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At the ribbon cutting of the Kavita and Lalit Bahl Center for Metabolomics and Imaging last December, from left, Lina Obeid; Yusuf Hannun; Kavita and Lalit Bahl; Samuel Stanley, President of Stony Brook University; and Kenneth Kaushansky, dean of Stony Brook University’s School of Medicine. Photo from SBU

By Daniel Dunaief

Many ways to kill cancer involve tapping into a cell’s own termination system. With several cancers, however, the treatment only works until it becomes resistant to the therapy, bringing back a life-threatening disease.

Collaborating with researchers at several other institutions, Dr. Lina Obeid, the director of research at Stony Brook University School of Medicine, has uncovered a way that cancer hides a cell-destroying lipid called ceramide from treatments. The ceramide “gets co-opted by fatty acids for a different species of fats, namely acylceramide, and gets stored side by side with the usual triglycerides,” Obeid explained in an email about her recent finding, which was published in the journal Cell Metabolism. “It makes the ceramide inaccessible and hence the novelty.” The ceramide gets stored as a lipid drop in the cell.

“We describe a completely new metabolic pathway and role in cell biology,” Obeid said. Other researchers suggested that this finding could be important in the battle against cancer. “That acylceramides are formed and deposited in lipid droplets is an amazing finding,” George Carman, the director of the Rutgers Center for Lipid Research, explained in an email. “By modifying the ceramide molecule with an acyl group for its deposit in a lipid droplet takes ceramide out of action and, thus, ineffective as an agent to cause death of cancer cells.”

Carman said Obeid, whom he has known for several years, visited his campus in New Jersey to share her results. “All of us at Rutgers were so excited to hear her story because we knew how important this discovery is to the field of lipid droplet biology as well as to cancer biology,” he said. Obeid conducted some of the work at the Kavita and Lalit Bahl Center for Metabolomics and Imaging at Stony Brook University. The center officially opened on Dec. 1 of last year on the 15th floor of the Health Sciences Center and will move to the Medical and Research Translation Building when it is completed next year. “This study is exactly the kind of major questions we are addressing in the center that [the Bahls] have generously made possible,” she explained.

Obeid discovered three proteins that are involved in this metabolic pathway: a ceramide synthesizing protein called CerS, a fatty acyl-CoA synthetase protein called ACSL and an enzyme that puts them together, called DGAT2, which is also used in fatty triglyceride synthesis. Her research team, which includes scientists from Columbia University, Northrop Veterans Affairs Medical Center and Mansoura University in Egypt is looking into implications for the role of this novel pathway as a target for cancer and obesity.

Indeed, obesity enables more frequent conversion of ceramide into acylceramide. “Fats in cells and in diets increase and predispose to obesity,” Obeid suggested. “This new pathway we found occurs when fatty acids are fed to cells or as high-fat diets are fed to mice.” In theory, this could explain why obesity may predispose people to cancer or make cancer resistance more prevalent for some people. According to Obeid, a high-fat diet can cause this collection of proteins to form in the liver of mice, and she would like to explore the same pathways in humans. Before she can begin any such studies, however, she would need numerous approvals from institutional review boards, among others.

Obeid and her collaborators hypothesize that a lower-fat diet could reduce the likelihood that this lipid would be able to evade cancer therapies.

These kinds of studies “provide the justification for looking at the effect of diet on acylceramide production,” Daniel Raben, a professor of biological chemistry at Johns Hopkins University School of Medicine, explained in an email. Further research could include “isocaloric studies with [high-fat diets] and [low-fat diets] in animals that are age and gender matched.”

Obeid was a part of the first group to describe the lipid’s role in cancer cell death in 1993. “We have been studying its metabolism and looking at how it’s made and broken down,” she said. “We found recently that it associates with these proteins to metabolize it.”

While the lipid provides a way to tackle cancer’s resistance to chemotherapy, it also has other functions in cells, including as a membrane permeability barrier and in skin. A therapy that reduced acylceramide could affect these other areas but “as with hair loss [with chemotherapy treatment], this will likely be easily managed and reversible,” Raben explained.

Obeid and Yusuf Hannun, the director of the Cancer Center at Stony Brook, are searching for other scientists to work at the Kavita and Lalit Bahl Center for Metabolomics and Imaging. “We are actively recruiting for star scientists” at the center, Obeid said. Other researchers suggested that the history of the work Obeid and Hannun have done will attract other researchers.

Hannun and Obeid are “considered the absolute leaders in the area of sphingolipid biochemistry and their clinical implications,” Raben said. “Simply put, they are at the top of this academic pile. Not only are they terrific scientists, they also have an outstanding and well-recognized reputation for training and nurturing young investigators.” Carman asked, “Who wouldn’t want to be associated with a group that continues to make seminal contributions to cancer biology and make an impact on the lives of so many?”

As for the next steps in this particular effort, Carman foresaw some ways to extend this work into the clinical arena. “I can imagine the discovery of a drug that might be used to combat cancer growth,” Carman said. “I can imagine the discovery of a drug that might control the acylation of ceramide to make ceramide more available as a cancer cell inhibitor. Clearly, [Obeid’s] group, along with the outstanding colleagues and facilities at Stony Brook, are positioned to make such discoveries.”

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Line Pouchard at the Great Smoky Mountains National Park in 2013. Photo by Allan Miller

By Daniel Dunaief

They produce so much information that they can’t keep up with it. They use the latest technology to gather data. Somewhere, hidden inside the numbers, might be the answer to current questions as well as the clues that lead to future questions researchers don’t know how to ask yet.

Scientists in almost every facility, including at Brookhaven National Laboratory, Cold Spring Harbor Laboratory and Stony Brook University, are producing information at an unprecedented rate. The Center for Data-Driven Discovery at Brookhaven National Laboratory can help interpret and make sense of all that information.

Senior researcher Line Pouchard joined BNL’s data team early this year, after a career that included 15 years at Oak Ridge National Laboratory (another Department of Energy facility) and more than two-and-a-half years at Purdue University. “The collaborations at the [DOE] lab are highly effective,” she said. “They have a common purpose and a common structure for the scientist.” Pouchard’s efforts will involve working with metadata, which adds annotations to provide context and a history of a file, and machine learning, which explores large blocks of information for patterns. “As science grows and the facility grows, we are creating more data,” she said.

Scientists can share large quantities of information, passing files through various computer systems. “You may want to know how this data has been created, what the computer applications or codes are that have been used, who developed it and who the authors are,” she said.

Knowing where the information originated can help the researchers determine whether to trust the content and the way it came together, although there are other requirements to ensure that scientists can trust the data. If the metadata and documentation are done properly “this can tell you how you can use it and what kind of applications and programs you can use to continue working with it,” Pouchard said. Working in the Computational Science Initiative, Pouchard will divide her time between responding to requests for assistance and conducting her own research.

“At Purdue, [Pouchard] was quite adept at educating others in understanding metadata, and the growing interest and emphasis on big data in particular,” explained Jean-Pierre Herubel, a professor of library science at Purdue, in an email. Herubel and Pouchard were on the research council committee, and worked together with other members to shepherd their research agendas for the Purdue University library faculty.

Pouchard “has a capacity to participate well with colleagues; regarding national and international venues, she will be a strong participating member,” Herubel continued. “She does well working and integrating with others.”

Pouchard recently joined a team that submitted a proposal in the area of earth science and data preservation. She has also worked on something called the Semantic Web. The idea, which was proposed by Tim Berners-Lee, who invented the World Wide Web, is to allow the use of data items and natural language concepts in machine readable and machine actionable forms. As an example, this could include generating rules for computers that direct the machines to handle the multiple meanings of a word.

One use of the Semantic Web is through searches, which allows people to look for information and data and, once they’re collected, gives them a chance to sort through them. Combined with other technologies, the Semantic Web can allow machines to do the equivalent of searching through enormous troves of haystacks.

“When I first started talking about the Semantic Web, I was at Oak Ridge in the early days,” Pouchard said. Since then, there has been considerable progress, and the work and effort have received more support from scientists.

Pouchard was recently asked to “work with ontologies [a Semantic Web technology] in a proposal,” she said, which suggests they are getting more traction. She is looking forward to collaborating with several scientists at BNL, including Kerstin Kleese van Dam, the director of the Computational Sciences Initiative and the interim director of the Center for Data-Driven Discovery.

Kleese van Dam has “an incredible vision of what is needed in science in order to improve computational science,” said Pouchard, who met the director about a decade ago when van Dam was working in England. Pouchard has an interest in data repositories, which she explored when she worked at Purdue University.

Living temporarily in Wading River, Pouchard bought a home in Rocky Point and hopes to move in soon. Her partner Allan Miller, from Knoxville, Tennessee, owned and managed the Disc Exchange in Knoxville for 26 years. He is starting to help small business owners and non-profit organizations with advertising needs. Pouchard experienced Long Island when she was conducting her Ph.D. research at the City University of New York and took time out to visit a friend who lived in Port Jefferson.

When she’s not working on the computer, Pouchard, who is originally from Normandy, France, enjoys scuba diving, which she has done in the Caribbean, in Hawaii, in Mexico and a host of other places.

When Pouchard was young, she visited with her grandparents during the summer at the beach in Normandy, in the town of Barneville-Carteret. Her parents, and others in the area, lectured their children never to go near or touch metal objects they found in the dunes because unexploded World War II devices were still occasionally found in remote areas. The environment on Long Island, with the marshes, reminds her of her visits years ago.

Pouchard has an M.S. in information science from the University of Tennessee and a Ph.D. in comparative literature from the City University of New York.

As for her work, Pouchard said she is “really interested in the Computational Science Initiative at BNL, which enables researchers to collaborate. Computational science is an integral part of the facilities,” at her new research home.

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Joseph Schwartz, right, with a collaborator, Daichi Shimbo, the director of the Translational Lab at the Center for Behavioral Cardiovascular Health at Columbia University Medical Center, in front of a poster they presented at an annual meeting of the American Society of Hypertension in New York City in 2013.Photo by John Booth, III

By Daniel Dunaief

The cardiovascular skies may be clear and sunny, but there could also be a storm lurking behind them. About one in eight people who get a normal reading for their blood pressure have what’s called masked hypertension.

That’s the finding in a recent study published in the American Journal of Epidemiology led by Joseph Schwartz, a professor of psychiatry and sociology at Stony Brook University and a lecturer of medicine at the Columbia University Medical Center. Schwartz said his research suggests that some people may need closer monitoring to pick up the kinds of warning signs that might lead to serious conditions.

“The literature clearly shows that those with masked hypertension are more likely to have subclinical disease and are at an increased risk of a future heart attack or stroke,” Schwartz explained in an email.

Tyla Yurgel, Schwartz’s lab manager from 2005 to 2016 who is now working in the Department of Psychiatry, wears the ambulatory blood pressure cuff that was a part of the study. Photo by Arthur Stone

Schwartz and his colleagues measured ambulatory blood pressure, in which test subjects wore a device that records blood pressure about every half hour, collecting a set of readings as a person goes about the ordinary tasks involved in his or her life. Through this reading, he was able, with some statistical monitoring, to determine that about 17 million Americans have masked hypertension, a term he coined in 2002.

Schwartz, who started studying ambulatory blood pressure in the late 1980s, has been actively exploring masked hypertension for over a decade. Ambulatory blood pressure monitoring is more effective at predicting subclinical disease such as left ventricular hypertrophy and the risk of future cardiovascular events, said Schwartz. “There was some rapidly growing evidence it was a better predictor of who would have a heart attack or stroke than in the clinic, even when the blood pressure in the clinic was properly measured,” he said.

To be sure, the expense of 24-hour monitoring of ambulatory blood pressure for everyone is unwieldy and unrealistic, Schwartz said. The list price for having an ambulatory blood pressure recording is $200 to $400, he said. Wearing the device is also a nuisance, which most people wouldn’t accept unless it was likely to be clinically useful or, as he suggested, they were paid as a research participant.

Schwartz said he used a model similar to one an economist might employ. Economists, he said, develop simulation models all the time. He said over 900 people visited the clinic three times as a part of the study. The researchers took three blood pressure readings at each visit. The average of those readings was more reliable than a single reading.

The study participants then provided 30 to 40 blood pressure readings in a day and averaged those numbers. He collected separate data for periods when people were awake or asleep. A patient close to the line for hypertension in the clinical setting was the most likely to cross the boundaries that define hypertension. “You don’t have that far to go to cross that boundary,” Schwartz said.

After analyzing the information, he came up with a rate of about 12.3 percent for masked hypertension of those with a normal clinic blood pressure. The rate was even higher, at 15.7 percent, when the researchers used an average of the nine readings taken during the patient’s first three study visits.

William White, a professor of medicine at the Calhoun Cardiology Center at the University of Connecticut School of Medicine in Farmington was a reviewer for one of these major studies. “They are excellent,” said White, who has known Schwartz for about a decade. “We should be monitoring blood pressure more outside of the clinical environment.”

Indeed, patients have become increasingly interested in checking their blood pressure outside of the doctor’s offices. “We have a 200 to 300 percent increase in requests for ambulatory blood pressure monitoring from our clinical lab during the last five to ten years — in all age groups, genders and ethnicities,” explained White.

The challenge, however, is that tracking hypertension closely for every possible patient is difficult clinically and financially. “There are no obvious clinical markers for masked hypertension other than unexpectedly high self-blood pressure or unexplained hypertensive target organ damage,” White added.

Schwartz himself has a family history that includes cardiovascular challenges. His father, Richard Schwartz, who conducted nonmedical research, has a long history of cardiovascular disease and had a heart attack at the age of 53. His grandfather had a fatal heart attack at the same age. When Schwartz reached 53, he said he had “second thoughts,” and wanted to get through that year without having a heart attack. He’s monitoring his own health carefully and is the first one in his family to take blood pressure medication.

Schwartz, who grew up in Ithaca, New York, came to Stony Brook University in 1987. He called his upbringing a “nonstressful place to grow up.” He now lives in East Setauket with his wife Madeline Taylor, who is a retired school teacher from the Middle Country school district. The couple has two children. Lia lives in Westchester and works at Graham Windham School and Jeremy lives in Chelsea and works for Credit Suisse.

As for his work, Schwartz said the current study on masked hypertension was a part of a broader effort to categorize and understand pre-clinical indications of heart problems and to track the development of hypertension.

Now that he has an estimate of how many people might have masked hypertension, he plans to explore the data further. That analysis will examine whether having masked hypertension puts a patient at risk of having cardiovascular disease or other circulatory challenges. “We are very interested in whether certain personality characteristics and/or circumstances (stressful work situation) makes it more likely that one will have masked hypertension,” he explained.

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Mount Sinai Ocean Sciences Bowl team co-advisers David Chase and Glynis Nau-Ritter with members, Ariele Mule, Ben May, Claire Dana and Jonathan Yu. Photo from Glynis Nau-Ritter

Mount Sinai High School’s Ocean Sciences Bowl team is going national.

The group recently went head-to-head at Stony Brook University against 16 other teams throughout the state, and won first place at the regional Bay Scallop Bowl, an academic competition testing the students’ knowledge of marine sciences, including biology, chemistry, physics and geology. Mount Sinai’s 28-27 win against Great Neck South High School clinched its spot in the National Ocean Sciences Bowl, where they’ll join 25 teams from across the country in Corvallis, Oregon from April 20 to 23.

“Going in, we were skeptical, but once we started going through the day, our confidence really built up and everybody got to shine.”

—Ben May

On Feb. 18, the school’s four-student “A” team — senior Ben May, junior Jonathan Yu, sophomore Claire Dana, and freshman Ariele Mule — was one of two left standing after competing in a series of 10 fast-paced, undefeated buzzer, with the next determining the winner. With three seconds left on the clock, Great Neck South ran out of time on a bonus question that would’ve made it the winner, and Mount Sinai came out victorious. The high school has now placed first in 10 of the 16 annual Bay Scallop Bowls.

“It was probably the most exciting competition we’ve had in the Ocean Bowl,” said team co-advisor Glynis Nau-Ritter, a science teacher at the high school. “We work them hard and it pays off.”

Co-advisor David Chase echoed Nau-Ritter’s excitement.

“The students here have not only won the competition, but they’ve expanded their knowledge,” he said. “I’m very proud to be able to contribute to their success, and it’s great to be working with the best of the best.”

May, the team’s captain, said he and his teammates experienced “the ultimate coming-from-behind story” after going through a reconstruction year. May was the only returning member of the “A” team from last year, as the others had all graduated.

“It was thrilling to win and have the experience with so many people who share my love of the ocean.”

—Claire Dana

“Going in, we were skeptical, but once we started going through the day, our confidence really built up and everybody got to shine,” May said. “It was the closest competition I’ve ever been part of. We had no control over it. The other team captain and I were very friendly and it was a bonding experience. The stress of it really pulled us together.”

Calling nationals “a nerd’s dream,” May expressed pride for each of his teammates and said to prepare for the nationals, they met to study over winter break and will be meeting several days a week leading up to the nationwide competition.

“It was thrilling to win and have the experience with so many people who share my love of the ocean,” Dana said. “It was a great surprise, and I thought we all found pride in each other. We were all super ecstatic.”

In addition to competing in the nationals and receiving an all-expenses paid trip to Oregon, each of the four Mount Sinai students received a check for $400 for their victory.

The highest the Mount Sinai team has placed is fourth at nationals. If the students place in the top three or four teams, there are other monetary awards, as well as a trophy and possible student accessories like a netbook. The team could also potentially win a field trip to various research stations, like the Caribbean or West Coast.

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Benjamin Martin in his lab at Stony Brook University. Photo courtesy of SBU

By Daniel Dunaief

Last week, the Times Beacon Record Newspapers profiled the work of David Matus, an assistant professor in the Department of Biochemistry and Cell Biology. Matus and Benjamin Martin, who has the same title in the same department, are working together on a new cancer study.

While neither Matus nor Martin are cancer biologists, these researchers have experience in developmental biology with different organisms that could contribute to insights in cancer. Specifically, they are exploring the processes that lead to cell division or invasion. Matus is working with the transparent roundworm, while Martin is focusing on the zebrafish.

The duo recently won the 2017 Damon Runyon–Rachleff Innovation Award, which includes a grant of $300,000. Martin got involved in the research “based on learning more about [Matus’] work and the general hypothesis” about division and invasion, Martin said. The overall perspective is that the cell doesn’t “invade through tissues and divide at the same time.”

Martin has done innovative work with a neuromesodermal progenitor in the zebrafish. These cells are highly plastic and can give rise to numerous other cell types. Martin is focused on trying to understand the basic biology of these cells.

From left, David Matus and Benjamin Martin in the lab where they investigate metastatic cancer. Photo courtesy of SBU

Martin is known for the “very original discovery that a signaling protein called Wnt can regulate the decision between these progenitor cells becoming muscle or neurons,” explained David Kimelman, a professor of Biochemistry at the University of Washington who oversaw Martin’s research when he was a postdoctoral student.

“What is very nice is that [Martin’s] discovery in zebrafish has since been replicated in other organisms such as the mouse and even in human stem cells, showing that this is a fundamental property of vertebrates,” Kimelman explained in an email.

Similar to Matus’ work with the worm, Martin has been working with cells that go through invasive behavior and don’t engage in cell proliferative activities. “We already knew that notochord progenitors are not proliferating when they undergo convergence and extension” from other published works, explained Martin in an email. “Since notochord progenitors exist in the tailbud and we were already studying them, it was a natural jumping off point to address the same question.”

Martin is testing a transcription factor, called brachyury, which drives metasasis-like behavior in human cancer cells. He has studied this transcription factor in the context of early zebrafish development and will see if it helps drive metastasis through inhibition of the cell cycle. At this point, Martin said, there is some “evidence that it does arrest the cell cycle” using human cells in another lab.

So far, the work he has done with brachyury and the cell cycle/invasion in zebrafish is preliminary. Their hypothesis is that halting the cell cycle is a prerequisite for invasive behavior. Like the roundworm, the embryonic zebrafish is transparent, which makes it easier to observe cellular changes.

One of the goals of the project is “to observe the cell cycle of human cancer as it invades through tissues in the fish embryo,” Martin said. In the long term, he hopes to see whether the overexpression of a transcription factor Matus has found in the worm is sufficient to drive metastasis in the zebrafish.

Martin described winning the Damon Runyon–Rachleff Award as “exciting,” and suggested that it “pushes back a little bit of the worry phase” of finding funding for compelling scientific projects. Kimelman said Martin is an “exceptional scientist” and one of the “best I have had the privilege to train.”

Kimelman believes the work Martin and Matus are doing has the potential to provide “important insight into the basic changes that occur during cancer as cells become metastatic,” he explained in an email. “While it doesn’t immediately lead to a therapeutic, understanding the basic biology of cancer is the first step to defining new ways of affecting it.”

Kimelman particularly appreciated the way Matus and Martin combined two different model systems, which offers the potential to provide insight into the basic changes that occur during cancer as cells become metastatic.

Martin learned about science and research during his formative years. His father Presley Martin was a graduate student at Johns Hopkins in Baltimore when the younger Martin was born. Presley Martin recently retired from Hamline University in St. Paul, Minnesota, where he studied the genetics of the fruit fly Drosophila. “At a young age, I was exposed to a lot of the lab and experiments and it was certainly appealing to me,” said Martin.

Benjamin Martin with his son Calvin. Photo by Richard Row

Martin is married to Jin Bae, whom he met at the University of California at Berkeley, where he was studying the molecular control of how muscle precursor cells move to distant parts of the embryo in frogs and fish. Bae is a registered nurse at Stony Brook Hospital. The couple’s son Calvin, who enjoys visiting the lab, will be four in April.

Matus and Martin are collaborating with Scott Powers, a professor in the Department of Pathology at Stony Brook, and Eric Brouzes, an assistant professor in the Department of Biomedical Engineering at Stony Brook.

Powers said the work Martin and Matus are doing is a “basic discovery but an important one,” he explained in an email. “Conceivably, further research could lead to translation but as of right now, any thoughts along those lines are speculative.”

Martin appreciates the opportunity to work on these cells that are so important in development and that might lead to insights about cancer. “It seems like in the past few years” these discoveries have “opened up a subfield of developmental biology,” he said. “It’s exciting to see.”

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David Matus in his lab at Stony Brook University. Photo courtesy of SBU

By Daniel Dunaief

At first look, the connection between a roundworm, a zebrafish and cancer appears distant. After all, what can a transparent worm or a tropical fish native to India and the surrounding areas reveal about a disease that ravages its victims and devastates their families each year?

Plenty, when talking to David Matus and Benjamin Martin, assistant professors in the Department of Biochemistry and Cell Biology at Stony Brook University whose labs are next door to each other. The scientific tandem recently received the 2017 Damon Runyon–Rachleff Innovation Award, which includes a two-year grant of $300,000, followed by another renewable grant of $300,000 to continue this work.

In the first of a two-part series, Times Beacon Record Newspapers will profile the work of Matus this week. Next week the Power of Three will feature Martin’s research on zebrafish.

Long ago a scientist studying dolphin cognition in Hawaii, Matus has since delved into the world of genetic development, studying the roundworm, or, as its known by its scientific name, Caenorhabditis elegans. An adult of this worm, which lives in temperate soil environments, measures about 1 millimeter, which means it would take about 70 of them lined up end to end to equal the length of an average earthworm.

From left, David Matus and Benjamin Martin. Photo courtesy of SBU

Matus specifically is interested in exploring how a cell called the anchor cell in a roundworm invades through the basement membrane, initiating a uterine-vulval connection that allows adult roundworms to pass eggs to the outside environment. He is searching for the signals and genetic changes that give the anchor cell its invasive properties.

Indeed, it was through a serendipitous discovery that he observed that the loss of a single gene results in anchor cells that divide but don’t invade. These dividing cells are still anchor cells, but they have lost the capacity to breach the basement membrane. That, Matus said, has led the team to explore the ways cancer has to decide whether to become metastatic and invade other cells or proliferate, producing more copies of itself. In some cancers, their hypothesis suggests, the cells either divide or invade and can’t do both at the same time. It could be a cancer multitasking bottleneck.

Mark Martindale, the director of the Whitney Laboratory at the University of Florida in Gainesville who was Matus’ doctoral advisor, said a cell’s decision about when to attach to other cells and when to let go involves cell polarity, the energetics of motility and a host of other factors that are impossible to study in a mammal.

The roundworm presents a system “in which it is possible to manipulate gene expression, and their clear optical properties make them ideal for imaging living cell behavior,” Martindale explained in an email. Seeing these developmental steps allows one to “understand a variety of biomedical issues.”

Last year, Matus and Martin were finalists for the Runyon–Rachleff prize. In between almost getting the award and this year, the team conducted imaging experiments in collaboration with Eric Betzig, a group leader at the Janelia Research Campus of the Howard Hughes Medical Institute in Ashburn, Virginia. Betzig not only brings expertise in optical imaging technologies but also has won a Nobel Prize.

“We really appreciate the opportunity to work with [Betzig] and his lab members on this project,” said Matus, who also published a review paper in Trends in Cell Biology that explored the link between cell cycle regulation and invasion. He and his graduate student Abraham Kohrman explored the literature to find cases that showed the same switching that he has been exploring with the roundworm.

Yusuf Hannun, the director of the Stony Brook Cancer Center, said the work is highly relevant to cancer as it explores fundamental issues about how cells behave when they invade, which is a key property of cancer cells. Hannun said the tandem’s hypothesis about division and invasion is “consistent with previous understandings but I believe this is the first time it is proposed formally,” he suggested in an email.

Their work could apply to invasive epithelial cancers, suggested Scott Powers, a professor in the Department of Pathology at Stony Brook and the director of Clinical Cancer Genomics at the Cancer Center. That could include breast, colon, prostate, lung and pancreatic cancers, noted Powers, who is a recent collaborator with Matus and Martin.

The additional funding allows Matus and Martin to focus more of their time on their research and less on applying for other grants, Matus said.

Back row from left, David Matus and his father in law Doug Killebrew; front row from left, Maile 9, Bria, 7, and Matus’ wife Deirdre Killebrew. Photo by Richard Row

Matus lives in East Setauket with his wife Deirdre Killebrew, who works for Applied DNA Sciences. The couple met when they were working with dolphins in Hawaii. Matus’ first paper was on dolphin cognition, although he switched to evolutionary and developmental biology when he worked in Martindale’s lab at the University of Hawaii.

Martindale described Matus as prolific during his time in his lab, publishing numerous papers that were “profoundly important in our continued understanding of the relationship between genotype and phenotype and the evolution of biological complexity,” Martindale wrote in an email.

Following in Martindale’s footsteps, Matus replaced his middle name, Samuel, in publications with a Q. Martindale said several of his colleagues adopted the phony Q to pay homage to the attitude that drove them to pursue careers in science. Matus has now passed that Q on to Korhman, who is his first graduate student.

Matus and Killibrew have two daughters, Bria and Maille, who are 7 and 9 years old. Their children have a last name that combines each of their surnames, Matubrew. Matus said he feels “fortunate when I got here three years ago that they had me set up my lab next to [Martin]. That gave us an instantaneous atmosphere for collaboration.”

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By Daniel Dunaief

 

Adrian Krainer with Emma Larson earlier this year. Photo from Dianne Larson

The prognosis hit Dianne Larson of Middle Island hard. Within three weeks, anxiety attacks, a lack of sleep and fear caused her weight to plummet from 135 to 120 pounds. She found out her daughter Emma, who was 17 months old at the time, had a potentially fatal genetic condition called spinal muscular atrophy in which the motor nerve cells of the spinal cord progressively weaken. Normally, the SMN1 gene produces the survival of motor neuron protein, which, as its name suggests, helps maintain motor neurons. People with SMA, which has four types and severity, produce a lower amount of the functional protein.

“My mind went to the darkest of dark places,” said Larson, whose daughter couldn’t crawl or sit up to eat. “There was no hope. There was nothing I could do.”

At the time of Emma’s diagnosis, there was no treatment for a disease that is the leading genetic cause of death among infants and affects about 1 in 10,000 newborns. Thanks to the work of Adrian Krainer, a professor and program chair of cancer and molecular biology at Cold Spring Harbor Laboratory, that changed early enough to alter the expectations for Emma and children around the world battling a genetic condition that causes progressive weakness and can make moving and even breathing difficult.

Turning to a back up gene called SMN2, Krainer hoped to fix a problem with the way that gene is spliced. On SMN2, exon 7 is normally skipped and the resulting protein has a different sequence at the end. Krainer developed an antisense olignocleotide that binds to a sequence in the intro following exon 7, blocking the splicing receptor. The treatment, which is called Spinraza, helps guide the splicing machinery, which carries out one of the steps in gene expression that is necessary to build a functional protein.

The Larson family of Middle Island, from left, Dianne, Emma and Matthew. Photo from Dianne Larson

Larson had heard of Krainer’s work and was eager to see if his success with animal models of the disease would translate for humans. As soon as Emma reached her second birthday, Larson enrolled her daughter in a clinical trial for Spinraza. After her daughter had a few shots, Larson was stunned by the change. “I was in the master bedroom and she was in the den and I heard a voice getting closer,” Larson recalls. “Next thing I know, she was in my bedroom. I couldn’t believe she crawled from the den to the bedroom. I put her in the den and told her to do it again,” which she did.

The SMA community and Krainer received an early holiday present in late December when the Food and Drug Administration not only approved the treatment, but it also gave doctors the green light to prescribe it for all types of SMA and for patients of all ages. While the SMA community, doctors and Krainer have been delighted with the FDA approval, the excitement has been tempered by concerns about the price tag Biogen, which manufactures and commercializes Spinraza and funded the drug’s development, has placed on the treatment.

For the first full year of injections, the drug costs $750,000. Every year after that will cost $375,000, which Biogen has said publicly is consistent with the pricing for other drugs for so-called orphan diseases, which affect a much smaller percentage of the population.

Knowledge Ecology International, a nonprofit advocate for affordable medicines, sent a letter to the Office of the Inspector General at the Department of Health and Human Services, seeking an investigation. The letter claims that the inventor and maker of Spinraza failed to disclose that the treatment received federal funding. KEI urges the government to use that alleged disclosure failure to end the patent and authorize a generic manufacture of the treatment.

Biogen didn’t return a call and email for comment. Patients and their families, meanwhile, are looking for immediate access to a life-altering treatment. “To be honest, I really don’t know what we’re going to do,” said Larson, whose daughter has four injections left as part of the extension trial soon. “I’m hoping insurance will cover it.”

Insurer Anthem announced late in January that the treatment was only medically necessary for patients with Type 1 SMA, which include people diagnosed with the disease within six months of birth. Anthem created a pay for performance model, which will require patients or their families to prove that the treatment is improving the lives of the recipients.

Larson said she has been in touch with a personal liaison at Biogen, which has been “helpful and supportive,” she said. “They have been going out of their way to reach out to the community to make sure everyone gets access.”

Larson, who is a financial advisor, said she understands the need for the company to generate a profit. “A lot of money goes into” research and development Larson said. “If they’re not gong to make money, they’re not going to” support the efforts to create a treatment.

Emma Larson will be turning 4 this month. Photo from Dianne Larson

Joe Slay, who is the chairman of FightSMA, a group he and his wife Martha founded in 1991 after they learned their son Andrew had Type 2 SMA, sounded hopeful that people who need this treatment will receive it. “I understand there’s constructive, good conversations between insurance companies and Biogen,” Slay said. “We’re monitoring that.”

While Andrew, who is now 30, considers the potential benefits of Spinraza, Slay is pleased the treatment is an option for people and is proud of Krainer’s work.Krainer is “by any definition of the word a hero,” Slay said. “He’s taken his natural gifts, his brilliance in science, his discipline year in and year out approach to his work and has applied himself 100 percent.”

Slay and FightSMA, which has raised over $8 million since its founding, helped provide seed money to Krainer more than 15 years ago, attracting a promising scientist to what was then an intractable medical challenge.

Tom Maniatis, who is the chairman of the Department of Biochemistry and Molecular Biophysics at Columbia University, said Krainer, who did his doctoral work in Maniatis’s lab, showed considerable scientific promise early in his career. Krainer “clearly had the intelligence, drive and experimental skills to make important contributions,” Maniatis said. His work is “a perfect example of how deep basic science studies can lead to profound understanding of a disease mechanism and that, in turn to the development of a treatment,” explained Maniatis in an email.

Within Krainer’s own family, there is a connection to patient care. Krainer’s daughter Emily, who is a pediatric neurology resident at Rochester, may one day prescribe a treatment her father developed. “It will be quite something for me if she eventually prescribes Spinraza to one of her patients,” Krainer said. Even as other scientists and companies like AveXis continue to search for ways to treat SMA, Krainer enhances and refines his research.

“We continue to work on understanding aspects of SMA pathophysiology, the role of SMN levels outside the central nervous system and the potential for prenatal therapy,” he explained in an email. “We are also working on antisense therapies for other genetic diseases and cancer.”

Larson, who is overjoyed with her daughter’s progress, calls Krainer her “superhero” who “saved my daughter’s life.” “It’s such a different feeling when you know you can do something,” she said. When she found out that the FDA approved the treatment, it was “the best day.”

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By Elof Axel Carlson

Elof Axel Carlson

There are millions of species of living things. Until the 1860s biologists divided them into two kingdoms, animals and plants.

Louis Pasteur revealed a third group of microscopic bacteria that caused disease, fermented foods (like cheeses), rotted food and decomposed dead organisms. In the mid-20th century this third group, known as prokaryotes, was shown to consist of eubacteria and archaea, differing mostly in how they used energy to carry out their living activities.

Bacteria mostly use oxygen, sunlight and carbon dioxide as fuels and an energy source. Some bacteria are like green plants and use chlorophyll to convert carbon molecules to food and release oxygen. Most of Earth’s atmosphere arose from that early growth of photosynthetic bacteria. Archaea mostly use sulfur, superheated water and more extreme environmental conditions (like deep sea vents) for their energy.

Biologists today identify cellular life as having three domains — archaea, bacteria and eukaryotes. We belong to the eukaryotes whose cells have nuclei with chromosomes. The eukaryotes include multicellular animals, multicellular plants, unicellular protozoa (protists), unicellular algae and fungi.

The two prokaryotic domains and the five eukaryotic groups are designated as kingdoms. A rough time table of early life on Earth would put prokaryotic life about 3.5 to 3.8 billion years ago, the first free oxygen in our atmosphere about 3.5 billion years ago, the first eukaryotic cells about 2.5 billion years ago and the first multicellular organisms about 1.5 billion years ago.

The branches of the tree of life biologists construct have an earliest ancestor called LUCA (for the last universal common ancestor of a particular branch). There may have been a biochemical evolution preceding the formation of the first cellular LUCA with RNA and protein associations, RNA and DNA associations and virus-like sequences of nucleic acids.

The three domains have produced six million different genes. Molecular biologists have identified 355 genes that all cellular organisms share in common. This is possibly the genome of the LUCA of all living cellular organisms. Whether such a synthetic DNA chromosome could be inserted into a bacterial or archaeal cell or even a eukaryotic cell whose own DNA has been removed has not yet been attempted. It may not work because we know little about the non-DNA components of bacterial or archaeal cells.

Biologists have known for some time that a nucleus of a distant species (e.g., a frog) placed in a mouse egg whose nucleus has been removed will not divide or produce a living organism. But two closely related species (like algae of the genus Acetabularia) can develop after swapping nuclei. In such cases the growing organism with the donated nucleus resembles the features of the nuclear donor.

There is a LUCA for the first primate branch with the genus Homo. We are described as Homo sapiens. Anthropologists and paleontologists studying fossil human remains have worked out the twigs of the branch we identify as the genus Homo. Neanderthals and Denisovans (about 500,000 years ago) are the two most recent branches that preceded the origins of H. sapiens (about 160,000 years ago). Most humans have a small percentage of Neanderthal or Denisovan genes. Fossils of Homo erectus (about 1.8 million years ago) or Homo habilis (about 2.8 million years ago) are much older than the recent three species of Homo. Those fossils do not have DNA that can be extracted from teeth.

A second objective of studying LUCA’s 355 genes will be the identification of each gene’s function. That will tell biologists what it is that makes these genes essential in all cellular organisms.

I can think of a third important consequence of studying LUCA. There are millions of different viruses on Earth, especially in the oceans. If cellularity arose from clusters of viruses, the genes of the mother of all LUCAs may be scattered among some of those viruses and give biologists insights into the step-by-step formation of that first LUCA cell.

In Gilbert and Sullivan’s operetta, “The Mikado,” one character boasts of tracing his ancestors to a primordial bit of protoplasm. The genome of LUCA might become an unexpected example where science imitates art.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

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By Daniel Dunaief

First responders, soldiers or those exposed to any kind of chemical weapons attack need a way to remove the gas from the air. While masks with activated carbon have been effective, the latest technological breakthrough involving a metal organic framework may not only remove the gas, but it could also disarm and decompose it.

That’s the recent finding from research led by Anatoly Frenkel in a study on a substance that simulates the action of sarin nerve gas.

Frenkel, who is a senior chemist at Brookhaven National Laboratory and a professor in the Department of Materials Science and Chemical Engineering at Stony Brook University, worked with metal organic frameworks, which contain zirconium cluster nodes that are connected through a lattice of organic linkages.

Anatoly Frenkel with his son, Yoni, at Lake Hopatcong in New Jersey. Photo by Mikhail Loutsenko.

These structures would “do the job even without any catalytic activity,” Frenkel said, because they are porous and capture gases as they pass through them. “It’s like a sponge that can take in moisture. Its high porosity was already an asset.”

Frenkel and his colleagues, which include John Morris and Diego Troya from Virginia Tech, Wesley Gordon from Edgewood Chemical Biological Center and Craig Hill from Emory University, among other contributors, suspected that these frameworks might also decompose the gas.

Theoretically, researchers had predicted this might be the case, although they had no proof. Frenkel and his team used a differential method to see what was left in the structure after the gas passed through. Their studies demonstrated a high density of electrons near the zirconium atoms. “These were like bread crumbs congregated around a place where the zirconium nodes with the connecting linkers were,” Frenkel said.

While this work, which the scientists published in the Journal of the American Chemical Society, has implications for protecting soldiers or civilians in the event of a chemical weapons attack, Frenkel and his colleagues, who received funding from the Defense Threat Reduction Agency, can share their results with the public and scientific community because they are not working on classified materials and they used a substance that’s similar to a nerve gas and not sarin or any other potentially lethal gas.

“This knowledge can be transferred to classified research,” Frenkel said. “This is a stepping stone.” Indeed, Frenkel can envision the creation of a mask that includes a metal organic framework that removes deadly nerve gases from the air and, at the same time, disarms the gas, providing a defense for first responders or the military after a chemical weapons attack. Even though he doesn’t work in this arena, Frenkel also described how manufacturers might use these frameworks in treating the fabric that is used to make clothing that can prevent gases that can be harmful to the skin from making contact.

A physicist by training, Frenkel’s work, which includes collaborations on five other grants, has a common theme: He explores the relationship between structure and function, particularly in the world of nanomaterials, where smaller materials with large surface areas have applications in a range of industries, from storing and transmitting energy to delivering drugs or pharmaceuticals to a targeted site.

Eric Stach, a group leader in electron microscopy at BNL, has collaborated with Frenkel and suggested that his colleague has helped “develop all these approaches for characterizing these materials.” Stach said that Frenkel has “an outstanding reputation internationally” as an expert in X-ray absorption spectroscopy, and, in particular, a subarea that allows scientists to learn about extremely subtle changes in the distance between atoms when they are subjected to reactive environments.

Frenkel said some of the next steps in the work with metal organic frameworks include understanding how these materials might become saturated with decomposed gas after they perform their catalytic function. “It’s not clear what can affect saturation,” he said, and that is something that “needs to be systematically investigated.” After the catalyst reaches saturation, it would also be helpful to know whether it’s possible to remove the remaining compound and reuse the catalyst.

“The next question is whether to discard” the framework after it’s trapped and deactivated the chemicals or regenerate it, Frenkel said. He is also exploring how temperature ranges might affect the performance of the framework. Ideally, it would function as well in an arctic environment as it would in a desert under extreme heat. A commercial application might require the synthesis of a material with different physical characteristics for a range of temperature conditions.

Frenkel has been working on this project for about one and a half years. A colleague approached him to become a part of this new collaboration. “My role was to bring this work to a national lab setting,” where the scientists could use the advanced tools at BNL to study the material as it was working, he said.

A resident of Great Neck, Frenkel, who grew up in St. Petersburg, Russia, lives with his wife Hope Chafiian, a teacher at the Spence School in Manhattan for almost 30 years. He has three children: Yoni lives in Manhattan and works at JP Morgan Chase, Ariela is a student at Binghampton and Sophie is in middle school in Great Neck.

Frenkel appreciates the opportunity to explore the broader world of nanomaterials, which, he said, are not constrained by crystal structures and can be synthesized by design. “They show a lot of mysteries that are not understood fully,” he said. Indeed, Frenkel explained that there are numerous commercial processes that might benefit from design studies conducted by scientists. As for his work with metal organic frameworks, he said “there’s no way to overestimate how important [it is] to do work that has a practical application that improves technology, saves costs, protects the environment” and/or has the potential to save lives.

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From left, outgoing Secretary of the Department of Energy Ernest Moniz with BNL Laboratory Director Doon Gibbs taken at the opening of the National Synchrotron Light Source II at BNL. Photo courtesy of BNL

By Daniel Dunaief

Before Ernest Moniz ends his tenure as Secretary of the Department of Energy, he and his department released the first annual report on the state of the 17 national laboratories, which include Brookhaven National Laboratory.

On a recent conference call with reporters, Moniz described the labs as a “vital set of scientific organizations” that are “critical” for the department and the country’s missions. Experts from the labs have served as a resource for oil spills, gas leaks and nuclear reactor problems, including the meltdown at Fukushima in 2011 that was triggered by a deadly tsunami. “They are a resource on call,” Moniz said.

In addition to providing an overview of the benefit and contribution of the labs as a whole, the annual report also offered a look at each of the labs, while highlighting a research finding and a translational technology that has or will reach the market. In its outline of BNL, the report heralded an “exciting new chapter of discovery” triggered by the completion of the National Synchrotron Light Source II, a facility that allows researchers at BNL and those around the world who visit the user facility to explore a material’s properties and functions with an incredibly fine resolution and sensitivity.

Indeed, scientists are already exploring minute inner workings of a battery as it is operating, while they are also exploring the structure of materials that could become a part of new technology. The DOE chose to shine a spotlight on the work Ralf Seidl, a physicist from the RIKEN-BNL Research Center, has done with several collaborators to study a question best suited for answers at the Relativistic Heavy Ion Collider.

Seidl and his colleagues are exploring what gives protons their spin, which can affect its optical, electrical and magnetic characteristics. The source of that spin, which researchers describe not in terms of a top spinning on a table but rather as an intrinsic and measurable form of angular momentum, was a mystery.

Up until the 1980s, researchers believed three subatomic particles inside the proton created its spin. These quarks, however, only account for a third of the spin. Using RHIC, however, scientists were able to collide protons that were all spinning in a certain direction when they smash into each other. They compared the results to protons colliding when their spins are in opposite directions.

More recently, Seidl and his colleagues, using higher energy collisions, have been able to see the role the gluons, which are smaller and hold quarks together, play in a proton’s spin. The gluons hadn’t received much attention until the last 20 years, after experiments at CERN, in Geneva, demonstrated a lower contribution from quarks. “We have some strong evidence that gluons play a role,” Seidl said from Japan, where he’s working as a part of an international collaboration dedicated to understanding spin.

Smaller and more abundant than quarks, gluons are like termites in the Serengeti desert in Africa: They are hard to see but, collectively, play an important role. In the same report, the DOE also celebrated BNL’s work with fuel cell catalysts. A senior chemist at BNL, Radoslav Adzic developed a cheaper, more effective nanocatalyst for fuel cell vehicles. Catalysts for fuel cells use platinum, which is expensive and fragile. Over the last decade, Adzic and his collaborators have developed a one-atom-thick platinum coating over cheaper metals like palladium. Working with BNL staff scientists Jia Wang, Miomir Vukmirovic and Kotaro Sasaki, he developed the synthesis for this catalyst and worked to understand its potential use.

N.E. Chemcat Corporation has licensed the design and manufacturing process of a catalyst that can be used to make fuel cells as a part of a zero-emission car. This catalyst has the ultra low platinum content of about two to five grams per car, Adzic said. Working at BNL enabled partnerships that facilitated these efforts, he said. “There is expertise in various areas and aspects of the behavior of catalysts that is available at the same place,” Adzic observed. “The efficiency of research is much more convenient.”

Adzic, who has been at BNL for 24 years, said he has been able to make basic and applied research discoveries through his work at the national lab. He has 16 patents for these various catalysts, and he hopes some of them will get licensed. Adzic hopes this report, and the spotlight on his and other research efforts, will inspire politicians and decision makers to understand the possibility of direct energy conversion. “There are great advances in fuel cell development,” Adzic said. “It’s at the point in time where we have to do some finishing work to get a huge benefit for the environment.”

At the same time, the efficiency of fuel-cell-powered vehicles increases their economic benefit for consumers. The efficiency of an internal combustion engine is about 15 percent, whereas a fuel cell has about 60 percent efficiency, Adzic said.

BNL’s Laboratory Director Doon Gibbs welcomed the DOE publication. “This report highlights the remarkable achievements over the past decade of our national lab system — one that is unparalleled in the world,” he said. Gibbs suggested that the advanced details in the report, including the recognition for the NSLS II, span the breadth of BNL’s work. “They’re just a snapshot of what we do every day to make the world a better place,” Gibbs said.

While the annual report is one of Moniz’s final acts as the secretary of the agency, he hopes to communicate the vitality and importance of these labs and their work to the next administration.“I will be talking more with secretary nominee [Richard] Perry about the labs again as a critical jewel and resource,” Moniz said. “There’s a lot of support in Congress.” Moniz said the DOE has had five or six lab days, where labs share various displays with members of the legislative body. Those showcases have been “well-received” and he “fully expects the labs to be vital to the department.”

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