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Daniel Dunaief

Beetles, which thrive in warmer temperatures, are threatening pine trees

Residents from Cutchogue work together to place sand bags at the edge of the Salt Air Farm before Hurricane Sandy in 2012. Photo by Prudence Heston

While surrounded by salt water, Long Island is in the midst of a drought that is heading into its third year. Amid a trend towards global warming, the New York State Department of Environmental Conservation sent a letter to water district superintendents throughout Suffolk and Nassau County to ask them to lower their water consumption by 15 percent in the next three to four years.

“The primary area that is ripe for reduction is summertime watering,” said Bill Fonda, a spokesman for the DEC. The department has asked the water districts to reduce consumption, but it’s up to the districts to determine how they will reach those goals, he said.

The letter, written by Tony Leung, the regional water engineer, indicated that “results for 2015 show both Nassau and Suffolk County have exceeded the safe yield as cited in the 1986 Long Island Groundwater Management Program,” and that “a concerted effort is needed to reduce peak season water demand.”

The letter, which doesn’t cite global warming, indicates that salt water intrusion, contaminant plumes migration, salt water upconing and competing demand have raised concerns about a need to reduce peak season water demand.

Observers suggested the demand was likely rising for a host of reasons, including increased use of underground irrigation systems and a rise in the population of Long Island.

Water experts welcomed the DEC’s initiative, which is one of many steps Long Islanders can and are taking to respond to a changing environment.

“Most people have no clue how much water they use…They get their water bill, it is what it is, and then they write a check and send it in.”

— Sarah Meyland

Sarah Meyland, the director of the Center for Water Resources Management and associate professor at the New York Institute of Technology, commended the DEC for asserting control over water withdrawals.

“Most people have no clue how much water they use,” Meyland said. “They get their water bill, it is what it is, and then they write a check and send it in.”

She admitted changing consumer behavior will be challenging.

The first step in ensuring water suppliers meet this request, Meyland suggested, is to inform the public about the need for less water use, particularly during the summer months. One possible solution is for irrigation systems that turn off automatically after a rainstorm.

The change in climate has posed a threat to trees that commonly grow on Long Island.

Pine trees have faced an invasion from the southern pine beetle, which extended its range onto Long Island in 2014 and is now a pest that requires routine managing and monitoring.

Long the scourge of pine trees in southern states, the pine beetle, which is about the size of a grain of rice, has found Long Island’s warmer climate to its liking.

“We’re assuming either [Hurricane] Irene or Sandy brought it in,” said John Wernet, a supervising forester at the DEC. “Because it’s getting warmer, the beetle has been able to survive farther north than they have historically.”

Forestry professionals in the south have waged a battle against the beetle for years, trying to reduce the economic damage to the timber market. On Long Island, Wernet said, they threaten to reduce or destroy the rare Pine Barrens ecosystem.

The beetle can have three or four generations in a year and each generation can produce thousands of young.

The first step relies on surveying trees to find evidence of an infestation. Where they discover these unwanted pests, they cut down trees and score the bark, which creates an inhospitable environment for the beetle.

“If left alone, the beetle is like a wildfire and will keep going,” Wernet said. Without direct action, that would be bad news for the pine warbler, a yellow bird that lives near the tops of pine trees, he said.

Wernet added Long Island’s drought also increases the risk of
wildfires.

Farmers, meanwhile, have had to contend with warmer winters that trick their crops into growing too soon while also handling the curveballs created by unexpected cold snaps, frosts, and the occasional nor’easter.

Dan Heston and Tom Wickham survey waters that entered Salt Air Farm after Hurricane Sandy. Photo by Prudence Heston

Last year, the colored hydrangeas of Salt Air Farm in Cutchogue budded early amid warmer temperatures in March, only to perish amid two eight-degree nights.

“We lost [thousands of dollars] worth of hydrangeas in two nights,” said Dan Heston, who works on the farm with his wife Prudence, whose family has been farming on Long Island for 11 generations. “Our whole colored hydrangea season was done.”

Heston said he’s been a skeptic of climate change, but suggested he can see that there’s something happening with the climate on Long Island, including the destructive force of Hurricane Sandy, which flooded areas that were never flooded during large storms before.

“I think the climate is shifting on Long Island,” Prudence Heston explained in an email. “Farmers are constantly having to adapt to protect their crops. In the end, pretty much every adaptation a farmer makes boils down to climate.”

Changes on Long Island, however, haven’t all been for the worse. Warmer weather has allowed some residents to grow crops people don’t typically associate with Long Island, such as apricots and figs. For three generations, Heston’s family has grown apricots.

Other Long Islanders have attempted to grow figs, which are even more sensitive to Long Island winters, Heston said. This was not an economically viable option, as each plant required individual wrapping to survive. That hasn’t stopped some from trying.

“People are now finding our winters to be warm enough to make [figs] a fun back yard plant,” Prudence Heston said.

In other positive developments, the Long Island Sound has had a reduction in hypoxia — low oxygen conditions — over the last decade, according to Larry Swanson, the interim dean of the School of Marine and Atmospheric Sciences at Stony Brook University.

“The state and the Environmental Protection Agency have agreed to a nitrogen reduction program,” Swanson said. “It appears that the decline in nitrogen may be having a positive effect.”

Brookhaven Town took a similar step in 2016.

The town board approved a local law proposed by Supervisor Ed Romaine (R) last summer that established nitrogen protection zones within 500 feet of any body of water on or around Long Island. The zones prohibit new structures or dwellings being built in that range from installing cesspools or septic systems.

Scientists, like those who work out of the Stony Brook University School of Marine and Atmospheric Sciences’ Marine Sciences Center, are constantly asking questions, as the desire grows to find links between correlation and causation. File photo

Researchers often desire more data to help make the distinction between correlation — it rained the last three Tuesdays — and causation — dumping nitrogen into the lake caused the growth of algae that robbed the lake of oxygen.

Scientists don’t like to get ahead of their information, preferring to take the painstaking steps of going that extra mile to control for as many mitigating or confounding variables as they can.

Researchers are often “reluctant to say with certainty that they are correct,” Larry Swanson, the interim dean of the School of Marine and Atmospheric Sciences at Stony Brook University said.

This hesitation to indicate a certain conclusion can raise challenges for politicians, who would like to rely on scientific proof in developing plans for their constituents.

“Policy people want to create a law or regulation that is definitive and will have the desired outcome,” Swanson added.

File photo.

Since he began working in and around Long Island waters in 1960, he started his work collecting data at wetlands around New Haven, and has since studied hypoxia — the process through which oxygen levels are depleted in waterways.

Swanson urges a more extensive collection of data around Long Island.

“I believe we need to monitor the physical environment for changes not just for time series data, such as temperature, but in order to understand how ecological processes are being altered as a consequence of warming,” Swanson said.

Henry Bokuniewicz, a distinguished service professor of oceanography at Stony Brook, said there was a coastline monitoring program in place in 1995 after nor’easters and hurricanes in 1992, but that the effort petered out.

“This should be re-established if [New York State is] serious about coastal impact of shoreline changes,” he said.

Bokuniewicz also suggests measuring and recording waves that are close to shore, and water levels at the ocean coast and interior bays.

Stony Brook had an initiative for additional hires in a cluster for coastal engineering and management, but never completed the hires for budgetary reasons, Bokuniewicz said. “We could do much better with a new generation of scientists dedicated to the Long Island shore,” he said.

Scientists acknowledge that the study of climate change rarely involves establishing the kind of linear connection between action and reaction that turning up the thermostat in a house would provide.

Scientists distinguish between the weather — is it raining today, tomorrow or next week — and the climate — how does March in New York compare to March in North Carolina?

File photo

The climate, generally, remains consistent with a long-term outlook, even if Long Island might experience an unseasonably hot July, an unusually cool September and a heavier-than-normal snowfall in December.

With climate change, scientists collect as much data as they can to determine how the climate is shifting. That presents significant challenges: how do researchers pick data to feed into their models and the patterns to explore?

The broader trend in March could be that spring starts earlier, extending the growing season and creating opportunities for insects, plants or animals to affect the habitat. That could be slightly different this year, amid a cold snap that lasts more than a few days, or in the wake of an unexpected blizzard days before spring.

Indeed, until, and even after there is a scientific consensus, researchers debate long into the night about their interpretations, conclusions and simulation models.

More often than not, scientists crave more information to help them interpret evolving conditions.

“While we know in general why hypoxia will be bad, we can’t really predict it,” Swanson said. “When will it start? How long will it last? This is because we do not understand all the processes — things like the role of bacteria, phytoplankton and the blooming processes and water circulation.”

Science, as it turns out, is often more about collecting more information to ask better questions and developing more precise theories.

As researchers often point out, they can be wrong for the right reasons and right for the wrong ones, all of which, they hope, helps them understand more about the inevitable next set of questions. And, as scientists have offered, it’s a never-ending discussion, as the best answers lead to more questions.

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.”

Image courtesy of Disney Dan Stevens as the Beast and Emma Watson as Belle star in Disney’s ‘Beauty and the Beast.’ Image courtesy of Disney

By Daniel Dunaief

The latest version of “Beauty and the Beast,” which broke box office records when it opened last weekend, offers a visually stunning montage, as one magnificent set blends into the next in a familiar story that, not much of a spoiler here, tracks the well-known story.

The sets, cinematography and songs take center stage in this live-action remake, as Disney spared no expense to make the enchanted castle, the quiet village where every day is like the one before, and the journey through the forest between them as detailed and lavish as the animated version. The script and main actors, including Emma Watson as Belle and Dan Stevens as the Beast, are fine, but not extraordinary.

Disney may not have wanted to tinker too much with a classic film and its well-known dialog, leaving the original script largely unchanged. That is both for the better and the worse, as this current incarnation lacks a novel flavor, a new Disney humor and charm, or the opportunity to explore much more about the characters. There are a few welcome moments when the audience learns more about unfortunate events in Belle and the Beast’s past, but those are short-lived in a film that is over two hours.

Luke Evans does a serviceable job as Gaston, conveying the narcissistic brute who seems more in love with his own reflection than he is with Belle or anyone else. The charm or the irresistibility the villagers feel for him is not evident to Belle or to the audience.

Josh Gad provides welcome comic relief as Gaston’s companion LeFou, fawning over him and calming him down when things don’t go his way. Gad takes his character further than the animated version of LeFou, becoming impish and playful.

Like the Broadway version of the classic animated film “Aladdin” and its “Never Had a Friend Like Me” song, “Beauty and the Beast” somehow equals and, in some ways, exceeds the original film with its “Be Our Guest” feature. While Belle prepares for her meal, the creatures of the castle surround her with food, song and spectacle.

While the script and the characters stay true to the Broadway and animated versions of the story, the visual details truly make the film memorable. The finale in the castle looks like the kind of details an eager bride would include if she had an unlimited budget, with symmetrical floral arrangements, magnificent lighting, perfectly spaced dancers and a cast of characters delighted to share in the space.

For parents, the scenes of peril with the wolves outside the Beast’s castle are familiar and filled with the same kind of potential for danger. Young children will likely be as concerned for the welfare of Belle and the Beast in the wolf scenes of this film as they would be watching the animated version.

The fight scene between the Beast and Gaston also involves some peril, with Gaston displaying a combination of cowardice and villainy. At the same time, the fight scene between the villagers incited by Gaston to battle and the members of the enchanted castle who are defending themselves also contains some of the few moments of humor in a film that otherwise takes its tale and the retelling of it seriously.

Some of the other cast members, including Emma Thompson as Mrs. Potts, have a tough act to follow, repeating familiar phrases and songs from Angela Lansbury. Thompson holds her own, regaling the audience with the lyrics from a tale as old as time.

The three-dimensional version of the film included a few noticeable effects, including when Belle and the Beast engage in a snowball fight. It also adds some depth to the image of the castle and the trek through the woods. The additional expense, however, didn’t seem especially necessary, given an elaborate attention to other visual details.

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.

From left, Catherine Keener, Bradley Whitford, Allison Williams and Daniel Kaluuya in a scene from ‘Get Out,’ now playing at local theaters. Photo courtesy of Universal

By Daniel Dunaief

Race permeates Jordan Peele’s directorial debut “Get Out” so thoroughly that the film is like a battery, with the white people on one side and the African-Americans on the other. Between them, the electricity of an unusual horror film flows with a shocking effect.

The film starts off with the feel of Sidney Poitier’s masterpiece, “Guess Who’s Coming to Dinner,” with Rose Armitage, played by Allison Williams, bringing her African-American boyfriend Chris Washington (Daniel Kaluuya) home to meet her parents. Even though she says he’s the only African-American man she’s dated, she makes it clear that her parents will be totally cool with her choice and that they’ll support the biracial couple. And yet, the film quickly disposes of any notion of a simple meeting between an African-American man and potentially liberal white America.

Daniel Kaluuya in a hypnotic scene from ‘Get Out’. Photo courtesy of Universal

While Chris meets several African-American people around his girlfriend’s parents’ house, each encounter has a Hitchcock quality, with an eerie disconnect that suggests an unexplained distance.

On the other hand, Rose’s parents and her over-the-top creepy brother Jeremy (Caleb Landry Jones), who wants to fight with Chris at dinner, introduce a terrifying blend of personalities. Catherine Keener is at her creepy best, playing Rose’s hypnotist mother Missy while Bradley Whitford as Rose’s father Dean seems on the verge of supporting and attacking Chris at the same time.

Chris’s best friend Rod (Lil Rel Howery), who spends much of the movie talking to Chris by cell phone, threatens to steal the movie. A TSA agent, Rod provides comic relief, infusing the movie with humorous lines that seem straight out of a paranoid playbook, until he seems like the only one who might have a clue about what could be going on at Rose’s house.

The movie is a true horror film, which means there’s gore and an undercurrent of violence. Each scene, which occurs in upstate New York, could easily have been filmed in Salem, Massachusetts, home of mass hysteria and witch trials.

As the movie progresses, Peele gradually reviews details about the Armitage family, and the people who share the upstate neighborhood, that blur the line between mundane and creepy. When the plot unfolds, all the details about how Chris and the audience got there become clear.

The final 20 minutes of the film blend horror, gore, comedy and social satire. Some of the particular details of the plot reside in the willing suspension of disbelief. Thinking through the specifics detracts from the film’s value as entertainment and social commentary.

The audience in the packed theater reacted to the climactic scenes of “Get Out” in a way that would likely please Peele, as they shared the drama of a gruesome experience that strays from customary plot points to shocking drama and horror.

While the film offers a disturbing take on race, it also tells a dramatic story that drives the viewer through to the chilling end. While it’s not Mark Twain’s “Huckleberry Finn,” it does reveal a captivating, literally at times, story that keeps the audience guessing and at times horrified.

The best element of “Get Out” is the balance between horror and comedy, provided primarily by Rod, whose fast-talking, high-pitched responses to situations he senses aren’t what they seem are endearing and amusing.

While “Get Out” offers the audience plenty to ponder after the movie ends, the action and the plot won’t appeal to everyone. It earns its R rating with violence, horror, foul language and dangerous, suspenseful situations. Still, the movie exposes a fresh look at the races, albeit with novel plot devices, and it seemed to satisfy its viewers with unexpected and jarring visuals, music and close-ups.

Above, members of the New York Chapter of The Children’s Heart Foundation present CSHL Research Assistant Professor Michael Ronemus with a $50,000 check from The Children’s Heart Foundation for his recently funded research grant on Feb. 23. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

By Daniel Dunaief

Just before he took a holiday break in December, Michael Ronemus received a welcome surprise. “In the last afternoon before the holidays, I got a call from William Foley. He said, ‘Congratulations,’” recalled Ronemus, a research assistant professor at Cold Spring Harbor Laboratory. “I submitted the application in May and I didn’t know what to expect.”

Foley, the executive director at the Children’s Heart Foundation, was reaching out to Ronemus to let him know he was one of seven researchers — six in North America and one in Europe — to receive funding for his research. Ronemus received a check for $50,000 at a presentation ceremony on Feb. 23.

Scientists are seeking out private foundations more as they search for sources of funding, said Ronemus. The funds will help Ronemus use next-generation sequencing to look closely at 120 families for evidence of copy number variation in their genes.

 

When a person has a different number of copies of a part of a specific gene, that can be a positive, neutral or negative event, depending on the consequence for the individual. Most copy number variations are neutral, which is why people have hundreds of them in their genes. Copy number variations can contribute, however, to de novo mutations, presenting changes in a genetic code that can make the genes of an offspring different from those of his or her parents. If these mutations damage a gene that’s essential for normal development of the heart, they can contribute to congenital heart defects.

Michael Ronemus explains the relevance of his research to the community at the check presentation event on Feb. 23. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

Indeed, the Children’s Heart Foundation has contributed $8.7 million to research, hoping to improve the ability to prevent, diagnose and treat the 40,000 people born each year in the United States with a heart defect. Of the children born with a heart defect, about one in four, has a form of critical congenital heart disease, said Jon Kaltman, the chief in the Heart Development and Structures Diseases Branch of the National Heart, Lung and Blood Institute. That means he or she will most likely require surgery within the first year of life, although most have it within the first month.

At this point, doctors and researchers understand the genetic cause of congenital heart disease for a small percent of people. The work of the Pediatric Cardiac Genomics Consortium hopes to make this true for a larger number of people with a congenital heart defect, Kaltman said.

Knowing the genetics of a patient and his or her family could be “helpful for that family to understand what might have caused the congenital heart disease” said Kaltman, who has been a pediatric cardiologist since 2005. “If that family were to have another child” the genetics could help assess the “risk that a second child will also have a congenital heart defect.”

A greater awareness of the genes involved in heart disease could also provide a guide for the way the defect might react to treatment. “We see patients with identical looking hearts [on an echocardiogram] from different families in which they undergo surgery” and have different reactions, Kaltman said. “One does well and has few complications and the other develops arrhythmias at 15 and heart failure at 25.”

The differences in respones to treatment for those patients may be genetic. “For the patient with the genetic signal for the complicated course, we can do more interventions early on,” Kaltman said, which could include earlier valve replacements or more aggressive arrhythmia surveillance.

Working with Bruce Gelb, a professor in pediatrics and cardiology at Mount Sinai Hospital, Ronemus is focusing on a group of patients with a condition called tetralogy of Fallot. Children with this defect develop a bluish color in their skin and can have trouble breathing when they exercise.

New York Chapter president of the Children’s Heart Foundation Jackie Pecora speaks at the check presentation event. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

Doctors treat people with this condition with open heart surgery, which fixes a hole between the ventricles and opens up a narrowed right ventricular outflow tract. “Early diagnosis can lead to a straightforward procedure and good outcome,” Ronemus said. “If there is any reason to suspect [that a developing fetus has this condition], we’d like to know.”

By studying copy number variation, Gelb and Ronemus can search for signatures or markers in prenatal screening, which doctors can do through amniocentesis or cell-free fetal DNA analysis, which is a noninvasive form of prenatal testing. A definitive diagnosis even before birth could help doctors prepare for quick intervention that could be more effective, Ronemus said. If not diagnosed, a third of the children with the condition die within the first year and 50 percent in the first three years, Ronemus explained. If doctors know a child has the condition, they can take precautions, like have supplementary oxygen or drugs nearby.

Ronemus, who started his career in plant genetics and then became involved in the study of autism, is applying a genetic technique he co-developed at CSHL for copy number variation detection called SMASH. He applied for the Children’s Heart Foundation grant because of a meeting at CSHL with Jackie Pecora, a resident of East Northport, who is New York Chapter president of the Children’s Heart Foundation. The foundation has 11 chapters throughout the country and raises funds through events like the Long Island Congenital Heart Walk, which will take place on May 21 in Sunken Meadow State Park. Ronemus will be an honorary co-chair for the walk.

Foley said Ronemus’ approach is a “unique way” of looking at congenital heart defects. During the medical advisory board’s discussion of which projects to fund “there was a lot of enthusiasm” for this project. Ronemus is the first New York researcher to receive CHF funds since 2009.

A resident of East Meadow, Ronemus lives with his wife Ana Rodriguez-Fernandez, who is an associate professor of microbiology at the NYU School of Medicine. The couple has three children, Martin, 14, Silvia, 12, and Daniel, 11.

Pecora has family experience with congenital heart disease. After she gave birth to twins 18 years ago, doctors discovered that her daughter Chloe had a heart defect that required surgery. Nine days after she was born, Chloe died from an infection. Pecora got involved because of a bumper sticker for another grassroots fundraiser for a baby with the same heart condition as Chloe. That led her to the Children’s Heart Foundation. While the awareness among the public is improving, there’s still a way to go to combat a prevalent condition, Pecora said. “Look at the clock: Every 15 minutes a baby is born with congenital heart disease. People don’t realize the magnitude.”

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.”

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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