wahl, who will become the chief operating officer of an instrumentation group at BNL on Oct. 1, “but from my point of view, what I find absolutely amazing is that everyone relies heavily on Google Earth to look at where they are going. In a similar way, [people] are going to do that in the sky. It’s going to give them the opportunity to be junior astronomers unlike they’ve ever been able to do.”

Indeed, the LSST will help people figure out what’s out there.

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Above, Leila Esmailzada, executive director of BeLocal observes a traditional charcoal making process in Madagascar. Photo from BeLocal

By Daniel Dunaief

BeLocal has progressed from the drawing board to the kitchen. The nonprofit group, which was started by the husband and wife team of Mickie and Jeff Nagel as well as data scientist Eric Bergerson, has been working to improve and enhance the lives of people living in Madagascar.

BeLocal, which started in 2016, has sent representatives, including Laurel Hollow resident Mickie Nagel and executive director Leila Esmailzada, to travel back and forth to the island nation off the southeast coast of the African continent.

Working with Stony Brook University students who identified and tried to come up with solutions for local challenges, BeLocal has focused its efforts on creating briquettes that use biomass instead of the current charcoal and hardwood, which not only produces smoke in Malagasy homes but also comes from cutting down trees necessary for the habitat and the wildlife it supports.

Biochar briquettes reduce the amount of hardwood Malagasy residents chop down to provide fuel for cooking. Photo from BeLocal

“In the summer of 2018 we figured out that we had something that works,” said Mickie Nagel. “We had all the agricultural waste and could turn it into fuel. Our goal is to start thinking about how to bring it into communities and into the daily lives” of people in Madagascar.

In January of this year, Esmailzada partnered up with Zee Rossi to introduce the new briquettes to residents of three villages, who were interested in the BeLocal process and offered feedback.

Rossi worked in Madagascar for three years as a part of the Agricultural Food Security Advisory Section of the Peace Corps, until he recently joined the staff at BeLocal.

At this point, BeLocal has helped create four working production sites for the briquettes, all of which are on the outskirts of the Ranomofana National Park, which Stony Brook Professor Patricia Wright helped inaugurate in 1991.

The biochar briquettes solve several problems simultaneously. For starters, they reduce the amount of hardwood Malagasy residents chop down to provide fuel for cooking. The biochar briquettes are made from agricultural waste, such as corn husks and cobs, rice stalks, leaves, small sticks and even unusable waste from the production of traditional charcoal.

The briquettes also produce less smoke in the homes of the Malagasy. At this point, BeLocal doesn’t have any data to compare the particulates in the air from the briquettes.

One of the current briquette makers is generating about 2,000 of the circular fuel cells per month. As a start-up effort, this could help with several families in the villages. Nagel estimates that it takes about 12 briquettes to cook a meal for a family of four. The families need to learn how to stoke the briquettes, which are slightly different from the cooking process with the charcoal and hardwood.

Esmailzada and Rossi had planned to return to Madagascar in July, where they hoped to understand how people are using these sources of energy.

Esmailzada has taught and workshopped with the Malagasy on how to make the briquettes. Since returning to the United States, where she recently completed a master’s program in public health with a focus on community health at Stony Brook University, she was eager to see how much progress has been made.

BeLocal has continued to refine the technique for creating these briquettes. Working across the border with Stony Brook graduate student Rob Myrick, Malagasy residents have tried to char the biomass in a barrel, instead of digging a pit.

“Hopefully there will be movement” with the barrel design, Nagel said.

Myrick is working on refining the airflow through the pit, which could enhance the briquette manufacturing process.

Myrick will “work on techniques [at Stony Brook] and [Rossi] will work on the process with the villagers over there,” Nagel explained in an email. Myrick has been “such a helpful and great addition to BeLocal.”

Esmailzada and Nagel are delighted that Rossi joined the BeLocal effort.

“It’s such a natural partnership,” Esmailzada said. “He built this incredible trust with this group of really dynamic people. Having him be the liaison between us and the community really came together nicely.”

Rossi explained some of the challenges in developing a collaboration that works for the Malagasy. “One of the biggest barriers is being a foreigner,” he said. “With any new thing you present to a farmer, you have to sell yourself first. It’s really important that you connect with a farmer on a person-to-person level.”

Numerous farmers are skeptical of the ongoing commitment foreign groups will have. Many of them have experience with a foreigner or a local nongovernmental organization coming in, doing a program and “not following up,” Rossi added.

Nagel is putting together a nongovernmental organization conference to get the organizations “working on projects in the same room,” she said.

Through this effort, BeLocal hopes to create new partnerships. The organization continues to work with Stony Brook’s VIP program, which stands for vertically integrated projects.

Students from sophomore year through graduate school can continue to work on the same projects. The goal is to enable a continued commitment, which the school hopes will lead to concrete results, instead of one-year efforts that often run into obstacles that are difficult to surmount in a short period of time.

Ultimately, Nagel believes the process of building briquettes could translate to other cross-border efforts and suggested that these goals should include the kind of information crowd-sourcing that benefits from other successful projects.

BeLocal is receptive to support from Long Islanders and elsewhere.

Nagel added that projects like the briquette effort keep the context and big picture in mind.

“Helping Patricia Wright save this rain forest and the lemurs will always be a goal and we know the only way to do that is to help with alternatives to food and fuel sources, and better farming techniques so they don’t have a need to slash and burn more rain forest to add more farming fields,” Nagel said.

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Peter Van Nieuwenhuizen

By Daniel Dunaief

Peter van Nieuwenhuizen was sitting at the kitchen table, paying an expensive dental bill, when he received an extraordinary phone call. After he finished the conversation, he shared the exciting news — he and his collaborators had won a Special Breakthrough Prize in Fundamental Physics for work they’d done decades earlier — with his wife, Marie de Crombrugghe.

The prize, which is among the most prestigious in science, includes a $3 million award, which he will split with Dan Freedman, a retired professor from the Massachusetts Institute of Technology and Stanford University, and Sergio Ferrara from CERN.

De Crombrugghe suggested he could use the money “for a whole new set of teeth,” if he chose.

Van Nieuwenhuizen, Freedman and Ferrara wrote a paper in 1976 that extended the work another famous physicist, Albert Einstein, had done. Einstein’s work in his theory of general relativity was incomplete in dealing with gravity.

Freedman, who was at Stony Brook University at the time, van Nieuwenhuizen and Ferrara tackled the math that would provide a theoretical framework to include a quantum theory of gravity, creating a field called supergravity.

From left, Peter van Nieuwenhuizen, Sergio Ferrara, and Dan Freedman in 1980.

After 43 years, “I didn’t expect” the prize at all, said van Nieuwenhuizen. It’s not only the financial reward but the “recognition in the field” that has been so satisfying to the physicist, who continues to teach as a Toll Professor in the Department of Physics at SBU at the age of 80.

“To have one’s work validated by great leaders has just been wonderful,” added Freedman, who worked at SBU through the 1980s until he left to join MIT. He treasures his years at Stony Brook.

Freedman believes a seminal trip to Paris, where he discussed formative ideas that led to supergravity with Ferrara, was possible because of Stony Brook’s support.

The physics trio approached the problem of constructing a way to account for gravity by combining general relativity and particle physics, which were in two separate scientific communities at the time. Even the conferences between the two types of physics were separate.

Einstein’s theory of general relativity has infinities when scientists add quantum aspects to it. As a result, it becomes an inconsistent theory. “Supergravity is not a replacement of Einstein’s theory, it is an extension or a completion if one is bold,” van Nieuwenhuizen explained.

The Stony Brook professor suggested that supergravity is an extension of general relativity just as complex numbers are an extension of real numbers. He added that it’s unlikely that there are other extensions of general relativity that theoretical physicists have yet to postulate.

Supergravity is “confirmed by its finiteness,” he said, adding that it suggests the existence of a gravitino, which is a partner to the graviton or the gravity-carrying boson. At this point, scientists haven’t found the gravitino.

“Enormous groups have been looking” for the gravitino, but, so far, “haven’t found a single one,” van Nieuwenhuizen said. The search for such a particle isn’t a “problem for me. That’s what experimental physicists must solve,” he said.

The work has already had implications for numerous other fields, including superstring theory, which attempts to provide a unified field theory to explain the interactions or mechanics of objects. Even if the search for a gravitino doesn’t produce such a particle, van Nieuwenhuizen suggested that supergravity still remains a “tool able to solve problems in physics and mathematics.”

Indeed, since the original publication about supergravity, over 11,000 articles have supergravity as a subject.

Collaborators and fellow physicists have reached out to congratulate the trio on winning the Special Breakthrough Prize, which counts the late Stephen Hawking among its previous winners.

The theoretical impact of supergravity “was huge,” said Martin Roček, a professor in the Department of Physics at Stony Brook who has known and worked with van Nieuwenhuizen for decades.

Whenever interest in the field wanes, Roček said, someone makes a new discovery that shows that supergravity is “at the center of many things.”

He added that the researchers are “very much deserving” of the award because the theory “offers such a rich framework for formulating and solving problems.”

Roček, who worked as a postdoctoral researcher in Hawking’s laboratory, said other researchers at Stony Brook are “all delighted” and they “hope some of the luster rubs off.”

Van Nieuwenhuizen’s legacy, which is intricately linked with supergravity, extends to the classroom, where he has invested considerable time in teaching.

Van Nieuwenhuizen is a “wonderful teacher,” Roček said. Indeed, he received the Dean’s Award for Excellence in Graduate Teaching in 2010 based on teaching evaluations from graduate students. Roček has marveled at the way van Nieuwenhuizen prepares for his lectures, adding, “He doesn’t give deep statements and leave you bewildered. He explains things explicitly and he does a lot of calculations without being dull.”

Van Nieuwenhuizen recalled the exhilaration, and challenge, that came from publishing their paper in 1976. “We knew right away” that this was a seminal paper, he said. “The race was on to discover its consequences.”

Prior to the theory, the three could work in relative calm before the physics world followed up with more research. After their discovery, they knew the “happy, isolated life is over,” he said..

Van Nieuwenhuizen has no intention to retire from the field, despite the sudden funds from the prize, which is sponsored by Sergey Brin, Priscilla Chan, Mark Zuckerberg, Pony Ma, Yuri and Julia Milner and Anne Wojcicki.

“The idea that I would stop abhors me,” he said. “I wouldn’t know what on earth I would be doing. I consider it a privilege to give these courses, to work and be paid to do my hobby. It’s really unheard of.”

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A. Laurie Shroyer File photo

By Daniel Dunaief

Annie Laurie Shroyer isn’t standing on a podium somewhere, listening to the national anthem with tears in her eyes and a hand over her heart as she mouths familiar words. She hasn’t won a Nobel Prize or some other distinction that will add to a medal count or that will rise to the top of her resume.

Shroyer is, however, standing tall in an arena that matters to her and to her colleagues, mentors and collaborators.

A professor and vice chair for research in the Department of Surgery at the Stony Brook Renaissance School of Medicine and the without compensation health science officer in the Research and Development Office at the Northport VA Medical Center, Shroyer recently learned that two of her research papers on coronary artery bypass surgery made an impressive and important list.

Her papers were ranked 8th and 28th among a review by the Journal of Cardiac Surgery of the top 11,500 papers in her field, making Shroyer one of only two senior investigators in the world with two citations in the top 50.

Researchers often work in obscurity, toiling in a lab or on a computer late into the night, analyzing data, applying for grants and receiving constructive but sometimes critical comments from peer reviewers. What many of them hope for, apart from the stability of tenure or the opportunity to provide a breakthrough discovery that alters the way other researchers or clinicians think about a disease or condition, is to make a lasting impact with their work.

In many ways, this ranking suggests that Shroyer has accomplished that with research into a surgical procedure that is increasingly common.

Shroyer is “one of the most influential cardiovascular researchers of our era,” Faisal Bakaeen, the staff surgeon and professor of surgery at the Heart and Vascular Institute in Cleveland, Ohio, explained in an email. Shroyer’s leadership in her research is “proof of her deep intellect and genius.”

Learning that her research, which Shroyer explained was interdisciplinary, collaborative and team-based, was among the most cited in the field was “really an honor,” she said. “I was very pleasantly surprised.”

Shroyer heard about the distinction from the VA Hospital, which noticed her prominent place in the realm of coronary artery bypass surgery research. She conducted one of her studies, called the ROOBY trial for Randomized On/Off Bypass, through the Northport hospital.

That research, which was published in the New England Journal of Medicine and benefited from the support of the VA Cooperative Studies Program Coordinating Center and the Research and Development Offices at the Northport and Denver VA Medical centers, compared the short-term and intermediate outcomes evaluating the impact of using a heart-lung machine versus operating on a beating heart.

That trial asked focused research questions about the comparative benefits of using the machine.

Shroyer concluded that there was “no off pump advantage” across a diversity of clinical outcomes and likened the process of performing this surgery without a pump to sewing a patch onto blue jeans while a child is walking up the stairs, making the stitching process more technically demanding.

Shroyer recognizes that some doctors prefer to do the procedure without the pump. Many of them suggest they have the surgical expertise to make the process a viable one for patients.Some patients may also have specific reasons to consider off pump procedures.

As for the second highly cited paper, Shroyer worked with the STS National Adult Cardiac Surgery Database Committee team and published that in the Annals of Thoracic Surgery. That paper identified the most important preoperative risk factors associated with major morbidities after surgery.

“This paper described a broad-based analytical approach which was originally developed in the VA” by Drs. Karl Hammermeister, Fred Grover, Guillermo Marshall and Shroyer working together, she explained in an email. Given that the Society of Thoracic Surgery’s database has subsequently been used to address other research questions, this early statistical modeling approach has attracted considerable interest.

In terms of the overall list, Shroyer expressed a few surprises. For starters, she noticed a larger than anticipated proportion of articles focused on the surgical procedure’s clinical outcomes. In her view, the topic is important, but not to the exclusion of research focused on evaluating the process of care and the structures of care. These include actions that care providers take on behalf of their patients, the actions patients take for themselves, and the nature of the environment where patients seek out care.

“Identifying the adverse outcomes post-CABG informs you that there is a problem, but clinical outcomes research doesn’t provide guidance on how to solve” the problem or problems identified, she said, adding that she hopes future research evaluates the processes and structures of care that may affect risk-adjusted clinical outcomes.

Shroyer also expected that the findings of several trials published in the New England Journal of Medicine would have ended the debate about off-pump versus on-pump benefits. The debate, however, is “still active,” she said.

Five years from now, Shroyer anticipates changes in the list. She hopes these high impact journals will include evaluations of novel treatments and surgeon-based characteristics, which may influence risk-adjusted outcomes.

Shroyer is pleased with the collaborators who have worked with her, as well as with the information from which she has drawn her conclusions.

“This high level of citation represents a tribute to the entire VA ROOBY trial team as well as to the STS Adult Cardiac Surgery Database and National Database Committees’ members,” she said. “In addition to terrific collaborators, I feel very blessed to have had several great mentors,” which includes Gerald McDonald and Fred Grover.

She also appreciates that she has had appointments at Stony Brook and at the Northport VA Medical Center that support her research projects.

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By Daniel Dunaief

Screws can’t be the best and only answer. That was the conclusion neurosurgeon Daniel Birk at the Stony Brook Neurosciences Institute came to when he was reconsidering the state-of-the-art treatment for spinal injuries. The screws, which hold the spine in place, create problems for patients in part because they aren’t as flexible as bone.

That’s where Stony Brook University’s College of Engineering and Applied Sciences, headed by Fotis Sotiropoulos, plans to pitch in. Working with Kenneth Kaushansky, dean of Stony Brook University’s Renaissance School of Medicine, the two Stony Brook leaders have been immersed in uniting their two disciplines to find ways engineers can improve medical care.

Fotis Sotiropoulos

The two departments have created the Institute for Engineering-Driven Medicine, which will address a wide range of medical challenges that might have engineering solutions. The institute will focus on developing organs for transplantation, neurobiological challenges and cancer diagnostics.

The institute, which already taps into the medical and engineering expertise of both departments, will move into a new $75 million building at the Research and Development Park, in 2023.

The original investment from New York State’s Economic Development Council was for an advanced computing center. The state, however, had given Buffalo the same funds for a similar facility, which meant that former Stony Brook President Sam Stanley, who recently became the president of Michigan State University, needed to develop another plan.

Sotiropoulos and Kaushansky had already created a white paper that coupled engineering and medicine. They developed a proposal that the state agreed to fund. In return for their investment, the state is looking for the development of economic activity, with spin-off companies, jobs, new industries and new ideas, Kaushansky said.

The two leaders are developing “a number of new faculty recruits to flesh out the programs that are going in the building,” Kaushansky added.

Sotiropoulos, who has conducted research in the past on blood flow dynamics in prosthetic heart valves, believes in the potential of this collaboration. “This convergence of engineering and medicine is already doing what it was intended to do,” he said. Clinicians can get “crazy sci-fi ideas, talk to engineers and figure out a way to make it happen.”

In addition to spinal cord support, researchers in engineering and medicine are working on developing algorithms to make decisions about surgical interventions, such as cesarean sections. 

A recent project from principal investigator Professor Petar Djurić, chair of SBU’s Department of Electrical and Computer Engineering, and Gerald Quirk, an obstetrician and gynecologist at Stony Brook Medicine, recently received $3.2 million from the National Institutes of Health. The goal of the project is to use computer science to assist with the decisions doctors face during childbirth. A potential reduction in C sections could lower medical costs. 

“This is a fantastic example of this type of convergence of engineering and medicine,” said Sotiropoulos.”

Dr. Kenneth Kaushansky. Photo from SBU

While the building will host scientists across a broad spectrum of backgrounds, researchers at Stony Brook will be able to remain in their current labs and coordinate with this initiative. Combining all these skills will allow researchers to apply for more grants and, Stony Brook hopes, secure greater funding.

“For a number of years now, the [National Institutes of Health have] really favored interdisciplinary approaches to important medical problems,” Kaushansky said. “Science is becoming a team sport. The broader range of skills on your team, the more likely you’ll be successful. That’s the underlying premise behind this.”

The notion of combining medicine and engineering, while growing as an initiative at Stony Brook, isn’t unique; more than a dozen institutions in the country have similar such collaborations in place.

“We’re relatively early in the game of taking this much more holistic approach,” said Kaushansky, who saw one of the earlier efforts of this convergence when he was at the University of California at San Diego, where he worked with the Founding Chair of the Department of Bioengineering Shu Chien. 

The Stony Brook institute has created partnerships with other organizations, including Albert Einstein College of Medicine and Montefiore Medical Center.

“The more clinical people we engage, the better it is for the institute,” Sotiropoulos said.

As for the bionic spine, Kaushansky has familial experience with spinal injuries. His mother suffered through several spinal surgeries. “There’s a need for much, much better mechanical weight-bearing device that will help people with back problems,” he said.

At this point, Stony Brook has gone two-thirds of the way through the National Science Foundation process to receive a $10 million grant for this spinal cord research. Sotiropoulos suggested that a bionic spine could be “a game changer.”

While the institute will seek ways to create viable medical devices, diagnostics and even organs, it will also meet the educational mandate of the school, helping to train the next generation of undergraduate and graduate students. The school already has a program called Vertically Integrated Projects, or VIPs, in place, which offers students experiential learning over the course of three or four years. The effort combines undergraduates with graduates and faculty members to work on innovative efforts.

“These projects are interdisciplinary and are all technology focused,” Sotiropoulos said. “We bring together students” from areas like engineering, computer science and medicine, which “go after big questions,” and that the VIP efforts are structured to unite engineers and doctors-in-training through the educational process.

Through the institute, Stony Brook also plans to collaborate with other Long Island research teams at Cold Spring Harbor Laboratory and Brookhaven National Laboratory, Sotiropoulos said, adding that the scientists are “not just interested in doing blue sky research. We are interested in developing services, algorithms, practices, whatever it is, that can improve patient care and costs.”

Indeed, given the translational element to the work, the institute is encouraging a connection with economic development efforts at Stony Brook, which will enable faculty to create spin-off companies and protect their ideas. The institute’s leadership would like to encourage the faculty to “create companies to market and take to market new products and developments,” said Sotiropoulos.

Photos from SBU

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