Power of 3

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

By Daniel Dunaief

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

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

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

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

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

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

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

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

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

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

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

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

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

By Daniel Dunaief

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

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

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

Eckard Wimmer in his lab. Photo by Naif Mohammed Almojarthi

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

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

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

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

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

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

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

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

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

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

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

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

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

By Daniel Dunaief

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Huloin Xin. Photo courtesy of Brookhaven National Laboratory

By Daniel Dunaief

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

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

Huloin Xin. Photo courtesy of Brookhaven National Laboratory

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

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

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

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

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

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

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

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

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

By Daniel Dunaief

In medieval times, armies needed to understand the structure of the castles they were about to attack. Enough information could enable a leader to find a weakness and exploit it, giving his troops a plan to take over the castle. Today, researchers use advanced tools to study the molecular structure of everything from tumors to the protein plaques involved in neurodegenerative conditions like Alzheimer’s disease.

Recently, William Van Nostrand and Steven Smith, scientists at Stony Brook University who have worked together for over 10 years, discovered subtle differences in amyloid fibril structures that surround blood vessels and neurons. Many forms of the structures likely have some contributory effect to cognitive declines, although researchers debate the extent of that contribution, Van Nostrand said.

Above, William Van Nostrand completes a triathlon this past September in Lake George. Photo courtesy of William Van Nostrand
Above, William Van Nostrand completes a triathlon this past September in Lake George. Photo courtesy of William Van Nostrand

Amyloid fibrils in plaques in the space between neurons have subunits lined up side by side in a head-to-head manner. Van Nostrand and Smith’s new work, which was published in Nature Communications, showed that vascular amyloid subunits, which are on the vessel’s surface, have a different configuration, lining up side by side in an alternating head-to-toe pattern.

This structural difference generates a new set of questions that might provide insight into ways to diagnose or treat diseases or cognitive declines. The structural difference in the vascular forms may provide a way to determine how they uniquely contribute to cognitive decline, which could have implications for diagnostic and therapeutic intervention.

“We want to know if these different structures cause different responses,” said Van Nostrand, who was the co-lead investigator in the study with Smith and is a professor in the Department of Neurosurgery at Stony Brook. The research came from a close structural analysis of the amyloid buildup in mouse models of the disease. Van Nostrand provided the animal models and did the vascular amyloid isolation, while Smith, a professor and the director of structural biology in the Department of Biochemistry and Cell Biology, conducted the structural study.

“The more we understand about how these peptides assemble (and which components and structural motifs actually are toxic to neurons), the easier it is to target” the problem, Smith explained in an email. While the mouse models the scientists studied may have some differences from the human forms of the disease, Van Nostrand said the group also conducted some preliminary studies that showed that vascular amyloid from human vessels has the same structure as the vascular amyloid in isolated vessels from the mice.

Van Nostrand and Smith have “investigated the structure of vascular amyloid in one case of a transgenic mouse and from vessels isolated from the brain of one human patient that had spontaneous cerebral amyloid angiopathy,” Smith said. “In both cases, the structure was anti-parallel, which provides some confidence when we start investigating additional mouse and human samples, we will also find the structure is anti-parallel.”

Van Nostrand’s lab studies pathogenic mechanisms in neurodegenerative diseases, including cerebral amyloid angiopathy. In Alzheimer’s disease, patients have these amyloid or protein plaques around neurons. In about 90 percent of these, people also have protein buildup around blood vessels, where the amount can vary.

Amyloid plaques on the surface of blood vessels are “a lot more common than previously thought,” Van Nostrand said. The consequences of these amyloid fibrils on blood vessels can affect other conditions and treatments for medical challenges including an ischemic stroke. Typically, doctors can prescribe a tissue plasminogen activator. While the drug works to break up the blood clot in the brain, it can cause amyloid blood vessels, if they are present, to bleed, which is a serious side effect.

It would be particularly helpful for doctors and their patients if they knew with certainty before doctors gave any drugs whether the patient had any of these plaques around their blood vessels. The current state of the art in searching for these plaques around blood vessels is to look for any signs of bleeding.

Van Nostrand and Smith are searching for biomarkers that could indicate the presence of specific types of amyloids. “If you had a probe that would recognize a structure, can you also use that for imaging?” Van Nostrand asked. Such a probe might be able to distinguish between the parallel and anti-parallel orientation of the proteins in the plaques.

Van Nostrand said there are rare mutations that create blood vessel amyloids, without the plaque between the neurons. People with only blood vessel amyloids have cognitive impairments, Van Nostrand said, but it’s not the same as Alzheimer’s pathology. In addition to partnering with Smith, Van Nostrand works with Lisa Miller, a biophysical chemist at Brookhaven National Laboratory and collaborators in the Netherlands.

A resident of Poquott, Van Nostrand competes in triathlons and iron man events. During the offseason, when the weather isn’t particularly warm, he still does some training. Van Nostrand’s oldest son, Joffrey, who earned his undergraduate degree at Stony Brook, graduated from law school and is now working at a law firm in Wisconsin. His younger son, Kellen, is applying to graduate school to study psychology. Van Nostrand has an 11-year old daughter, Waela, with his wife Judianne Davis. Waela has done two triathlons and “puts me to shame in 100 yards swimming,” Van Nostrand proudly confessed.

As for his work, Van Nostrand, Smith and their collaborators are focused on understanding how to exploit any differences in the plaques, so they can make progress in the battle against neurodegenerative diseases. “We are interested in understanding structure and pathological functions” of different states of the subunits of amyloid fibrils, Van Nostrand said.

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.

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.

gopalanlab2
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.”

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.

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.

Krishna Veeramah. Photo by Dean Bobo

By Daniel Dunaief

People have left all kinds of signs about their lives from hundreds and even thousands of years ago. In addition to artifacts that provide raw material for archeologists, anthropologists and historians, they also left something modern science can explore: their genes.

Genetic information locked inside their bones can add to the dialogue by providing details about what regions people might have come from and when they arrived. A group that includes Krishna Veeramah, an assistant professor of primate genomics at Stony Brook University, is using genetic information, combined with archeological evidence, to gain a better understanding of the events in Europe immediately after the fall of the Roman Empire, between the fifth and sixth centuries.

“We want to test questions that integrate historical and biological information,” said Veeramah, who is working with a multinational team of scientists. “We want to integrate archeological information.”

This is a time period in which there is some disagreement among historians about what happened after the fall of the Roman Empire. Patrick Geary, the principal investigator on a project that traces early medieval population movements through genomic research, said that this period fundamentally changed not only the demographic makeup of the populations but also the social and political constellation of Europe. These scientists are hoping to contribute their analysis of the genetic material of 1,200 people from several cemeteries to a discussion of the history of the continent.

So, how does this work? Paleogenomic data offers information from hundreds of thousands to millions of positions along the genome, which are called markers or single-nucleotide polymorphisms. Looking at the markers in total, researchers can identify small but systematic genetic differences between groups. They hope to determine where an individual’s ancestors are from based on the bones they are studying. They can only come to these conclusions, Veeramah explained, once they have sampled large numbers of people from different geographic areas during that time period. The genetic differences he is seeing are extremely small. He uses enormous pools of data that can allow him to explore subtle patterns, which emerge at the group level.

While the notion of using the genetic code to contribute information to discussions about the movement of groups of people has its proponents and practitioners, Geary and Veeramah recognize the skepticism, alarm and misdirection that comes from exploring subtle genetic differences among various groups of people. “The application of genetics to the human past is dark,” Geary said, pointing to eugenics discussions. “That’s understandable. We are emphatically opposed to such previous misuses of genetic research.” Some scientists, Geary said, are also suggesting that genetic studies will replace manuscripts or other clues. “We need all types of information,” Geary said.

Indeed, in a cemetery in Hungary that contained about 45 graves, Veeramah is studying genetic differences between two graves that are oriented in another direction from the other adult-sized graves. These two graves don’t contain any grave goods and appear to have different construction. The initial genomic analysis of a subset of individuals suggest they have a genetic profile that is different from other members of the cemetery and may show more of a connection to modern people from southern Europe rather than northern and central Europe, like the rest of the samples. The way these two graves were arranged offers intriguing possibilities, Veeramah said. This may suggest that these individuals had a distinct biological identity, which could impact some aspects of their social identity. To reach any conclusions, he hopes to collect more data from more individuals.

Geary suggested the kind of work he and Veeramah are doing, along with partners in other countries, will offer insight into the different paths of men and women. When paleogenomics first arrived as a discipline, historians were slow to embrace it. At the 2008 American Historical Association’s annual meeting, Geary gave a talk at which about 10 people attended. In January, at the 2017 American Historical Association meeting in Denver, Veeramah will discuss how a study of the Lombards offers a framework for integrating history, archeology and genomics. The president of the American Historical Association invited Veeramah and has publicized the talk as a presidential panel.

“I do believe that paleogenomics has become an important aspect of archeological work, and that the newly developed procedures for sequencing and analyzing genetic material adds a whole new dimension to work on archeological sites,” Patrick Manning, the president of the AHA and a professor of world history at the University of Pittsburgh, wrote in an email. Veeramah’s “work on the Lombards addresses an important issue in the Germanic migrations throughout Europe, long debated and now with important new information.”

Veeramah arrived at Stony Brook University in 2014 and lives in Sound Beach. He grew up outside London in Dartford and attended the same secondary school as Mick Jagger. While he likes some of the Rolling Stones songs, he’s more of a Dizzee Rascal fan. Veeramah plans to have a lab installed by next summer, when he hopes to analyze bones from archeological sites shipped from Europe.

In the meantime, he will continue to analyze genetic information coming from partners in Europe. While Veeramah and others in the field have published papers in prestigious journals like the Proceedings of the National Academy of Sciences and Science, they have struggled to receive funding from American funding agencies at the same level as their European counterparts.

“It is somewhat surprising how far behind the U.S. has gotten in this area,” Veeramah said. European grants can be more adaptable and can put more value on multidisciplinary work. “This is a systematic issue for U.S. funding. I hope it will be addressed soon.”