Power of 3

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.

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.”

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.”

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.”

Liliana Davalos, right in blue and white shirt, in La Victoria, Colombia with the paleo team from Grand Valley State University during a fossil dig last year. Photo courtesy of Siobhán Cooke

By Daniel Dunaief 

It’s like that old bus riddle. The bus starts out with 20 people. Six people get off, then eight get on, two more get off, 12 enter, eight exit, and so on until, lo and behold, the bus has either the same number of people or someone asks the identity of the driver.

In this case, though, the bus is a collection of Caribbean islands called the Greater Antilles, which includes the Dominican Republic, Cuba, Hispaniola, Haiti, Puerto Rico, the Cayman Islands and Jamaica. The passengers are not people; they are species of bats.

Working with Luis Valente, a postdoctoral researcher at the Natural History Museum of Berlin, Liliana Davalos, an associate professor of conservation biology/ecology and evolution at Stony Brook University, recently determined that the number of species of bats, like the people entering and leaving the bus, remained in relative equilibrium for millions of years over many generations.

Liliana Davalos at La Venta site in Colombia with a rainbow in the background.Photo courtesy of Siobhán Cooke

While several species of bats will colonize the islands and new species will also form over that long time scale, the rate of natural extinction in that time balances out the islands’ diversity gains, leaving the metaphorical bus with about the same number of species.

Famous biologists Edward O. Wilson and Robert MacArthur came up with the theory of island biogeography in 1967, which might help explain how the number of species of bats remained in equilibrium for millions of years. The theory proposes an equilibrium between colonization and extinction.

For bats, however, that balance changed. About 20,000 years ago, fossils of extinct species made their final appearance, while other species died off about 3,000 to 4,000 years ago. So, what happened to the bat bus?

The last ice age accounts for some of the declines about 20,000 years ago. More recently, the arrival of people altered conditions on the islands. At least two other waves of colonization occurred before the arrival of Europeans, with people changing the landscape through agriculture. While hunting of other mammals is evident from the archeological record, it is less certain how changes on the land affected bats. It’s difficult to pinpoint the exact time when each species went extinct, although many of those events happened after people arrived on the islands, changing the region’s equilibrium.

Davalos’ previous work had found that the number of species lost was as predicted if the losses occurred because of the rising sea levels at the end of the last glaciation. If that were the case, many of those species would have disappeared around that time. Some of her colleagues, however, dated the remains of bats and found that these species became extinct more recently, over the last few thousand years.

“While we cannot be certain that all bat extinctions were caused by humans, evidence increasingly seems to suggest so,” explained Valente in an email. “All over the world, colonization of islands by humans has led to many extinctions of local species, because islands have very unique species that are very prone to any disturbances.”

The researchers used computer simulations to calculate that it would take nature eight million years to restore bat biodiversity. “Some people argue that if we leave nature alone it will quickly return to its original state,” Valente explained. “However, the finding that it would take eight million years to recover lost diversity suggests that is clearly not the case.” Valente, who described Davalos as a “wonderful collaborator” who was “actively involved in the project at all stages,” wrote that this study “raises awareness for conservation of the unique bat species of the Caribbean.”

While there is still work ahead, the “nations of the Greater Antilles have amazing natural parks to protect their biodiversity,” Davalos explained. In the tropics of the Western Hemisphere, Puerto Rico is the “number one example of a forest growing back,” Davalos said. “Puerto Rico is one of the places in the world that has had more of a resurgence of the forest.”

The preservation of biodiversity remains threatened even now as at least three bat populations on the Greater Antilles are threatened with extinction and two might already be extinct. Still, the effort is not “hopeless,” she said, as there are some large populations of bats thriving on these islands. Davalos and her colleagues were able to make these discoveries by examining the bat in detail.

A resident of Setauket, Davalos has been at Stony Brook University for eight years. She enjoys kayaking on Long Island and visiting local and state parks. Over the last few years, she has spent her free time on staycations, where she sees a protected area of Long Island each day.

From a young age, Davalos recalls being interested in science. Indeed, when she was only 4, she saw a documentary where Louis and Mary Leakey showed the results of their expeditions where they collected human fossils in Kenya. “From that moment on,” Davalos recalled, “I thought, ‘Some day, this is what I’m going to study.’” Her family and their acquaintances suggested that pursuing such a career path would be challenging.

She tells her current SBU students that she’s “the luckiest person in the world, living out my childhood dream.” Last year, she went on her first fossil dig in Colombia, where she joined a team from Grand Valley State University in Allendale, Michigan, and Johns Hopkins. She found fossils from bats that were 12 million years old.

While Davalos has never met the Leakey family, she wants to tell them that, “Children are watching and [their work] can have a huge effect” on their dreams. Some day, Davalos hopes a future scientist may say the same thing about her research.

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.

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.”

By Daniel Dunaief

Born in Berlin just before World War II, Eckard Wimmer has dedicated himself in the last 20 years to producing something that would benefit humankind. A distinguished professor in molecular genetics and microbiology at Stony Brook University, Wimmer is hoping to produce vaccines to prevent the spread of viruses ranging from influenza, to Zika, to dengue fever, each of which can have significant health consequences for people around the world.

Using the latest technology, Wimmer, Steffen Mueller and J. Robert Coleman started a company called Codagenix in Melville. They aim to use software to alter the genes of viruses to make vaccines. “The technology we developed is unique,” said Wimmer, who serves as senior scientific advisor and co-founder of the new company.

Mueller is the president and chief science officer and Coleman is the chief operating officer. Both worked for years in Wimmer’s lab. Despite the potential to create vaccines that could treat people around the world facing the prospect of debilitating illnesses, Wimmer and his collaborators weren’t able to attract a pharmaceutical company willing to invest in a new technology that, he estimates, will take millions of dollars to figure out its value.“Nobody with a lot of money may want to take the risk, so we overcame that barrier right now,” he said.

Eckard Wimmer in his lab. Photo by Naif Mohammed Almojarthi

Codagenix has $6.2 million in funding. The National Institutes of Health initially contributed $600,000. The company scored an additional $1.4 million from NIH. It also raised $4.2 million from venture capital, which includes $4 million from TopSpin and $100,000 from Accelerate Long Island and a similar amount from the Center for Biotechnology at Stony Brook University.

Stony Brook University recently entered an exclusive licensing agreement with Codagenix to commercialize this viral vaccine platform. Codagenix is scheduled to begin phase I trials on a vaccine for seasonal influenza this year.

The key to this technology came from a SBU collaboration that included Wimmer, Bruce Futcher in the Department of Molecular Genetics & Microbiology and Steven Skiena in the Department of Computer Science. The team figured out a way to use gene manipulation and computer algorithms to alter the genes in a virus. The change weakens the virus, giving the attack dog elements of the immune system a strong scent to seek out and destroy any real viruses in the event of exposure.

Wimmer explained that the process starts with a thorough analysis of a virus’s genes. Once scientists determine the genetic code, they can introduce hundreds or even thousands of changes in the nucleic acids that make up the sequence. A computer helps select the areas to alter, which is a rapid process and, in a computer model, can take only one afternoon. From there, the researchers conduct experiments in tissue culture cells and then move on to experiment on animals, typically mice. This can take six months, which is a short time compared to the classical way, Wimmer said.

At this point, Codagenix has a collaboration with the Universidad de Puerto Rico at the Caribbean Primate Research Center to treat dengue and Zika virus in primates. To be sure, some promising vaccines in the past have been taken off the market because of unexpected side effects or even because they have become ineffective after the virus in the vaccine undergoes mutations that return it to its pathogenic state. Wimmer believes this is unlikely because he is introducing 1,000 changes within a vaccine candidate, which is much higher than other vaccines. In 2000, for example, it was discovered that the polio vaccines involve only five to 50 mutations and that these viruses had a propensity to revert, which was rare, to the type that could cause polio.

Colleagues suggested that this technique was promising. “This approach, given that numerous mutations are involved, has the advantage of both attenuation and genetic stability of the attenuated phenotype,” Charles Rice, the Maurice R. and Corrine P. Greenberg professor in virology at Rockefeller University explained in an email.

While Wimmer is changing the genome, he is not altering the structure of the proteins the attenuated virus produces, which is exactly the same as the virus. This gives the immune system a target it can recognize and destroy that is specific to the virus. Wimmer and his associates are monitoring the effect of the vaccines on mosquitoes that carry and transmit them to humans. “It’s not that we worry about the mosquito getting sick,” he said. “We have to worry whether the mosquito can propagate this virus better than before.” Preliminary results show that this is not the case, he said.

Wimmer said there are many safety precautions the company is taking, including ensuring that the vaccine candidate is safe to administer to humans. Wimmer moved from Berlin to Saxony after his father died when Wimmer was 3. He earned an undergraduate degree in chemistry in 1956 at the University of Rockstock. When he was working on his second postdoctoral fellowship at the University of British Columbia in Vancouver, he heard a talk on viruses, which brought him into the field.

A resident of Old Field, Wimmer lives with his wife Astrid, a retired English professor at Stony Brook. The couple’s daughter Susanne lives in New Hampshire and has three children, while their son Thomas lives in Portland, Oregon, and has one child. “We’re very happy Long Islanders,” said Wimmer, who likes to be near the ocean and Manhattan.

Through a career spanning over 50 years, Wimmer has won numerous awards and distinctions. He demonstrated the chemical structure of the polio genome and worked on polio pathogenesis and human receptor for polio. He also published the first cell-free creation of a virus.

“This was an amazing result that enabled a number of important mechanistic studies on poliovirus replication,” Rice explained. Wimmer has “always been fearless and innovative, with great enthusiasm for virology and discovery.”

With this new effort, Wimmer feels he will continue in his quest to contributing to humanity.

Esther Takeuchi with photo in the background of her with President Obama, when she won the 2009 National Medal of Technology and Innovation. Photo courtesy of Brookhaven National Laboratory

By Daniel Dunaief

Pop them in the back of a cell phone and they work, most of the time. Sometimes, they only do their job a short time, discharge or generate so much heat that they become a hazard, much to the disappointment of the manufacturers and the consumers who bought electronic device.

Esther Takeuchi, a SUNY distinguished professor in the Departments of Chemistry and Materials Science and Engineering and the chief scientist in the Energy Sciences Directorate at Brookhaven National Laboratory leads a team of scientists who are exploring what makes one battery work while another falters or fails. She is investigating how to improve the efficiency of batteries so they can deliver more energy as electricity.

Esther Takeuchi with a device that allows her to test batteries under various conditions to see how they function. Photo courtesy of Brookhaven National Laboratory

The process of manufacturing batteries and storing energy is driven largely by commercial efforts in which companies put the ingredients together in ways that have, up until now, worked to produce energy. Scientists like Takeuchi, however, want to know what’s under the battery casing, as ions and electrons move beneath the surface to create a charge.

Recently, Takeuchi and a team that includes her husband Kenneth Takeuchi and Amy Marschilok, along with 18 postdoctoral and graduate students, made some progress in tackling energy storage activity in iron oxides.

These compounds have a mixed track record among energy scientists. That, Takeuchi said, is what attracted her and the team to them. Studying the literature on iron oxides, her graduate students discovered “everything from, ‘it looks terrible’ to, ‘it looks incredibly good,’” she said. “It is a challenging system to study, but is important to understand.”

This offered promise, not only in finding out what might make one set of iron oxides more effective in holding a charge without generating heat — the energy-robbing by-product of these reactions — but also in providing a greater awareness of the variables that can affect a battery’s performance.

In addition to determining how iron oxides function, Takeuchi would like to “determine whether these [iron oxides] can be useful and workable.” Scientists working with iron oxides didn’t know what factors to control in manufacturing their prospective batteries.

Takeuchi said her group is focusing on the linkage between small-scale and mesoscale particles and how that influences battery performance. “The benefit of iron oxides is that they are fairly inexpensive, are available, and are nontoxic,” she said, and they offer the potential of high energy content. They are related to rust in a broad sense. They could, theoretically, contain 2.5 times more energy than today’s batteries. “By understanding the fundamental mechanisms, we can move forward to understand their limitations,” she said, which, ultimately, could result in making these a viable energy storage material. T

akeuchi is also looking at a manganese oxide material in which the metal center and the oxygen connect, creating a tube-like structure, which allows ions to move along a track. When she started working with this material, she imagined that any ion that got stuck would cause reactions to stop, much as a stalled car in the Lincoln Tunnel leads to long traffic delays because the cars behind the blockage have nowhere to go.

Takeuchi said the ions don’t have the same problems as cars in a tunnel. She and her team believe the tunnel walls are porous, which would explain why something that looks like it should only produce a result that’s 5 percent different instead involves a process that’s 80 percent different. “These escape points are an interesting discovery, which means the materials have characteristics that weren’t anticipated,” Takeuchi said. The next step, she said, is to see if the researchers can control the technique to tune the material and make it into the constructs that take advantage of this more efficient flow of ions.

Through a career that included stops in Buffalo and North Carolina and West Virginia, Takeuchi, who has over 150 patents to her name, has collected numerous awards and received considerable recognition. She won the 2009 National Medal of Technology and Innovation, a presidential award given at a ceremony in the West Wing of the White House. Takeuchi developed compact lithium batteries for implantable cardiac defibrillators.

Takeuchi is currently a member of the National Medal of Technology and Innovation Nomination Evaluation Committee, which makes recommendations for the medal to the president. Scientists who have known Takeuchi for years applaud the work she and her team are doing on Long Island. “Dr. Takeuchi and her research group are making great advances in battery research that are very clearly promoted by the strong relationship between Stony Brook and BNL,” said Steven Suib, the director of the Institute for Materials Science at the University of Connecticut.

Indeed, at BNL, Takeuchi has used the National Synchrotron Light Source II, which became operational last year. The light source uses extremely powerful X-rays to create incredibly detailed images. She has worked with three beamlines on her research. At the same time, Takeuchi collaborates with researchers at the Center for Functional Nanomaterials at BNL.

Although she works with real-world experiments, Takeuchi partners with scientists at Stony Brook, BNL and Columbia University who focus on theoretical possibilities, offering her an insight into what might be happening or be possible. There are times when she and her team have observed some interaction with batteries, and she’s asked the theorists to help rationalize her finding. Other times, theorists have suggested what experimentalists should search for in the lab.

A resident of South Setauket, Takeuchi and her husband enjoy Long Island beaches. Even during the colder weather, they bundle up and enjoy the coastline. “There’s nothing more mentally soothing and energizing” than going for a long walk on the beach, she said.

In her research, Takeuchi and her team are focused on understanding the limitations of battery materials. Other battery experts believe her efforts are paying dividends. Suib said the recent work could be “very important in the development of new, inexpensive battery materials.”

Huloin Xin. Photo courtesy of Brookhaven National Laboratory

By Daniel Dunaief

The unexpected appearance of Swiss cheese may be preferable to the predicted presence of a balloon. When it comes to the creation of catalysts for fuel-cell-powered vehicles, the formation of a structure that has miniature holes in it may reduce costs and improve energy efficiency.

Using a state-of-the-art facility where he also supports the work of other scientists around the world, Huolin Xin, an associate materials scientist at the Center for Functional Nanomaterials at Brookhaven National Laboratory, recently made the discovery about the structure of a cheaper catalyst. Xin and his collaborators published their work in Nature Communications.

Huloin Xin. Photo courtesy of Brookhaven National Laboratory

The finding “goes against conventional wisdom,” Xin said. “If you have a precursor that’s nanometers in size that’s a metal and you heat it up in oxygen, normally, it would grow into a hollow structure, like a balloon.” Instead, Xin and his colleagues discovered that mixing nickel and cobalt produces a structure that has porosity but is more like spherical Swiss cheese than a balloon. The new architecture has more material crammed into a smaller region than the hollow balloon. It is also stronger, creating a broader range of potential applications.

Scientists at Brookhaven and at other institutions around the world are seeking ways to take advantage of the growing field of nanotechnology, in which physical, electrical or other types of interactions differ from the macromolecular world of hammers, nails and airplane wings. These nanomaterials take advantage of the high surface area to volume ratio, which offers promise for future technologies. What that means is that these materials contain numerous surfaces without taking up much space, like an intricate piece of origami, or, in Xin’s case, a sphere with higher packing density.

The potential new catalyst could be used as a part of an oxygen reduction reaction in an alkaline environment. In a car that uses hydrogen, the reaction would produce water with zero emissions, Xin said. To see the structure of this catalyst, Xin used environmental transmission electron microscopy and electron tomography. The TEM uses computed axial tomography. This is similar to the CAT scan in a hospital, except that the sample Xin studied was much smaller, about 100 nanometers in size, which is 100 times thinner than the width of a human hair.

In addition to determining and defining the structure of the final product, scientists are trying to understand the process that led to that configuration. They can use the environmental transmission electron microscope, which allows gas flowing to study the formation of the catalyst.

Charles Black, the director at the Center for Functional Nanomaterials, said Xin is “off the charts talented” and is a “world leader” in figuring out ways to get more information from the electron microscope. Xin, Black said, has helped create a three-dimensional picture by tilting a two-dimensional sample at different angles in the microscope. “He had already made great strides in improving the speed with which this could be done,” Black said. “He’s also improved the process to the point where you don’t have to be a super expert to do it anymore.”

By slowing the reaction in the nickel-cobalt catalyst down and studying how it forms, Xin uncovered that the shell is not solid: It has pinholes. Once those small holes form, the oxygen infiltrates the pores. The process repeats itself, as shells form, then break up, then oxygen forms another shell, which breaks up, until the process leads to a spherically stacked collection of Swiss cheese structures. The process is ready for industrial-scale applications, Xin said, because the whole synthesis involves putting the elements into a furnace and baking it. While this could have applications in fuel cells, the catalyst still awaits a breakthrough technology with alkaline fuel cells.

The technological breakthrough Xin awaits is an alkaline membrane that can conduct a hydroxyl group. “We are definitely doing research for the future,” he said. “We’re still awaiting the essential element, which is the ionic conductive membrane, to become a technologically mature product.” Xin isn’t focused on creating that membrane, which is a task for organic chemists. Instead, his main focus is on inorganic materials.

As a member of the BNL staff at the Center for Functional Nanomaterials, which is a facility that provides technical support to other scientists, Xin spends half of his time with other researchers on the TEM and half of his time on his own research. “We really have been fortunate to have found someone like [Xin] who wants to excel in both sides of his mission,” Black said “Someone as talented as [Xin], who is very smart with big ideas and increasingly ambitious in terms of what he wants to accomplish for himself … checks his ego at the door and he helps others accomplish their goals.” To improve his ability as a colleague, Xin reads about what the users of the TEM are doing and talks with them about their work.

Xin has been working at BNL for over three years. When he’s not in the lab, Xin enjoys traveling to snorkel in the U.S. Virgin Islands, including his favorite destination, St. John. A skier, Xin’s favorite winter recreational mountain is Lake Placid. Xin grew up in Beijing, where his father is a professor in a business school and his mother is an engineer. He appreciates the opportunity to engage in a broad universe of fields through the work he does at BNL and  appreciates the scientific partnerships he’s formed. “My primary focus is on creating novel microscope techniques that can advance the electron microscopy field,” he explained. “I apply them to a variety of materials projects.” Xin estimates that half of his materials application projects come from collaborators.