Power of 3

Hervé Tiriac during a recent visit to the University of Nebraska Cancer Center. Photo by Dannielle Engel

By Daniel Dunaief

What if doctors could copy human cancers, test drugs on the copies to find the most effective treatment, and then decide on a therapy based on that work?

Hervé Tiriac, a research investigator at Cold Spring Harbor Laboratory, moved an important step closer to that possibility with pancreatic cancer recently.

Tiriac, who works in the Cancer Center Director Dave Tuveson’s lab, used so-called organoids from 66 patients with pancreatic ductal adenocarcinoma tumors. These organoids reacted to chemotherapy in the same way that patients had. 

“This is a huge step forward,” Tiriac said, because of the potential to use organoids to identify the best treatments for patients.

Hervé Tiriac. Photo by Dannielle Engel

Tuveson’s lab has been developing an expertise in growing these organoids from a biopsy of human tumors. The hope throughout the process has been that these models would become an effective tool in understanding the fourth most common type of cancer death in men and women. The survival rate five years after diagnosis is 8 percent, according to the American Cancer Society.

The study, which was published in the journal Cancer Discovery, “shows real promise that the organoids can be used to identify therapies that are active for pancreatic cancer patients,” Tuveson explained in an email. “This may be a meaningful advance for our field and likely will have effects on other cancer types.”

Kerri Kaplan, the president and CEO of the Lustgarten Foundation, which has provided $150 million in financial support to research including in Tuveson’s lab, is pleased with the progress in the field.

“There’s so much momentum,” Kaplan said. “The work is translational and it’s going to make a difference in patients’ lives. We couldn’t ask for a better return on investment.”

Tiriac cautions that, while the work he and his collaborators performed on these organoids provides an important and encouraging sign, the work was not a clinical trial. Instead, the researchers retrospectively analyzed the drug screening data from the organoids and compared them to patient outcomes.

“We were able to show there were parallels,” he said. “That was satisfying and good for the field” as organoids recapitulated outcomes from chemotherapy.

Additionally, Tiriac’s research showed a molecular signature that represents a sensitivity to chemotherapy. A combination of RNA sequences showed patterns that reflected the sensitivity for the two dominant chemotherapeutic treatments. “It was part of the intended goal to try to identify a biomarker,” which would show treatment sensitivity, he said.

While these are promising results and encourage further study, researchers remain cautious about their use in the short term because several technical hurdles remain.

For starters, the cells in the organoids take time to grow. At best right now, researchers can grow them in two to four weeks. Drug testing would take another few weeks.

That is too slow to identify the best first-line treatment for patients with advanced pancreatic cancer, Tiriac explained. “We have to try to see if the organoids could identify these biomarkers that could be used on a much shorter time frame,” he added.

Tuveson’s lab is working on parallel studies to accelerate the growth and miniature the assays. These efforts may reduce the time frame to allow patients to make informed clinical decisions about their specific type of cancer.

As for the RNA signatures, Tiriac believes this is a first step in searching for a biomarker. They could be used in clinical trials as is, but ideally would be refined to the minimal core gene signatures to provide a quick and robust assay. It is faster to screen for a few genes than for hundreds of them. He is studying some of these genes in the lab.

Researchers in Tuveson’s lab will also continue to explore biochemistry and metabolism of the organoids, hoping to gain a better insight into the mechanisms involved in pancreatic cancer.

Going forward, Tiriac suggested that his main goal is to take the gene signatures he published and refine them to the point where they are usable in clinical trials. “I would like to see if we can use the same approach to identify biomarkers for clinical trial agents or targets that may have a greater chance of impact on the patients,” he said.

The research investigator has been working at Tuveson’s lab in Cold Spring Harbor since the summer of 2012.

Tuveson applauded Tiriac’s commitment to the work. Without Tiriac’s dedication, “there would be no Organoid Profiling project,” Tuveson said. “He deserves full credit for this accomplishment.”

Tiriac lives in Huntington Station with his wife Dannielle Engle, who is a postdoctoral researcher in the same lab. He “really enjoyed his time on Long Island,” and suggested that “Cold Spring Harbor has been a fantastic place to work. It’s probably the best institution I’ve worked at so far.”

He appreciates the chance to share the excitement of his work with Engle. “You share a professional passion with your loved one that is beyond the relationship. We’re able to communicate on a scientific level that is very stimulating intellectually.”

Born in Romania, Tiriac moved to France when his family fled communism. He eventually wound up studying in California, where he met Engle.

Tuveson is appreciative of the contributions the tandem has made to his lab and to pancreatic cancer research. 

“Although I could not have imagined their meritorious accomplishments when I interviewed them, [Tiriac and Engle] are rising stars in the cancer research field,” he said. “They will go far in their next chapter, and humanity will benefit.”

Kaplan suggested that this kind of research has enormous potential. “I feel like it’s a new time,” she said. “I feel very different coming into work than I did five years ago.”

From left, Evan Sohn, co-founder of the Sohn Conference Foundation; Benjamin Martin, associate professor at Stony Brook University; and Bill Ackman, co-founder of the Pershing Square Foundation and CEO of Pershing Square Capital Management at an awards dinner. Photo by Melanie Einzig/PSSCRA

By Daniel Dunaief

Up and coming scientists are often stuck in the same position as promising professionals in other fields. To get the funding for research they’d like to do, they need to show results, but to get results, they need funding. Joseph Heller, author of “Catch 22,” would certainly relate.

A New York-based philanthropy called the Pershing Square Sohn Cancer Research Alliance is seeking to fill that gap, providing seven New York scientists with $600,000 each over the course of three years.

In the fifth annual competition, Benjamin Martin, an associate professor in the Department of Biochemistry & Cell Biology at Stony Brook University, won an award for his study of zebrafish models of metastatic cancer. Martin is the first Stony Brook researcher to win the prize.

Working with Assistant Professor David Matus, whose lab is across the hall and whose research team conducts weekly group meetings with Martin’s lab, Martin is able to see in real time the way grafted human tumor cells spread through blood vessels to other organs in the transparent zebrafish.

“It’s been very challenging to understand what process cancer cells are using to metastasize and leave the blood vessels,” said Olivia Tournay Flatto, the president of the Pershing Square Foundation. “With this technology, he can see what’s happening. It’s a really powerful tool.”

The work Martin presented was “really appealing to the whole board, and everybody felt this kind of project” had the potential to bring data and insights about a process researchers hope one day to slow down or stop, said Flatto.

This year, about 60 early-stage investigators applied for an award given specifically to researchers in the New York City area. When he learned that he won, Martin said, “There was some dancing going on in the living room.” He suggested that the award is a “validation” of his research work.

The process of a cancer cell leaving a blood vessel is “basically a black box” in terms of the mechanism, Martin said. It’s one of the least understood aspects of metastasis, he added.

Indeed, a developmental biologist by training, Martin is hoping to discover basics about this cancer-spreading process, such as an understanding of how long it takes for cancer cells to leave blood vessels. The process can take hours, although it’s unclear whether what he’s seen is typical or abnormal.

Martin would like to identify how the cancer cells adhere to the blood vessel walls and how and why they leave once they’ve reached their target.

Metastatic cancer is likely using the same mechanism the immune system uses to travel to the sites of infection, although researchers still need to confirm several aspects of this model.

Moving in involves interactions with white blood cells, including macrophages. With white blood cells, an area of infection or inflammation becomes activated, which triggers a reaction of adhesion molecules called selectins.

By watching a similar transport process in cancer, Martin and Matus can “see things people haven’t seen before” and can explore way to inhibit the process, Martin suggested.

He is hoping to find ways to stop this process, forcing cancer cells to remain in the blood vessels. While he doesn’t know the outcome of a cancer cell’s prolonged stay in the vessel, he predicts it might end up dying after a while. This approach could be combined with other therapies to force the cancer cells to die, while preventing them from spreading.

Through this grant, Martin will also study how drugs or mutations in selectins generate a loss of function in these proteins, which affects the ability of cancers to leave the blood vessel.

Martin plans to use the funds he will receive to hire more postdoctoral researchers and graduate students. He will also purchase additional imaging equipment to enhance the ability to gather information.

Martin appreciates that this kind of research, while promising, doesn’t often receive funding through traditional federal agencies. This type of work is often done on a mouse, which is, like humans, a mammal. The enormous advantage to the zebrafish, however, is that it allows researchers to observe the movement of these cancer cells, which they couldn’t do in the hair-covered rodent, which has opaque tissues.

“There’s a risk that these experiments may not work out as we planned,” Martin said. He is hopeful that the experiments will succeed, but even if they don’t, the researchers will “learn a great deal just from seeing behaviors that have not been observed before.”

Indeed, this is exactly the kind of project the Pershing Square Sohn Cancer Research Alliance seeks to fund. They want scientists to “put forward the riskiest projects,” Flatto said. “We are ready to take a chance” on them.

One of the benefits of securing the funding is that the alliance offers researchers a chance to connect with venture capitalists and commercial efforts. These projects could take 20 years or more to go from the initial concept to a product doctors or scientists could use with human patients.

“We are not necessarily focused on them starting a company,” Flatto said. “We think some of those projects will be able to be translated into something for the patient,” which could be through a diagnosis, prevention or treatment. “This platform is helpful for young investigators to be well positioned to find the right partners,” he added.

Aaron Neiman, the chairman of the Department of Biochemistry & Cell Biology at SBU, suggested that this award was beneficial to his department and the university.

“It definitely helps with the visibility of the department,” Neiman said. The approach Matus and Martin are taking is a “paradigm shift” because it involves tackling cells that aren’t dividing, while many other cancer fighting research focuses on halting cancer cells that are dividing.

Neiman praised the work Martin and Matus are doing, suggesting that “they can see things that they couldn’t see before, and that’s going to create new questions and new ideas,” and that their work creates the opportunity to “find something no one knew about before.”

From left, Shawn Serbin, University of Maryland collaborator Feng Zhao and Ran Meng. Photo by Roger R. Stoutenburgh

By Daniel Dunaief

Not all greenery is the same. From above the Earth, forests recovering after a fire often look the same, depending on the sensing system. An area with bushes and shrubs can appear to have the same characteristics as one with a canopy.

From left, Shawn Serbin, University of Maryland collaborator Feng Zhao and Ran Meng. Photo by Roger R. Stoutenburgh

Working in associate ecologist Shawn Serbin’s laboratory at Brookhaven National Laboratory, Ran Meng, a postdoctoral researcher, recently figured out a way to improve the level of information gained from these remote images, enabling them to distinguish among the different types of growth after a forest fire.

Examining the growth in a pine forest on Long Island after a fire near BNL in 2012, Meng used various spectral properties to get a more accurate idea of how the forest was recovering. Meng and Serbin recently published their results in the journal Remote Sensing of Environment.

“Using our remote sensing analysis, we were able to link detailed ground measurements from [BNL’s Kathy Schwager and Tim Green] and others to better understand how different burn severities can change the recovery patterns of oak and pine species,” Serbin explained in an email. The information Meng and Serbin collected and analyzed can map canopy moisture content and health as well as fuels below the canopy to identify wildfire risk.

The imagery can be used to map the water content or moisture stored in the leaves and vegetation canopies, Serbin explained. LiDAR data can see through the canopy and measure the downed trees and other fuels on the forest floor. This type of analysis can help differentiate the type of growth after a fire without requiring extensive surveys from the ground.  “One of the issues on the ground is that it’s time consuming and expensive,” Serbin said. Remote sensing can “cover a much larger area.”

Assisted by Meng’s background in machine learning, these researchers were able to see a higher resolution signal that provides a more detailed and accurate picture of the vegetation down below. One of the purposes of this work is to help inform forest managers’ decision-making, Serbin added. A forest with a canopy will likely capture and retain more water than one dominated by bushes and shrubs. A canopied forest acts “more like a sponge” in response to precipitation.

A canopied forest can “hold water,” Meng said. If the canopy disappears and changes to shrubs or grass, the forest’s capacity to store water will be damaged. Altering the trees in a forest after a fire can start a “reaction chain.” Without a nearby canopied forest, the water cycle can change, causing more erosion, which could add more sediment to streams.

Serbin recently met with the Central Pine Barrens Commission, the Department of Environmental Conservation and SUNY College of Environmental Science and Forestry, which is based in Syracuse.

Serbin had planned to meet with these groups several years ago to try to build a better relationship between the information the lab was collecting and the pine barrens and ESF to “use the lab as a field research site.”

They discussed ways to use the science to inform management to keep the pine barrens healthy. The timing of the meeting, so soon after the publication of the recent results related to fire damage surveys, was fortuitous.

“It just happens that this work with [Meng] comes out and is highly relevant,” Serbin said. “This is a happy coincidence.” He said he hopes these groups can use this information to feed into a larger model of research collaboration. This work not only provides a clearer picture of how a forest recovers, but also might suggest areas where a controlled burn might benefit the area, minimizing the effect of a more intense fire later on.

“These forests used to burn more often but with less intensity due to the lower fuel loads from more frequent fire,” Serbin explained. Fire suppression efforts, however, have meant that when fires do burn, they occur with higher intensities. “It could be harder to maintain the pine barrens because the fires burn more strongly, which can reduce or destroy the soil seed stock or alter the recovery trajectory in other ways,” he said.

The remote sensing analysis of trees uses shapes, sizes, leaf color and chemistry to explore the fingerprints of specific trees. This could offer researchers and conservationists an opportunity to monitor endangered species or protected habitats.

“We can do even better using platforms like NASA G-LiHT because we can use both the spectral fingerprint as well as unique structural characteristics of different plants” to keep track of protected areas, Serbin explained.

As for what’s next, Serbin said he would like to scale this study up to study larger areas in other fire-prone systems, such as boreal forests in Alaska and Canada. He plans to apply these approaches to develop new forest recovery products that can be used in conjunction with other remote sensing data and field studies to understand forest disturbances, recovery and carbon cycling.

Meng plans to move on in August to work directly with the NASA G-LiHT team. He said he believes this kind of work can also track infestations from beetles or other pests that attack trees or damage forests, adding, “There are some slight changes in spectral patterns following beetle outbreaks.”

A final goal of this project, which admittedly requires considerably more work according to Meng, is to monitor those changes early to enable forest managers to intervene, potentially creating the equivalent of an insect break if they can act soon enough.

Serbin appreciated the work his postdoc contributed to this project, describing Meng as a “dedicated researcher” who had to “sort out what approaches and computational techniques to use in order to effectively characterize” the images.

“[He] persevered and was able to figure out how to analyze these very detailed remote sensing data sets to come up with a new and novel pattern that hadn’t really been seen before,” said Serbin.

Rachel Caston looks at lunar soil simulant JSC1A. Photo by Upasna Thapar

By Daniel Dunaief

It’s the ultimate road trip into the unknown. Space travel holds out the possibility of exploring strange new worlds, boldly going where no one has gone before (to borrow from a popular TV show).

While the excitement of such long-distance journeys inspires people, the National Aeronautics and Space Administration, among other agencies, is funding scientific efforts to ensure that anyone donning a spacesuit and jetting away from the blue planet is prepared for all the challenges to mind and body that await.

Rachel Caston, recently completed her doctorate, which included work at Stony Brook University in the laboratory of Bruce Demple for a project that explored the genetic damage lunar soil simulants have on human lung cells and on mouse brain cells.

Geologist Harrison Schmitt, who was the Apollo 17 lunar module pilot, shared symptoms he described as “lunar hay fever,” which included the types of annoyances people with allergies have to deal with during the spring: sore throat, sneezing and watery eyes.

Using simulated lunar soil because actual soil from the moon is too scarce, Caston found that several different types of soil killed the cell or damaged the cell’s genes, or DNA for both human lung and mouse brain cells.

While there has been considerable research that explores the inflammation response to soil, “there wasn’t any research previously done that I know of [that connected] lunar soil and DNA damage,” said Caston, who was the lead author on research published recently in the American Geophysical Union’s journal GeoHealth.

The moon’s soil becomes electrostatic due to radiation from the sun. Astronauts who walked on the moon, or did various explorations including digging into its surface, brought back some of that dust when it stuck to their space suits.

Caston sought to understand what causes damage to the DNA.

Going into the study, Demple, a professor of pharmacological sciences at SBU, suggested that they expected that the materials most capable of generating free radicals would also be the ones that exerted the greatest damage to the cells and their DNA. While free radicals may play a role, the action of dust simulants is more complex than that created by a single driving force.

Caston looked at the effect of five different types of simulants, which each represented a different aspect of lunar soil. One of the samples came from soil developed to test the ability of rovers to maneuver. Another one came from a lava flow in Colorado.

Demple said that the materials they used lacked space weather, which he suggested was an important feature of lunar soil. The surface of the moon is exposed constantly to solar wind, ultraviolet light and micrometeorites. The researchers mimicked the effect of micrometeorites by crushing the samples to smaller particle sizes, which increased their toxicity.

Farm to table: Caston eats ice cream and pets the cow that provided the milk for her frozen dessert at Cook’s Farm Dairy in Ortonville, Michigan. Photo by Carolyn Walls

In future experiments, the researchers plan to work with colleagues at the Department of Geosciences at SBU, including co-author Joel Hurowitz and other researchers at Brookhaven National Laboratory to mimic solar wind by exposing dust samples to high-energy atoms, which are the main component of solar wind. The scientists expect the treatment would cause the simulants to become more reactive, which they hope to test through experiments.

Caston credits Hurowitz , an assistant professor in the Department of Geosciences, with providing specific samples.

The samples are commonly used simulants for lunar rocks that mimic the chemical and mineral properties of the lunar highlands and the dark mare, Hurowitz explained.

“This has been a really fruitful collaboration between geology and medical science, and we’ll continue working together,” Hurowitz wrote in an email. They plan to look at similar simulants from asteroids and Mars in the future.

NASA has considered engineering solutions to minimize or eliminate astronaut’s exposure to dust. It might be difficult to eliminate all exposure for workers and explorers living some day on the moon for an extended period of time.

“The adherence of the dust to the space suits was a real problem, I think,” suggested Demple, adding that the next steps in this research will involve checking the role of the inflammatory response in the cytotoxicity, testing the effects of space weathering on toxicity and applying to NASA for actual samples of lunar regolith brought back by Apollo astronauts.

It took about two years of preliminary work to develop the methods to get consistency in their results, Demple said, and then another year of conducting research.

In addition to her work on lunar soil, Caston has studied DNA repair pathways in mitochondria. She used her expertise in that area for the DNA damage results they recently reported.

Caston, who is working as a postdoctoral researcher in Demple’s lab, is looking for a longer-term research opportunity either on Long Island or in Michigan, the two places where she’s lived for much of her life.

Caston lives in Smithtown with her husband Robert Caston, a software developer for Northrop Grumman. She earned her bachelor’s degree as well as her doctorate from Stony Brook University.

Her interest in science in general and genetics in particular took root at an early age, when she went with her father Kenneth Salatka, who worked at Parke Davis, a company Pfizer eventually bought. 

On April 23, 1997, she convinced her friend and her identical twin sister to attend a “fun with genetics” event.

Two of the people at her father’s company were using centrifuges to isolate DNA out of blood. “That was the coolest thing I ever saw,” she said. “I wanted to be a geneticist from that point on.” 

Her sister Madeline, who now sells insurance for Allstate, and her friend weren’t similarly impressed.

As for the work she did on lunar soil, Caston said she enjoys discussing the work with other people. “I like that I’m doing a project for NASA,” she said. “I’ve learned quite a bit about space travel.”

From left, Libo Wu, Zhangjie Chen (both are doctoral students on the ARPA-E project), Ya Wang, Xing Zhang (graduated), Muzhaozi Yuan and Jingfan Chen (both are doctoral students on the NSF project). Photo courtesy of Stony Brook University

By Daniel Dunaief

Picture a chalkboard filled with information. It could include everything from the basics — our names and phone numbers, to memories of a hike along the Appalachian Trail, to what we thought the first time we saw our spouse.

Diseases like Alzheimer’s act like erasers, slowly moving around the chalkboard, sometimes leaving traces of the original memories, while other times removing them almost completely. What if the images, lines and words from the chalk could somehow be restored?

Ya Wang with former student Wei Deng at Stony Brook’s Advanced Energy Research and Technology Center. Photo courtesy of SBU

Ya Wang, a mechanical engineering assistant professor at Stony Brook University, is working on a process that can regenerate neurons, which could help with a range of degenerative diseases. She is hoping to develop therapies that might restore neurons by using incredibly small magnetic nanoparticles.

Wang recently received the National Science Foundation Career Award, which is a prestigious prize given to faculty in the early stages of their careers. The award lasts for five years and includes a $500,000 grant.

Wang would like to understand the way small particles can stimulate the brain to rebuild neurons. The award is based on “years of effort,” she said. “I’m happy but not surprised” with the investment in work she believes can help people with Alzheimer’s and Parkinson’s diseases.

“All neuron degeneration diseases will benefit from this study,” Wang said. “We have a large population in New York alone with patients with neuron degeneration diseases.” She hopes the grant will help trigger advancements in medicine and tissue engineering.

Wang’s “work on modeling the dynamic behavior of magnetic nanoparticles within the brain microenvironment would lay the foundation for quantifying the neuron regeneration process,” Jeff Ge, the chairman and professor of mechanical engineering, said in a statement.

Wang said she understands the way neurodegenerative diseases affect people. She has watched her father, who lives in China, manage through Parkinson’s disease for 15 years.

Ge suggested that this approach has real therapeutic potential. “This opens up the exciting new possibility for the development of a new microchip for brain research,” he said.

At this point, Wang has been able to demonstrate the feasibility of neuron regeneration with individual nerve cells. The next step after that would be to work on animal models and, eventually, in a human clinical trial.

That last step is a “long way” off, Wang suggested, as she and others will need to make significant advancements to take this potential therapeutic breakthrough from the cell stage to the clinic. 

She is working with a form of coated iron oxide that is small enough to pass through the incredibly fine protective area of the blood/brain barrier. Without a coating, the iron oxide can be toxic, but with that protective surface, it is “more biofriendly,” she said.

The size of the particles are about 20 nanometers. By contrast, a human hair is 80,000 nanometers thick. These particles use mechanical forces that act on neurons to promote the growth or elongation of axons.

Ya Wang. Photo from SBU

As a part of the NSF award, Wang will have the opportunity to apply some of the funds toward education. She has enjoyed being a mentor to high school students, some of whom have been Siemens Foundation semifinalists. Indeed, her former students have gone on to attend college at Stanford, Harvard and Cal Tech. “I was very happy advising them,” she said. “High school kids are extremely interested in the topic.”

A few months before she scored her NSF award, Wang also won an Advanced Research Projects Agency–Energy award for $1 million from the Department of Energy. In this area, Wang also plans to build on earlier work, developing a smart heating and cooling system that enables a system to direct climate control efforts directly at the occupant or occupants in the room.

Extending on that work, Wang, who will collaborate in this effort with Jon Longtin in the Department of Mechanical Engineering at SBU and Tom Butcher and Rebecca Trojanowski at Brookhaven National Laboratory, is addressing the problem in which the system no longer registers the presence of a person in the room.

Wang has “developed an innovation modification to a simple, inexpensive time-honored position sensor, but that suffers from requiring that something be moving in order to detect motion,” Longtin explained in an email. The sensors can’t detect a person that is not moving. The challenge, Longtin continued, is in fooling the sensor into thinking something is there in motion to keep it active.

Wang described a situation in which a hotel had connected an occupant-detecting system to its HVAC system. When a person fell asleep in the room, however, the air conditioning turned off automatically. On a hot summer night, the person was frustrated. She put colored paper and a fan in front of the sensor, which kept the cool air from turning off.

Instead of using a fan and colored paper, the new system Wang is developing cuts the flow of heat to the sensor, which enhances its ability to recognize stationary or moving people.

Wang and her colleagues will use low-power liquid crystal technology with no moving parts. “The sensor detects you because you are a human with heat,” she said. “Even though you are not moving, the amount of heat is changing.”

The sensor will be different in various locations. People in Houston will have different temperature conditions than those in Wisconsin. Using a machine-learning algorithm, Wang said she can pre-train the system to respond to different people and different conditions.

She has developed a smart phone app so that the house can react to the different temperature preferences of a husband and wife. People can also choose night or day modes.

Wang also plans to work on a system that is akin to the way cars have different temperature zones, allowing one side of the car to be hotter than the other. She intends to develop a similar design for each room.

From left, Jon Longtin, Sotirios Mamalis and Benjamin Lawler. Photo courtesy of Stony Brook University

By Daniel Dunaief

It’s not exactly Coke and Pepsi designing a better soda. It’s not Nike and Reebok creating a more efficient sneaker. And, it’s not McDonald’s and Burger King uniting the crown and the golden arches. At Stony Brook University, it is, however, a combination of energy systems that haven’t historically worked together.

“Fuel cells and engines have been seen as competing technologies,” said Sotirios Mamalis, an assistant professor of mechanical engineering at SBU. “The truth of the matter is that these two technologies are very complementary because of their operating principals.”

Indeed, Mamalis is the principal investigator on a multi-year project to create a hybrid fuel cell-engine system that recently won a $2.3 million award from the Department of Energy’s Advanced Research Projects Agency-Energy.

Working with Benjamin Lawler and Jon Longtin at Stony Brook and Tom Butcher, leader of the Energy Conversion Group at Brookhaven National Laboratory, Mamalis plans to build a system that uses solid oxide fuel cells partnered with a split-cylinder, internal combustion engine. The engine system will use the tail gas from the fuel cell to provide additional power, turning the inefficiency of the fuel cell into a source of additional energy.

“These ARPA-E awards are extremely competitive,” said Longtin, adding “If you land one of these, especially a decent-sized one like this, it can move the needle in a lot of ways in a department and at the university level.” The group expects that this design could create a system that generates 70 percent fuel to electricity efficiency. That is well above the 34 percent nationwide average.

Reaching that level of energy efficiency would be a milestone, said Longtin, a Professor in the Department of Mechanical Engineering at Stony Brook. The core of the idea, he suggested, is to take the exhaust from fuel cells, which has residual energy, and run that through a highly tuned, efficient internal combustion engine to extract more power. The second part of the innovation is to repurpose the cylinders in the engine to become air compressors. The fuel cell efficiency increases with higher pressure.

A fuel cell is a “highly efficient device at taking fuel and reacting it to produce DC electricity,” Lawler said. One of its down sides, aside from cost, is that it can’t respond to immediate needs. An engine is the opposite and is generally good at handling what Lawler described as transient needs, in which the demand for energy spikes.

The idea itself is ambitious, the scientists suggested. “These projects are high-risk, high-reward,” said Mamalis. The risks come from the cost and the technical side of things.

The goal is to create a system that has a disruptive role in the power generation market. To succeed, Mamalis said, they need to bring something to market quickly. Their work involves engineering, analysis and design prior to building a system. The project could involve more tasks to reduce technical risk but “we’re skipping a couple of steps so we can demonstrate a prototype system sooner than usual,” Mamalis said.

They will start by modeling and simulating conditions, using mathematical tools they have developed over the years. Once they have modeling results, they will use those to guide specific experimental testing. They will take data from the engine simulation and will subject the engine to conditions to test it in a lab. 

“The biggest challenges will be in changing the operation of each of these two technologies to be perhaps less than optimal for each by itself and then to achieve an integrated system that ends up far better,” Butcher explained in an email. “The target fuel-to-electricity efficiency will break barriers and be far greater than is achieved by conventional power plants today.”

Butcher, whose role will be to provide support on system integration concepts and testing, suggested that this could be a part of distribution power generation, where power is produced locally in addition to central power plants. People have looked into hybrid fuel cell-gas turbine systems in the past and a few have been installed and operational, Mamalis explained. The problem is with the cost and reliability.

Mamalis and his colleagues decided they can tap into the inefficiency of fuel cells, which leaves energy behind that a conventional engine can use. The reason this works is that the fuel cell is just inefficient enough, at about 55 percent, to provide the raw materials that a conventional engine could use. A fuel cell that was more efficient, at 75 or 80 percent, would produce less unused fuel in its exhaust, limiting the ability of the system to generate more energy.

The team needs to hit a number of milestones along the way, which are associated with fuel cell development and engine and hybrid system development.

The first phase of the work, for which the team received $2.3 million, will take two years. After the group completes Phase I, it will submit an application to ARPA-E for phase II, which would be for an additional $5 million.

Lawler suggested that fundamental research made this kind of applied project with such commercial potential possible. “The people who did fundamental work and [were involved in] the incremental steps led us to this point,” he said. “Incremental work leads to ground-breaking ideas. You can’t predict when groundbreaking work will happen.”

The other researchers involved in this project credit Mamalis for taking the lead on an effort that requires considerable reporting and updating with the funding agency.

Every three months, Mamalis has to submit a detailed report. He also participates in person and on conference calls to provide an update. He expects to spend about 90 percent of his time on a project for which the team has high hopes.

“It’s an exciting time to be a part of this,” Longtin said. “These folks are pivotal and we have developed into a very capable team, and we have been setting our sights on larger, more significant opportunities.”

Gholson Lyon. Photo courtesy of Cold Spring Harbor Laboratory

By Daniel Dunaief

With the cost of determining the order of base pairs in the human genome decreasing, scientists are increasingly looking for ways to understand how mutations lead to specific characteristics. Gholson Lyon, an assistant professor at Cold Spring Harbor Laboratory, recently made such a discovery in a gene called NAA15.

People with mutations in this gene had intellectual disability, developmental delay, autism spectrum disorder, abnormal facial features and, in some cases, congenital cardiac anomalies.

In a recent interview, Lyon explained that he is trying to understand how certain mutations influence the expression of specific traits of interest, such as intelligence, motor development and heart development. He’s reached out to researchers scattered around the world to find evidence of people who had similar symptoms, to see if they shared specific genetic mutations in NAA15 and found 37 people from 32 families with this condition.

“I really scoured the planet and asked a lot of people about this,” said Lyon, who recently published his research in The American Journal of Human Genetics. The benefit of this kind of work, he explained, is that it can help screen for specific conditions for families at birth, giving them an ability to get an earlier diagnosis and, potentially, earlier treatment. “Being able to identify children at birth and to know that they are at risk of developing these disorders would, in a perfect world” allow doctors to dedicate resources to help people with this condition, he said.

Lyon published a similar study on a condition he named Ogden syndrome seven years ago, in which five boys in a single family died before they reached the age of 3. A mutation in a similar gene, called NAA10, led to these symptoms, which is linked to the X chromosome and was only found in boys.

Lyon found the genes responsible on NAA15 by comparing people with these symptoms to the average genome. The large database, which comes from ExAC and gnomAD, made it possible to do a “statistical calculation,” he said. The next steps in the research is to look for protein changes in the pathway in which these genes are involved. The people he studied in this paper are all heterozygous, which means they have one gene that has a mutation and the other that does not.

With this condition, they have something called haploinsufficiency. In these circumstances, they need both copies of the fully functioning gene to produce the necessary proteins. These mutations likely decrease the function of the protein. Lyon would like to study each of these cases more carefully to understand how much the mutation contributes to the various conditions. He looked for evidence of homozygous mutations but didn’t find any. “We don’t know if they don’t exist” because the defective gene may cause spontaneous miscarriages or if they just didn’t find them yet, he said.

Lyon plans on reaching out to geneticist Fowzan Alkuraya, who was trained in the United States and is working at King Faisal Specialist Hospital and Research Centre clinic in Saudi Arabia. The geneticist has studied the genes responsible for a higher rate of genetic disorders linked to the more common practice of people having children with cousins in what are called consanguineous marriages. 

Alkuraya works on the Saudi Human Genome Program, which studies the inherited diseases that have a higher incidence in Saudi Arabia.

For Lyon, finding the people who carry this mutation was challenging, in part because it hasn’t run in the family for multiple generations. Instead, Lyon and his colleagues, including Holly Stessman of Creighton University in Omaha, Nebraska and Linyan Meng at Baylor College of Medicine in Houston, Texas, found 32 unrelated families. In some of these families, one or two siblings carried this mutation in a single mutation.

By defining a new genetic disease, the scientists could help families seeking a diagnosis, encourage the start of early intervention such as speech therapy and connect patients with the same diagnosis. This can provide a support network in which people with this condition and their families know they are not battling this genetic challenge alone, Meng, the assistant laboratory director at Baylor Genetics and assistant professor at Baylor College of Medicine, explained in an email.

Every patient with an NAA15 mutation won’t have the same symptoms. “We see a range of phenotypes in these patients, even though they carry the same diagnosis with defects in the same disease,” Meng added. “Early intervention could potentially make a difference for NAA15 patients.”

Lyon works as a psychiatrist in Queens providing medication management. During his undergraduate years at Dartmouth College, in Hanover, New Hampshire, Lyon said he was interested in neurology and psychology. As he went through his residency at NYU, Columbia and New York State Psychiatric Institute, he gravitated toward understanding the genetic basis of autism, which he said is easier than conditions like schizophrenia because autism is more apparent in the first few years of life.

Lyon recently started working part time at the Institute for Basic Research in Developmental Disabilities on Staten Island. While Lyon appreciates the opportunity to work there, he is concerned about a potential loss of funding. “These services are vital” on a clinical and research level, he said. He is concerned that Gov. Andrew Cuomo (D) is thinking about decreasing the budget for this work. Reducing financial support for this institution could cause New York to lose its premiere status in working with people with developmental disabilities, he said.

“It has this amazing history, with an enormous number of interesting discoveries in Down syndrome, Alzheimer’s disease and Fragile X,” he said. “I don’t think it gets enough credit.”

As for his work with NAA, Lyon plans to continue to search for other people whose symptoms are linked to these genes. “I am looking for additional patients with mutations in NAA10 or NAA15,” he said.

Romeil Sandhu with his dog June. Photo courtesy of Romeil Sandhu

By Daniel Dunaief

Romeil Sandhu has had a busy year.

Last fall, the U.S. Air Force awarded him a $450,000 three-year grant, called the Young Investigator Research Program. At the beginning of this year, Sandhu won a $500,000 National Science Foundation Career Award.

The assistant professor in the Department of Biomedical Informatics at Stony Brook University is working in several directions on basic research that could help with everything from network security to autonomous cars.

The awards are a “tremendous accomplishment,” Allen Tannenbaum, a distinguished professor of computer science and applied mathematics/statistics at SBU, explained in an email. Sandhu won the career award on his “first try, which is very unusual. The Air Force award is a very high honor for a young researcher.”

Tannenbaum was Sandhu’s doctoral thesis adviser at Georgia Tech. Tannenbaum recruited Sandhu to join Stony Brook University and described Sandhu’s work as going in a “very promising direction.”

The Air Force funding is a new direction in which Sandhu is developing a theory around how to incorporate user input in three-dimensional autonomous systems that rely on two-dimensional imaging information.

An example of this, Sandhu explained, is where a soldier might make judgments maneuvering a vehicle around potentially deadly situations. His work involves translating three-dimensional interactive feedback controls based on two-dimensional imaging systems.

“When you take a video of a car, it’s in two dimensions,” he explained. The computer link between the collected images and the reality relies on geometric properties.

With most autonomous computer systems, a human is involved in the process, to prepare for what is called the “unknown unknown.” That is a term used to describe situations in which there is no way to predict all possible events.

Through his Air Force work, Sandhu ideally would like to seek greater autonomy for some of these self-directed systems. Removing human input entirely, however, generates a risk that may be too great. That is the case in cancer treatment as well as the systems used to protect soldiers. The work he is doing with the Air Force explores how to fuse human and computer-assisted decision making.

The NSF award, meanwhile, will use the confluence of geometry and control to explore vulnerability in time-varying networks. Sandhu is tackling problems in social systems, communication systems and cancer biology and biomedical informatics.

“We can devise this idea of a network, which is the same way with cancer and proteins,” he said. One protein sends a signal to another, causing a cascade of reactions that often promote cancer.

Sandhu is interested in how microfluctuations can pave the way to larger disruptions. In the social setting, such information may infect individuals or groups and such dynamics may allow it to influence macroscopic audiences.

“The prevailing idea is that there exist several changes that pave the way to a larger catastrophic failure,” he explained in an email. 

The grant is designed to exploit everything that can be modeled as a part of a network, to understand their vulnerability. Viral information and trending stories, Sandhu said, might have one dynamic, while conspiracy theories might have another. He would like to see how such information gains traction and spreads.

The way people interact occurs through multiple networks. Sandhu is studying how models can exploit real-world behavior. Geometry, he suggests, can begin to assist on more complex modeling problems that are time varying and multilayered.

When he describes how he studies systems such as cancer, he likens the process to a waterbed. A drug or therapy may knock out a specific gene, which could limit cancer’s growth. When that gene changes, however, it creates a wave along the bed, enabling another potential genetic process to occur. While it has a more precise definition in control, it is akin to sitting on a waterbed in suppressing one sequence only to give rise to another.

Sandhu, who arrived at Stony Brook University in 2016, grew up in Huntsville, Alabama, and then spent over a decade going to school in Georgia, where he earned his doctorate at Georgia Tech.

In some ways, Sandhu’s Huntsville background, which includes lettering in high school soccer for four years as a center midfielder, is similar to one of the challenges in perception he studies through his work. 

“Think of me as one person in a network,” he said. “In a lot of the research we look at, we want to know how microfluctuations such as myself give way to a larger perception.”

Sandhu explained that the general perception of Huntsville and Alabama is different from his experience.

Most people are surprised that Huntsville has the second largest research park in the nation, at Cummings Research Park. Huntsville also has numerous aerospace companies.

The city generally ranks highly as one of the more educated in the country, he said. This is due in large part to the tech community that supports the government. The town is largely influenced by NASA and the surrounding military aerospace community, which Sandhu believes impacted his worldview, career path and research initiatives.

Indeed, one of the goals Sandhu has for his NSF grant is to help educate the high school students of people serving in the military. He said he appreciated the military families who were such an integral part of his upbringing.

Sandhu has two doctoral students and two master’s students in his lab. He also plans to participate in the Simons Summer Research Program at SBU where he will add a high school student. He is excited about the next phase of his research.

“The best part is the challenges that lie ahead,” he explained in an email. “Whether it is targeted therapy and cancer research, social computing and/or interactive computing, we are just beginning to understand very complex issues. Our hope is that we can make a contribution.”

Eli Stavitski. Photo by Alena Stavitski

By Daniel Dunaief

Humans learned to fly by studying birds and have learned to edit genes by understanding the molecular battle between bacteria and viruses. Now, we may also learn to take carbon dioxide, a necessary ingredient in photosynthesis, and use it to produce energy.

Eli Stavitski, a physicist at Brookhaven National Laboratory, is working with a new form of electrocatalyst to convert carbon dioxide into carbon monoxide, which can become part of an energy process.

Researchers have used noble metal electrocatalysts, such as gold and platinum, to promote this reaction. The problem with this method, however, is that these metals are rare and expensive.

In most of the reactions with other potential electrocatalysts, however, a competing reaction, called water splitting, reduces the amount of carbon monoxide produced.

Single atoms of nickel, however, woven into a lattice of graphene, which is a monolayer of carbon, produces a much higher amount of carbon monoxide, while minimizing the unwanted water splitting side reaction.

Indeed, these single atoms of nickel converted carbon dioxide to carbon monoxide with a maximum selectivity of 97 percent.

“The critical aspect of the work is that they show a change in chemical selectivity” resulting in the production of the desired products, Dario Stacchiola, a group leader in interface science and catalysis at the Center for Functional Nanomaterials at BNL, explained in an email. An important part of this study is the “ability to detect single atoms (atomic needles in a carbon-based graphene haystack) which is possible in [Stavitski’s] instrument.”

Stacchiola and Stavitski are collaborating on projects related to heterogeneous catalysis. They synthesize and test materials and then measure them in a state-of-the-art beamline. Carbon monoxide can be used to produce useful chemicals such as hydrogen, which can power fuel cell vehicles. The process can contribute to something called carbon sequestration, in which carbon dioxide is removed from the atmosphere.

While carbon monoxide is a deadly gas when it’s breathed in, Stavitski said manufacturing facilities deal with toxic substances regularly and have policies and procedures in place to minimize, monitor and contain any potential dangers. On the scale of toxicity, carbon monoxide isn’t the worst thing by far, he explained.

Indeed, in refining crude oil to fuels and chemicals, refining companies regularly produce highly toxic intermediates that they control during the manufacturing process.

The way researchers create the nickel catalysts is by taking a sheet of graphene and creating defects in it that they then fill with nickel. The defects define whether the atoms are in plane or stick out, which determines the rate of reaction.

Getting the defects at just the right size requires balancing between making them small enough so that it doesn’t disrupt the graphene, but large enough to accommodate the metal atoms.“There is an opportunity to lower the costs by designing conventional supports for single atom nickel,” Stavitski said.

At $6 a pound, nickel is considerably cheaper than platinum, which cost $150 a pound. Still, it is among the more expensive base metals.

“The single atom field is exploding,” he said. “Everyone is trying to develop this unique combination of support and metal that allows for the stabilization of single atoms. It’s very likely that we’re paving the way to a much larger adoption of this material in industry.”

Stavitski suggested that the field of electrocatalysts using nanomaterials has the potential to revolutionize industrial and commercial processes. The work he and his colleagues did with nickel, while compelling in its own right, is more of an evolutionary step, benefiting from some of the work that came before and finding a specific application that may become a part of a process that converts carbon dioxide into the energy-efficient carbon monoxide, while minimizing the production of an unwanted competing reaction.

The next set of experiments is to verify the same concept of graphene as a support for single atom catalyst, which can lead to a whole family of active and selective materials. Stavitski plans to explore combinations of metals, where he could link one metal to another to fine tune its electronic properties to develop metals that can target a wide spectrum of chemical reactions.

The work Stavitski is conducting with electrocatalysts is one of several areas he is exploring in his lab. He is also looking at developing types of batteries that are not based on lithium. 

With increased demand, primarily from electric vehicle manufacturing, lithium prices have “skyrocketed,” he explained in an email. “It’s important to develop batteries that employ sodium, which is cheap and abundant. Technologically, sodium batteries are much more difficult to deal with.”

Stavitski collaborates with a group at BNL led by Xiao-Qing Yang, who is the group leader for electrochemical energy storage.

Stacchiola has known Stavitski since 2010. He described him as “active and innovative” and suggested that this new capability of detecting single atoms in complex materials is “critical and is giving [Stavitski] significant growing exposure in the scientific community.”

Stacchiola appreciates how his colleague gets “fully immersed in every project he associates with.”

Stavitski grew up in the Soviet Union. After college, he moved to Israel and then the Netherlands. He arrived at BNL in 2010.

Currently a resident of South Setauket, Stavitski is married to Alena Stavitski, who works at BNL in the quality management office. The BNL couple have two sons who are 3 and 6 years old.

Stavitski, who speaks Russian, Hebrew and English, enjoys traveling.

As for his work, he is excited by the possibility of using the expanding field of nanomaterials to enhance the efficiency of commercial and energy-related processes.

Annie Laurie W. Shroyer and Thomas Bilfinger

By Daniel Dunaief

Convenience can come at a cost, even in medicine. When it comes to a heart procedure called cardiac artery bypass surgery, that cost could make a difference in the outcome for the patient.

Annie Laurie W. Shroyer, vice chair for research and professor in the Department of Surgery at Stony Brook University School of Medicine, and Thomas Bilfinger, a professor of surgery in the Division of Cardiothoracic Surgery at SBU, found that the mortality and major morbidity rates were lower for patients of surgeons performing procedures at a single center compared to those performing procedures at more than one center. 

Among physicians who operated at two or more hospitals, these surgeons performed better at their home hospital than at a secondary center.

They’ve published their findings in the Annals of Thoracic Surgery. The Society of Thoracic Surgeons identified the article as the Continuing Medical Education article for the month. The article will provide a much more in-depth learning experience to a subgroup of the journal’s subscribers who seek Continuing Medical Education credits. This, Shroyer explained, will make it more likely that cardiac surgeons will read it thoroughly and discuss it.

“We believe that, based on the results, particularly complex coronary artery bypass grafting (CABG) procedures may have a better outcome at bigger institutions,” Bilfinger explained in an email. Mortality for these procedures overall in the United States is low and the analysis is about differences of a few tenths of a percent, which becomes statistically significant due to the low number.

The central issue, Bilfinger said, is whether “the mother ship does better or worse than the satellite. Decision making about centralizing versus a de-centralized approach seems to be less driven by outcomes and rather by business decisions in many circumstances. The study adds some subjective data to this discussion.”

Using a measure called observed-to-expected mortality ratios based on the health of the patient and risks of the procedure, the ratio for multicenter surgeons was higher for the satellite facilities compared to their home facilities. The ratios were 1.17 for surgeons operating at satellite facilities versus 1.01 for multicenter surgeons performing the procedure at their home hospital.

The volume of surgeries is a complicated issue, Bilfinger cautioned. “There are very well-performing smaller volume places throughout the country,” he explained in an email. “It involves dedication to the procedures from admission to discharge.”

Assuming the surgeon is just as effective in different hospitals, which is “open to discussion,” any observed difference could be attributable to the system, Bilfinger explained. Measuring the effectiveness of the participants in the process, including nurses, anesthesiologists and orderlies, is a question for ongoing research, he continued.

Joseph Carey, a cardiovascular and thoracic surgeon in Torrance, California, conducted a study based on information from California about a decade ago. In an email, Carey suggested that “you pay a price in quality working in unfamiliar conditions and I believe hospital managers do not want their surgeons traveling about.” He added that this paper “is an important reminder” of this.

Carey added that hospital systems and the makeup of the “heart team” may also be important to the outcome of a surgery.

Future research, which Shroyer plans to conduct, will evaluate other factors, such as patient risk, processes and structures of care, that impact cardiac surgical outcomes.

Other researchers could extend this study, which compares the quality of care for surgeons who work at single sites and multisites, to other areas of medical care, enabling hospital networks, insurance companies and patients to make informed risk-based decisions prior to approving difficult procedures.

The challenge, however, with similar studies for other conditions, is in finding national information. “This is the best documented group of procedures there is in the country,” Bilfinger said. For a procedure like back surgery, it might be difficult to come up with a comparable study, although Bilfinger said he “suspects strongly that this is a very similar relationship.”

Shroyer and Bilfinger will extend their work to another cardiothoracic operation. They have submitted a proposal to the Society of Thoracic Surgeons to start a parallel project to look at the difference in risk-adjusted outcomes for mitral valve procedures that compare single-center versus multicenter surgeons. The diversity of procedures may need to be considered in comparing single and multicenter surgeons.

Bilfinger said he recognizes that some doctors and hospital networks may find these conclusions disconcerting. It may give them pause in the internal discussion about value added by new satellites in any system, he explained. “This is worth a public debate. This is one of these aspects of modern health care that the consumer is not aware of.” The average consumer may not put too much emphasis on this, although the sophisticated consumer on Long Island may change or make decisions based on this type of information, he said.

Shroyer and Bilfinger, who have worked on the same floor at the Health Sciences Center since Shroyer arrived from Colorado in 2007, decided to collaborate on this project after a discussion during lunch. The duo were eating at SBU’s Simons Center Café when they were discussing the differences in outcomes for single and multicenter surgical procedures. They submitted a request to access the National Adult Cardiac Surgery Database in 2014 to the Society of Thoracic Surgeons.

For patients who are going to have a cardiac surgical procedure, Shroyer recommends that people choose their surgeon and surgery center “wisely.” She recommends researching the surgeons and their corresponding center’s bypass specific outcomes. She highlights two publicly available resources, which are Adult Cardiac Surgery Database Public Reporting|STS Public Reporting Online and Doctor Ratings — Consumer Reports.

Shroyer cautions that these ratings are somewhat outdated, so she suggests patients ask their surgeons directly about their more recent outcomes. She would also recommend contacting patients.

After conducting this study, Shroyer believes it would likely help patients if they searched for doctors who only perform bypass procedures at a single hospital. She also believes it is important for patients to consider surgeon-specific and center-specific risk-adjusted outcomes.

Ultimately, she said, the decision about a surgeon and a site for surgery is an important one that patients should make based on the likelihood of the best outcome.

“Patients should research their cardiac surgeon-hospital decision even more carefully than if they were buying a new home or a new car,” she explained in an email. “Their future health lies in their cardiac surgeon’s hands.”