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Daniel Dunaief

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

By Daniel Dunaief

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Benjamin Martin with his son Calvin. Photo by Richard Row

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

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

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

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

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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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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.

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By Daniel Dunaief

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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.

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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.”

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From left, David Tuveson with Kerri Kaplan, the executive director and chief operating officer of the Lustgarten Foundation, and Sung Poblete, the CEO of Stand Up to Cancer. Photo courtesy of the Lustgarten Foundation

By Daniel Dunaief

Even as David Tuveson was recently fishing for tautog for dinner, he conducted conference calls on a cellphone while watching the clock before an afternoon meeting. A professor at Cold Spring Harbor Laboratory and a world-renowned expert in pancreatic cancer, Tuveson describes the research of some of the students in his laboratory as having considerable bait in the water.

The director of research for the Lustgarten Foundation, Tuveson recently assumed greater responsibility for a larger boat, when he was named director of the Cancer Center at Cold Spring Harbor Laboratory, taking over a role the lab’s president Bruce Stillman held for 25 years. The Cancer Center, which is one part of CSHL, will be in “great hands since Dave Tuveson has wide respect int he cancer community because of his research accomplishments and his talents in leading others,” Stillman explained in an email.

Stillman, who will continue to run his own lab and serve as the President and CEO of CSHL, described Tuveson as a “thought leader” and a “great scientist.” Tuveson and his team of 20 in his laboratory are approaching pancreatic cancer in several directions. They are searching for biomarkers for early detection, developing and testing drugs that preferentially target cancer cells and seeking to uncover the molecular pathways that turn a mutated gene, inflammation, or an illness into a tumor.

Tuveson, who has MD and PhD degrees, focuses on finding ways to use science to help patients. He will continue the Cancer Center’s mission to understand the fundamental causes of the disease, while adding some new strategies. He plans to develop nutrition and metabolism as new areas for the Cancer Center and will recruit “ a few outstanding faculty,” he explained in an email.

CSHL will also expand its skills in immunology and chemistry. Tuveson has dedicated himself and his laboratory to taking innovative approaches to a disease that had received only one-half of 1 percent of the National Cancer Institute’s annual research budget in 1999. That is up to 2 percent today, according to the Lustgarten Foundation, which is the largest private funder of pancreatic cancer research.

Tuveson and his team have become leaders in the developing field of organoids. By taking cells from a tumor or cyst, scientists can produce a smaller copy of the tumor from inside a partial, reproduced patient pancreas. The painstaking work enables researchers to look for the specific type of tumor in a patient, while it also provides a model for testing drugs that might treat the cancer. The technique of growing organoids has become so refined that researchers can create a structure that’s a mix of normal, healthy cells blended with the tumor.

Scientists can then take the resulting structure, called a chimera, and test the effectiveness of therapies in destroying cancers, while monitoring the side effects on healthy cells. Stillman believes Tuveson’s work with pancreas cancer organoids “is at the cutting edge of research in this area.” Tuveson’s lab is using organoids to study what Tuveson, for whom metaphors roll off the tongue as often as characters break into song in Disney movies, describes as kelp-like projections. Each cell has parts that project out from the membrane. His staff is looking for changes in the kelp.

Tuveson is encouraged by work that might help find a subtle protein shift, or changes in the structure of the kelp, as a telltale sign about the type of tumor a patient who is otherwise asymptomatic might have. Doctors might one day screen for these during annual physical exams. Other scientists are so interested in the potential benefits of these organoids that they are attending a training session in Tuveson’s lab that started early this month.

A post doctoral candidate in Tuveson’s lab, Christine Chio, is studying how reactive oxygen affects the growth and stability of cancer. In general, medical professionals have recommended antioxidants to protect health and prevent disease. In pancreatic cancer, however, antioxidants are necessary to keep cancer cells alive. An abundance of reactive oxygen can cause cancer cells to shut down.

“The irony is that cancer cells make their own anti-oxidants and are very sensitive to reactive oxygen — thus we use reactive oxygen to kill cancer cells,” Tuveson explained. Chio, Darryl Pappin, a research professor at CSHL, and several other scientists published their work this summer, in which they identified protein translation as the pathway protected from reactive oxygen species in cancer cells.

At the same time that Tuveson is overseeing the work searching for biomarkers and treatments in his lab, he is also encouraging other research efforts through his work with the Lustgarten Foundation. Started in 1998 when former Cablevision executive Marc Lustgarten developed pancreatic cancer, the Foundation invested $19.4 million in 2015 to pancreatic cancer research and is projected to invest $21 million in 2016.

The mission of the Foundation is to advance research related to the diagnosis, treatment and cure of pancreatic cancer. It also offers patient advice, information and a sense of community through events. Indeed, recently, as a part of a phase 2 clinical trial at Johns Hopkins Kimmel Center, the Foundation offered to provide a free genetic test for microsatellite instability, or MSI, to anyone who might benefit from it as a part of a diagnosis and treatment. MSI occurs in about 2 percent of pancreatic cancer patients. Those with this genetic characteristic responded to a particular type of treatment, called pembrolizumab. The study is still seeking to increase enrollment.

The Foundation is encouraged by the progress scientists like Tuveson have made. “We are hopeful about the future because we know that we have the most talented cancer researchers working on this devastating disease,” Kerri Kaplan, the President and Chief Operating Officer at the Lustgarten Foundation, explained in an email. “We are particularly optimistic about the organoid project and the implications it has for more effective treatments and the work being done on our ‘earlier’ detection program.”

Still, Tuveson and the Foundation, which received donations from 62,000 people in 2015, realize there’s a long way to go. “Pancreatic cancer is an incredibly complex and difficult disease which is why we need to stay focused on funding the most promising research,” Kaplan said.

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Above, Shyamalika Gopalan. The image on the screen shows methylation levels with age. Photo by Casey Youngflesh

By Daniel Dunaief

The Museum of Natural History in New York City features a slice of a 1,400-year-old sequoia tree that was cut down in California in 1891. The cross section of the tree offers a testament to history on its inside. That’s where the tree rings that grow every year mark the passing of another year. As it turns out, humans have something in common with trees. While people may not have rings in bones that an observer can see, they do have age-related changes in their genetic material, or DNA.

Human genes go through a process called methylation in which a methyl group comprised of a carbon and three hydrogens attaches to DNA. Methylation upstream of a gene generally reduces transcription, or the copying of that gene into messenger RNA that can then begin the process of building proteins.

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Shyamalika Gopalan demonstrates how she prepares to extract DNA. Photo by Casey Youngflesh

Using broad time-based methylation changes, Shyamalika Gopalan, who is earning her doctorate at Stony Brook University in the Department of Ecology and Evolution, recently received a three-year grant from the Department of Justice to refine an understanding of methylation and aging. The DOJ would like to use this kind of analysis to gather more information from a scene at which the remaining clues include DNA that isn’t in one of its databases.

Gopalan isn’t the first scientist to study genetic methylation and aging. Other scientists have used blood, saliva and other tissues. She is starting with one type of tissue in the bone. “I’m trying to make” the analysis “more specific to bones,” she said. She doesn’t know how much variation she will find in the age-related methylation patterns depending on ethnicity and lifestyle. “It does appear that some sites are remarkably ‘clock-like,’” she said. “It is these types of sites I’m hoping to find and use in my research.”

Gopalan explained that millions of sites can be methylated. She’s hoping to hone in on those that act more like a clock and that change in a linear manner with time. She’s not sure how many sites she’ll use and said some changes in methylation involve removing methyl groups. “Some methylation increases and some decreases,” she said. “If you know the pattern with age at any site, you can start to build an estimate from those.”

Methylation occurs with age for several possible reasons. “A major theory for these changes in methylation level with age is that the epigenetic patterns are drifting from the optimum,” she said. “This may explain some, or even most, of the changes we observe, but I don’t think it is universally true for all sites in the genome.” Still, there probably is a biologically relevant reason why some of these sites are changing, she suggested.

Gopalan said we know that these methylation patterns are crucial in early development, from conception to birth and she suggested it probably doesn’t completely stop changing there. Some sites are probably regulated throughout life.

Gopalan is hoping to have the bone data prepared by this summer and then believes she’ll be able to get methylation types and start working on a computer algorithm to build a predictor for the next year. After her initial work, she will also shift to saliva and blood.

Like a scene from “Law & Order” or other crime shows, the DNA methylation test may be another clue for police officers or prosecutors to use to rule in or out potential suspects from a crime scene where DNA, but not a driver’s license, is left behind. If the genetic material is not in a database, “you could build a profile and it could be useful for narrowing down suspects,” Gopalan said. At this point, she is taking data for people of age classes but with different ethnicities and lifestyles and comparing them to people of a different age with a similar range of backgrounds and lifestyles.

Gopalan is using samples from medical schools around the New York area, borrowing from anatomy departments where people have donated their bodies to research or teaching. More broadly, she is interested in studying diverse populations, especially in Africa. She has worked with her thesis advisor Brenna Henn, exploring methylation from two different populations. These are the ‡Khomani San of South Africa and the Baka of Cameroon.

Gopalan was interested in working with methylation as a biomarker for aging when she came across this funding opportunity from the DOJ. “It was a good fit for what I had already been studying,” she said, adding that she hopes this method will be used in the future in forensics to assist in criminal investigations.

Krishna Veeramah, an assistant professor of primate genomics at Stony Brook and the chair of her thesis committee, described Gopalan as an “intellectually engaged student who is always eager to absorb information.” Veeramah explained in an email that he thinks “there is scope for this work to transition from basic research” to an application “in criminal forensics and related areas. It will certainly require more work and testing.”

Gopalan has been at SBU for over three years. She lives in Crown Heights, Brooklyn, and commutes about 90 minutes each way most days. She enjoys the beaches, farms, apple picking and the natural beauty of the area. Gopalan would like to continue to perform research after she earns her doctorate, whether that’s with a company, a research institution or with a university. She is excited about extracting and working with DNA, particularly from archeological sites. These samples “come from a field and, once you dust them off, it makes it personal. This is a part of a story.”

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Shinjae Yoo with his son Erum

By Daniel Dunaief

He works with clouds, solar radiation and nanoparticles, just to name a few. The subjects Shinjae Yoo, a computational scientist at Brookhaven National Laboratory, tackles span a broad range of arenas, primarily because his focus is using large pieces of information and making sense of them.

Yoo helps refine and make sense of searches. He develops big data streaming algorithms that can apply to any domain where data scalability issues arise. Integrating text analysis with social network analysis, Yoo did his doctoral research at Carnegie Mellon University, where he also earned a master’s degree, on creating systems that helped prioritize these electronic messages.

“If you are [traveling and] in the airport, before you get into your plane, you want to check your email and you don’t have much time,” he said. While this isn’t the main research work he is doing at the lab, this is the type of application for his work. Yoo developed his technical background on machine learning when he was at Carnegie Mellon. He said he continues to learn, improve and develop machine learning methods in various science domains. By using a statistical method that combines computational science skills, statistics and applied math, he can offer a comprehensive and, in some cases, rapid analysis of information.

Colleagues and collaborators suggested Yoo has made an impact with his work in a wide range of fields. His “contribution is not only in the academic field, but also means a lot on the industrial and academic field,” Hao Huang, a machine learning scientist at GE Global Research, wrote in an email. “He always focuses on making good use of data mining and machine learning theory on real world [areas] such as biology, renewable energy and [in the] material science domain.”

Yoo explained how a plant biologist can do stress conditioning for a plant with one goal in mind. That scientist can collect data over the course of 20 years and then they can “crunch the data, but they can’t always analyze it,” which might be too unwieldy for a bench scientist to handle. Using research from numerous experiments, scientists can study the data, which can provide a new hypothesis. Exploring the information in greater detail, and with increased samples, can also lead to suggestions for the best way to design future experiments.

Yoo said he can come to the scientist and use machine learning to help “solve their science data problem,” giving the researchers a clearer understanding of the broad range of information they collected. “Nowadays, generated data is very easy,” but understanding and interpreting that information presents bigger challenges. Take the National Synchrotron Light Source II at BNL. The $912 million facility, which went live online earlier this year, holds considerable promise for future research. It can look at the molecules in a battery as the battery is functioning, offering a better understanding of why some batteries last considerably longer than others. It can also offer a look at the molecular intermediaries in biochemical reactions, offering a clearer and detailed picture of the steps in processes that might have relevance for disease, drug interactions or even the creation of biological products like shells. He usually helps automate data analytics or bring new hypotheses to scientists, Yoo said. One of the many challenges in experiments at facilities like the NSLS II and the Center for Functional Nanomaterials, also at BNL, is managing the enormous flow of information that comes through these experiments.

Indeed, at the CFN, the transmission electron microscopy generates 3 gigabytes per second for the image stream. Using streaming analysis, he can provide an approximate understanding of the information. Yoo received a $1.9 million, three-year Advanced Scientific Computer Research grant this year. The grant is a joint proposal for which Yoo is the principal investigator. This grant, which launched this September, is about high-performance computing enabled machine learning for spatio-temporal data analysis. The primary application, he said, is in climate. He plans to extend it to other data later, including, possibly for NSLS II experiments.

Yoo finds collaborators through emails, phone calls, seminars or anywhere he meets other researchers. Huang, who started working with Yoo in 2010 when Huang was a doctoral candidate at Stony Brook, appreciates Yoo’s passion for his work. Yoo is “dedicated to his research,” Huang explained. “When we [ran] our proposed methods and got results that [were] better than any of the existing work, he was never satisfied and [was] always trying to further explore to get even better performance.”

When he works with collaborators in many disparate fields, he has found that the fundamental data analysis methodologies are similar. He needs to do some customization and varied preprocessing steps. There are also domain-specific terms. When Yoo came to BNL seven years ago, some of his scientific colleagues around the country were not eager to embrace his approach to sorting and understanding large pools of data. Now, he said other researchers have heard about machine learning and what artificial intelligence can do and they are eager to “apply those methods and publish new papers.”

Born and raised in South Korea, Yoo is married to Hayan Lee, who earned her PhD at Stony Brook and studies computational biology and specializes in genome assembly. They have a four-year old son, Erum. Yoo calls his son “his great joy” and said he “gives me a lot of happiness. Hanging around my son is a great gift.”

When Yoo was entering college in South Korea, he said his father, who had worked at the National Institute of Forest Science, played an important role. After his father consulted with people about different fields, he suggested Yoo choose computer science over chemistry, which would have been his first choice. “He concluded that computer science would be a new field that would have a great future, which is true, and I appreciate my dad’s suggestion,” Yoo said.

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Dr. Hal Walker, co-director of the New York State Center for Clean Water Technology, speaks during a symposium at Stony Brook University Thursday, June 23, 2016. Photo by Barry Sloan

By Daniel Dunaief

Water, water everywhere and Harold “Hal” Walker is making sure there’s more than a few drops on Long Island to drink. The head of the new Department of Civil Engineering at Stony Brook is one of two co-directors of the Center for Clean Water Technology. The center received a $5 million commitment from New York State to pilot test a variety of ways to remove contaminants from drinking water.

“The center will be working with water authorities and water utilities to do pilot testing of new technology to deal with emerging contaminants,” Walker said. “One goal of the testing will be to collect information needed to assess new technologies and, if they are effective, to get them approved so they can be used by water utilities.”

Contaminants the center will explore include 1,4-dioxane and perfluorinated compounds, which have “turned up in some regions of Long Island,” Christopher Gobler, the co-director of the center and an associate dean for research and professor at the School of Marine and Atmospheric Sciences, explained in an email.

’One lesson we have learned is that it is critically important to protect the environment, since the environment serves as a natural buffer to these large storms.’ — Harold Walker

The technologies the center will test likely include novel membrane processes, advanced oxidation, novel absorbents and advanced oxidation processes. The center will explore “how these compounds are removed in conventional drinking water treatments processes,” Walker said. “If they are not removed sufficiently, what do novel technologies use and are they ready for the pilot stage?” Walker acknowledges that staying ahead of the curve in being prepared to protect drinking water requires an awareness of numerous new compounds that are a part of modern manufacturing.

Gobler said the center’s findings would be made public. New York State had previously committed $3.5 million from the Environmental Protection Fund to support the center. With an additional $5 million in funding, the center will develop new technologies to improve drinking water and wastewater quality on Long Island, according to the State Department of Environmental Protection.

The center was formed originally to focus on innovative alternative individual onsite treatment systems for reduction of nitrogen and pathogens. That was broadened this year to focus on the impact of emerging contaminants on water supplies, a representative from the DEC explained in an email.

Walker has built an expertise in developing and applying membrane processes for drinking and wastewater. At Ohio State University, where he worked from 1996 until 2012, when he came to Stony Brook, he spent considerable time analyzing drinking water in the Great Lakes. Gobler appreciates Walker’s expertise.“

He has worked with many federal and state agencies on these topics across the United States,” Gobler explained. “He is also well-versed in wastewater treatment technologies.”

Jennifer Garvey, the associate director for the center, meets with Garvey and Walker at least once a week. She also connects weekly for a call or meeting to discuss administrative and strategic issues. Walker is “at the leading edge of water treatment approaches and he understands where opportunities and obstacles lie,” Garvey said. The center has a sense of urgency about the work because “there is such a clear and immense need for wastewater infrastructure improvements,” she continued. The targeted and strategic work emphasizes near-term solutions. A leading focus is a nonproprietary passive system known as a nitrogen removing biofilter that they will be piloting in Suffolk County soon. “Our hope is that we can make systems available for widespread deployment within the next two to three years,” she said.

Apart from his work at the center, which Walker estimates takes about a third of his time, he is also a professor and the founding chair of the Department of Civil Engineering, which conferred bachelor’s degrees on its inaugural 13 undergraduate students this summer. Those students have all found engineering jobs within their field of interest or continued to pursue additional schooling. The civil engineering department has 10 faculty and is at the end of the first phase of its growth and development, Walker said.

Phase II will include building out the faculty and staff, developing new research and teaching labs and enhancing the recently approved master’s of science and doctoral programs in civil engineering, Walker explained. Resiliency of the coastal communities is a major thrust of his department. He said he recently hired a number of faculty in this area and launched an Advanced Graduate Certificate in Coastal Zone Management and Engineering in partnership with the School of Marine and Atmospheric Sciences. “One lesson we have learned is that it is critically important to protect the environment, since the environment serves as a natural buffer to these large storms,” he explained.

Apart from water and the resilience of the coastal community, the civil engineering department is also involved in transportation. The department works with Farmingdale State College in a new Infrastructure, Transportation and Security Center. In that effort, the department collaborates with the Department of Computer Science, among others at Stony Brook, to bring new approaches to “improving the efficiency, sustainability and safety of our transportation system.”

For his part, Gobler welcomes the talent and expertise the civil engineering department brings to Stony Brook. “This is a tremendous asset” for Stony Brook, Gobler explained in an email. “Civil engineers solve complex problems and I have found that [Walker] and the people he has hired have the skill set and mind-set to address many environmental problems that are important on Long Island.

A resident of Port Jefferson, Walker lives with his wife Alyssa, who is a writer, and their three children, Abby, 14, Halliway, six, and Northie, who is five. They enjoy visiting the beach and traveling east to go apple and pumpkin picking. A native of Southern California, Walker started surfing at the age of 10. He was a four-year varsity letterman in surfing when he was in high school. He has surfed in Hawaii, Costa Rica, Japan, Portugal and Mexico.

As for the department, he said he feels excited by the responsibility for building only the second civil engineering program in the SUNY system. “I’d like the department to quickly become nationally recognized and be the leading source of expertise for the state on infrastructure issues, especially in the downstate area,” he said.

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