Science & Technology

SBU team member Steve Forrest scales the rock face as chinstrap penguins look on. Photo by Christian Åslund

By Daniel Dunaief

The canary in the Arctic coal mines, chinstrap penguins need more ice. These multitudinous flightless birds also depend on the survival and abundance of the krill that feed on the plankton that live under the ice.

With global warming causing the volume of ice in the Antarctic to decline precipitously, the krill that form the majority of the diet of the chinstrap penguin have either declined or shifted their distribution further south, which has put pressure on the chinstrap penguins.

Indeed, at the end of December, a team of three graduate students (PhD students in Ecology and Evolution Alex Borowicz and Michael Wethington and MS student in Marine Science Noah Strycker) from the lab of Heather Lynch, who recently was promoted to the inaugural IACS Endowed Chair of Ecology & Evolution at Stony Brook University, joined Greenpeace on a five week mission to the Antarctic to catalog, for the first time in about 50 years, the reduction in the number of this specific penguin species.

The team boarded Greenpeace’s ship, the Esperanza, for a five week mission. Photo by Christian Åslund

The group, which included  private contractor Steve Forrest and two graduate students from Northeastern University, “saw a shocking 55 percent decline in the chinstrap on Elephant Island,” Lynch said. That drop is “commensurate with declines elsewhere on the peninsula.”

Elephant Island and Low Island were the targets for this expedition. The scientific team surveyed about 99 percent of Elephant Island, which was last visited by the Joint Services Expedition in 1970-1971.

The decline on Elephant Island is surprising given that the conditions in the area are close to the ideal conditions for chinstraps.

In some colonies in the Antarctic, the declines were as much as 80 percent to 90 percent, with several small chinstrap colonies disappearing entirely.

“We had hoped that Elephant Island would be spared,” Lynch said. “In fact, that’s not at all the case.”

While many indications suggest that global warming is affecting krill, the amount of fishing in the area could also have some impact. It’s difficult to determine how much fishing contributes to this reduction, Lynch said, because the scientists don’t have enough information to understand the magnitude of that contribution.

The chinstrap is a picky eater. The only place the bird breeds is the Antarctic peninsula, Elephant Island and places associated with the peninsula. The concern is that it has few alternatives if krill declines or shifts further south.

“Chinstraps have been under-studied in the last few decades, in part because so much attention has been focused on the other species and in part because they nest in such remote and challenging places,” Lynch explained in an email. “I hope our findings raise awareness of the chinstraps as being in serious trouble, and that will encourage everyone to help keep an eye on them.”

While these declines over 50 years is enormous, they don’t immediately put the flightless waterfowl that tends to mate with the same partner each year on the list of endangered species because millions of the sea birds that feel warm and soft to the touch are still waddling around the Antarctic.

Researchers believe that the biggest declines may have occurred in the 1980s and early 1990s, in part because areas with more regular monitoring showed reductions during those times.

Still, where there are more recent counts to use as a standard of comparison, the declines “show no signs of abating,” Lynch explained.

The evidence of warming in the Antarctic has been abundant this year. On Valentine’s Day, the Antarctic had its hottest day on record, reaching 69.35 degrees Fahrenheit. The high in Stony Brook that day was a much cooler 56 degrees.

“What’s more concerning is the long term trends in air temperature, which have been inching up steadily on the Antarctic Peninsula since at the least the 1940’s,” Lynch wrote in an email.

At the same time, other penguin species may be preparing to expand their range. King penguins started moving into the area several years ago, which represents a major range expansion. “It’s almost inevitable that they will eventually be able to raise chicks in this region,” Lynch suggested.

The northern part of the Antarctic is becoming much more like the sub Antarctic, which encourages other species to extend their range.

Among many other environmental and conservation organizations, Greenpeace is calling on the United Nation to protect 30 percent of the world’s oceans by 2030. The Antarctic was the last stop on a pole to pole cruise to raise awareness, Lynch said.

One of the many advantages of traveling with Greenpeace was that the ship was prepared to remove trash.

“We pulled up containers labeled poison,” Lynch said. Debris of all kinds had washed up on the hard-to-reach islands.

“People are not polluting the ocean in Antarctica, but pollution finds its way down there on a regular basis,” she added. “If people knew more about [the garbage and pollution that goes in the ocean], they’d be horrified. It is spoiling otherwise pristine places.”

Lynch appreciated that Greenpeace provided the opportunity to conduct scientific research without steering the results in any way or affecting her interpretation of the data.

“We were able to do our science unimpeded,” she said.

Counting penguins on the rocky islands required a combination of counting birds and nests in the more accessible areas and deploying drones in the areas that were harder to reach. One of Lynch’s partners Hanumant Singh, a Professor Mechanical and Industrial Engineering at Northeastern University, flew the drones over distant chinstrap colonies. The researchers launched the drones from land and from the small zodiac boats.

The next step in this research is to figure out where the penguins are going when they are not in the colony. “Using satellite tags to track penguins at sea is something I’d like to get into over the next few years, as it will answer some big questions for us about where penguins, including chinstraps, are trying to find food,” Lynch said.

Above, from left, Kenneth Kaushansky, Dean of the Renaissance School of Medicine; Anissa Abi-Dargham; Henry Tannous; Ute Moll; and Michael Bernstein, Interim President of SBU.

By Daniel Dunaief

A heart and lung doctor, a researcher who works on imaging for schizophrenia and a scientist working with a mutation that affects cancer last month received endowed inaugural chair positions at Stony Brook University.

Ute Moll is the Renaissance Endowed Professor in Cancer Biology, Anissa Abi-Dargham is the Lourie Endowed Chair in Psychiatry and Henry Tannous is the General Ting Feng Cheng Endowed Chair in Cardiothoracic Surgery.

In addition to adding the prestigious titles and winning support from local benefactors and philanthropists, the three researchers will each receive annual financial support from their positions that will sustain their research and education efforts. TBR News Media is highlighting the research from each of these standout scientists.

Ute Moll

Ute Moll

A native of Germany, Ute Moll, who is studying the six most common mutated forms of the highly researched p53 gene, is grateful for the donors, the funds and the recognition. “It’s pretty prestigious to have an endowed chair or professorship attached to your name or title,” she said 

Moll described the p53 mutations as the “most common mutation in cancer.” She has been working with a mouse model. The p53 R248 hotspot is the single most common variant in all p53 altered tumor types, which occurs in about 66,000 newly diagnosed cancer patients in the United States each year.

If these mice also have a gene called Myc, they get either liver or colon cancer. By receiving an estrogen derivative drug called Tamoxifen, which is used in breast cancer, the active, mutated version of the p53 gene is turned off when another gene called Cre recombinase is activated. By removing the p53 gene, the mice live two to three times longer than they would have.

In a typical mouse, cancer can cause over 100 tumor nodules, leaving almost no normal liver. When Moll and her colleagues turned off the mutant gene, the size of the cancer is much more limited, with only a few remaining nodules.

One particular mouse lived for more than two months, eventually dying of an unrelated lymphoma. The liver, however, which had an infection across the entire organ, didn’t show a single trace of a tumor. It was completely normal, despite the ubiquitous tumor nodules before treatment.

Thus far, targeting this mutated p53 is a concept Moll and her colleagues have developed in pre-clinical mouse models of lymphoma, colon and liver cancer, but it doesn’t yet have a clinical application. 

Liver cancer used to be relatively rare in the population, driven largely by infection from hepatitis B and hepatitis C, as well as through alcoholism. Amid an epidemic of obesity, people are developing a chronically inflammatory liver condition, which increases the incidence of liver cancer.

Anissa Abi-Dargham

Anissa Abi-Dargham

A specialist in Positron Emission Tomography (or PET) imaging for schizophrenia, Anissa Abi-Dargham is pleased with the opportunity to deploy the funds for her work at her discretion.

“The beauty of these funds is that they are totally flexible,” she explained, adding that she plans to use the funds to pursue new research ideas that might not otherwise get funding until she can use data to prove a concept or principal. 

“This is really a great honor because it means that the institution believes in you and wants to invest and retain you,” she said.

In her work, Abi-Dargham has been using imaging to see what is causing dopamine dis-regulation, either with too much or too little of the neurotransmitter. 

She is looking at two systems that may explain the imbalance: the cholinergic system and the kappa opioid system.

Abi-Dargham had been at Columbia University for 20 years before joining Stony Brook over three years ago. She appreciates the school investing in a state-of-the-art imaging center. “The people in charge of this imaging center are very much investing in promoting imaging for neuroscience and psychiatry,” she said.

Based on her findings in schizophrenia, other investigators in the United Kingdom have documented dopamine levels before schizophrenia symptoms begin.

She hopes her research discovers biomarkers that can be used to predict who is going to convert to having schizophrenia.

Patients do better when the onset of symptoms is later in their lives because their more mature brain has fostered better organized life, skill sets, and relationships.

She is also testing whether other markers, such as a neuromelanin, which is a metabolite of dopamine and binds iron-like materials, will show up on a Magnetic Resonance Imaging scan before the disease.

Henry Tannous

Henry Tannous

Henry Tannous joined Stony Brook University in 2016 and is excited to be a part of the current team and to help shape the future of clinical practice and research.

Tannous called the endowed chair position an “absolute honor.” It will not only allow him to continue with his current work, but it’s also going to enable him to expand his research. He will also use some of the funds to provide continuing education for his staff.

The financial support will allow him to hire research assistants and access national databases. Tannous and his research team of cardiothoracic and lung scientists use registries from the New York State Department of Health registry and the Society of Thoracic Surgeons, each of which provides the data for a price.

With his lung work, Tannous focuses on state 1 lung cancer. Traditionally, he said, people have received a diagnosis late in the development of the disease. Over the past few years, doctors have diagnosed patients at an earlier point.

Earlier diagnoses became more prevalent after Medicare approved lung cancer screening in 2015, which picked up more cases while patients were still in the earlier stages, when the cancer might otherwise be asymptomatic.

“We would like to know more about how the disease affects [patients] and their quality of life,” Tannous said. His lab has a collaboration with Mount Sinai Hospital to learn more about the effect of the disease on the lives of the patients.

With his heart research, he’s focusing on aortic disease and is testing the limits of the Trans Catheter Aortic Valve Replacement.

Photos courtesy of SBU

By Daniel Dunaief

Two researchers from Brookhaven National Laboratory were stuck on a ship trapped in ice near the North Pole — and they couldn’t have been happier.

In fact, one of them, Matt Boyer, an Atmospheric Scientist at BNL, is returning to the German ship Polarstern for six of the next seven months. The Polarstern is part of a 20-nation effort that will gather information about the Arctic to understand climate change. The scientific collaboration, called MOSAiC (Multidisciplinary Drifting Observatory for the Study of Arctic Climate), started in September and will involve collecting data for a full year.

The scientists are measuring aerosols, cloud particles, and other data through conditions that are among the most challenging on the planet. Researchers aboard the Polarstern regularly endure cold temperatures, fierce winds, minimal to no sunlight and the threat of polar bears unafraid of humans.

Janek Uin, an Associate Atmospheric Scientist at BNL, is working with instruments that measure properties of atmospheric aerosol particles such as their size, the concentration of particles per unit volume of air, how the particles are affected by water vapor and how much light the particles scatter, which affects the sunlight that reaches the Earth’s surface.

Arthur Sedlacek, an atmospheric chemist with the Environmental & Climate Sciences Department at BNL, is one of a host of scientists collecting data from the Polarstern. Indeed, Sedlacek traveled to Tromsø Norway when the ship departed, where he prepared to measure the accumulation of black carbon in the Arctic. 

Caused by burning fossil fuels, emissions from distant wildfires, among other things, black carbon can cause polar ice to melt. When there is sun, the black carbon prevents the reflection of the light, which further darkens the white surface, either through exposure of the underlying ground or previously deposited black carbon.

Sedlacek, who did not travel aboard the Polarstern, said scientists around the world are “itching to see the data” from this ambitious mission. The data collection is “so unique and so important that it will not only help us better understand the current (pristine) state of the cryosphere, but it will also [allow scientists] to better understand (and quantify) how the Arctic is responding to climate change.”

Uin, who is an instrument mentor for about 30 instruments worldwide, recalled how he went out for a fire drill. Following his designated path and waiting for the signal to return, Uin decided to snap some pictures of a frozen and uneven landscape that appeared blue during much of the day, when the faint rays of the sun barely made it over the horizon. Unable to maneuver the camera to his satisfaction, Uin took off his gloves. His exposed fingers became numb in the wind. After he put his gloves back on, it took about 10 minutes for the feeling to return to his hands.

Boyer, meanwhile, who spent more of his time working outside than Uin, helped set up the meteorological site about 1 kilometer away from the ship and is monitoring the size and concentration of organic and inorganic aerosol particles.

The size and concentration of the particles determines how they behave in atmospheric processes, Boyer explained. The size of the particle influences its light scattering ability, how long it stays in the atmosphere, the human health impact and its ability to form clouds, among other properties.

The process of working near the North Pole requires a high level of patience. A task that might take two hours in a lab, for example, might require as long as four days to complete in Arctic conditions.

Boyer described how the moisture from his own breath sometimes froze in his face. “I prefer not to wear goggles” because they fog up, he explained. When he exhaled, the water vapor in his breath caused his eyelids to freeze shut. “You have to constantly close your eyes and pull the ice off your eyelids.”

Boyer had to hold onto a piece of metal when it was well below 0 degrees Fahrenheit and windy. Placing the bolts, nuts and screws into a hole with a glove on is “almost impossible,” Boyer said, although once those items are in place, holding a wrench with gloves on is manageable

Each time people work outside, polar bear guards constantly watch the horizon to make sure the carnivorous creatures don’t approach scientists. While the ship is not a cruise vessel, it offers pleasant amenities, including a small pool, a sauna, an exercise room and nourishment Uin and Boyer, who were roommates aboard the Polarstern, appreciated.

“The food was excellent,” Uin said. “Working long hours in extreme conditions in close quarters, the food has to be good. If it’s bad, morale plummets.” The scientist has been on three ice breakers and the food has always been high quality. 

Uin appreciated the opportunity to take the journey and to conduct the scientific research. “I am reminded how lucky I am that people trust me to do this,” he said.

Uin enjoys the opportunity to look at the ice, which appears blue because of the low light. “People think it’s all white,” he said. “There’s a constant twilight and an all-encompassing blue.” He is excited to look at the information the instruments collect and is “certain that the data will help to bring new insights into the very complex processes governing Earth’s climate and help better predict future trends.”

Boyer, who plans to leave BNL this month to pursue his PhD at the University of Helsinki, said he appreciated the opportunity to be a part of a multi-national team. “I’m one of the luckier people on the planet,” Boyer said. “Not many people will see the Arctic and the Antarctic and I’ve seen both,” adding that there is a satisfaction at being involved with something that is “much larger than myself. I’m a part of a community that works together towards a common goal. It’s nice to be a part of an international team working with people from places and countries who put aside their differences.”

All photos from Janek Uin

Maureen O’Leary. Photo courtesy of SBU

By Daniel Dunaief

Like the great white shark that needs to keep swimming to stay alive, scientific databases that provide resources to researchers from all over the world can’t stay still or they risk losing their usefulness and reliability.

The directors of these resources need to find funds that will ensure that the data remains accessible and that users, who range from high school students conducting work for a class to the chairman of research departments at colleges, can benefit from the availability of information.

Maureen O’Leary. Photo from SBU

Maureen O’Leary, a Professor and Graduate Program Director at the Department of Anatomical Sciences at the Renaissance School of Medicine at Stony Brook University, is looking to ensure that Morphobank, a web application and database that allows scientists around the world to share raw data on the structure of various organisms to help determine their evolutionary links, receives funds that sustain its mission.

O’Leary helped start MorphoBank in 2000 to encourage researchers to share data and propel science forward and is currently the director. By making observations of the structures of organisms available in one place online, she hoped to help advance the field of phylogenetics — the relationships among organisms in a family tree — while cutting down on the need to reproduce data from the same fossils at museums or other sites.

Up to this point, O’Leary has found financial support for the effort through grants from the National Science Foundation, the American Museum of Natural History and the National Oceanographic and Atmospheric Administration.

Looking to the future, however, O’Leary wanted to create a financial plan that would ensure ongoing funding for a database that has not only helped researchers explore data, but has also enabled collaborators to share information privately in a non-public area of MorphoBank.

O’Leary has been working with Phoenix Bioinformatics, a nonprofit group based in Fremont, California that has developed funding models for databases. Phoenix started its operations in 2013 after the staff of TAIR, a curated database for plant genome information, lost its grant funding.

The business is in the early stages of helping O’Leary with Morphobank, said Eva Huala, the Executive Director of Phoenix and a founding member of TAIR.

Phoenix has helped construct a financial model that is similar to the way university libraries and scientists pay for subscriptions to journals. The prices vary depending on the database the library subscribes to and the amount of usage of that database from the university. 

Huala said Phoenix is providing software that helps recruit members. The company is also enabling users to see whether their institution is supporting MorphoBank. So far, the Executive Director is “encouraged by the response. We know that this often takes several months or longer for libraries to decide” to lend financial support, she said.

The cost of running MorphoBank is connected to the time people spend curating as well as fixing bugs or managing computer-related challenges. Without software patches and fixes, the databases can run into problems.

Universities often require their researchers to make sure the data they collect is available to the scientific community, Huala explained, adding that MorphoBank can give scientists a way to “demonstrate the impact of their research” by offering download and viewing statistics for their data.

Mike D’Emic, an Assistant Professor in Biology at Adelphi University and a member of the Executive Committee of MorphoBank, has used the database for over seven years.

D’Emic suggested that MorphoBank “saves people from reinventing the wheel in doing science” by providing free, raw data. Scientists don’t have to travel to museums or other sites to gather the same information.

An early career researcher or student might have a small grant to visit three or four museums. These scientists can “supplement that data set with information from MorphoBank that’s multiple times the value of a grant they would have gotten,” D’Emic noted.

Scientists can freely use data from MorphoBank that would have taken tens of thousands of dollars to acquire. This includes photographs of a dinosaur skull from distant countries or CT scans that can be expensive to produce.

D’Emic, who helped convince the Adelphi library to provide financial support for the database, said MorphoBank addresses bug reports quickly, fixing problems with a few days.

Prior to O’Leary’s effort to start MorphoBank, a researcher might need to search through the appendices or the published reports from other scientists in their field to access raw data for tree building, sometimes retyping by hand large spreadsheets of numerical scores.

MorphoBank has been “invaluable and transformative in terms of the way people access and replicate science,” D’Emic said.

Some journals have started urging authors to publish their data online. The Journal of Vertebrate Paleontology strongly recommends uploading dataset, character descriptions and images to an online repository.

“For not too much money, MorphoBank has a huge impact on science,” D’Emic said, who said it was a cost effective boost to evolutionary biology and related fields

Scientists have changed significantly in their approach to sharing information. Around 30 years ago, some researchers wouldn’t always share their raw data. Other scientists would then have to spend thousands of dollars to travel to places like Thailand, Australian and Madagascar.

“People have come around” and are more comfortable exchanging data, sometimes as they produce it, D’Emic said. “MorphoBank has been an integral venue for convincing people you should share.”

O’Leary believes researchers have evolved in the way they think about the information they collect as a part of their studies.“We have reached a social transition where scientists get used to not only writing a paper and walking away, but making sure the data content is in a digitally reusable format,” she said.

O’Leary feels fortunate to have received funding for over two decades for MorphoBank. She plans to remain the director when MorphoBank moves to Phoenix. It’s an “important and dynamic tool” and she feels a “responsibility to allow its continuity.”

 

Members of the team at Brookhaven Lab’s Accelerator Test Facility from left, Mark Palmer, Dejan Trbojevic, Stephen Brooks, George Mahler, Steven Trabocchi, Thomas Roser, and Mikhail Fedurin. Photo from BNL

By Daniel Dunaief

Scientists at Brookhaven National Laboratory and Cornell University have tested and developed a new “green” accelerator. Capturing and reusing the energy from electrons that are decelerating, the newly designed model, called CBETA, will have uses in everything from computer chip manufacture to medicine to missile defense to basic science.

Employing permanent magnets, which require no energy to operate, and superconducting material, these researchers brought to fruition an idea first formulated in 1965 by Maury Tigner, professor emeritus at Cornell University.

“It was talked about for many years,” said Thomas Roser, who just completed his 10th year as chairman of the Collider-Accelerator Department at Brookhaven National Laboratory. “To put everything together in an energy efficient way could have a significant impact for the future.”

Indeed, the new design could lower the energy needs of a future facility like the Electron Ion Collider, which BNL plans to complete in 2030.

“We all have a responsibility to contribute to the well-being” of the planet, including in efforts to reduce the energy consumption of devices used to unlock the mysteries of the universe and produce future technology, said Roser.

Schematic of the Cornell-BNL
ERL Test Accelerator.
Image courtesy of Cornell University

One of the many advantages of the new accelerator design, which was tested in the early morning hours of Dec. 24 at Cornell, is that it captures and reuses the energy in a multi-turn particle accelerator. The idea of the accelerator was to enable beams of different energy to travel through the same magnets on slightly different paths in an oblong structure. 

The design is akin to a relay race on a running track. Each lane has runners that move at their own speeds. When it is time for one of the runners to slow down and leave the track, she shares the energy from her sprint with an intermediary, which drives the next runner forward at a rapid pace, while she decelerates in a nearby loop.

In the case of the accelerator, the intermediary is a superconducting radio frequency cavity.

A key design feature is that multiple beams recirculate in these cavities four times. This cuts down on future construction costs and reduces the size of an accelerator from about a football field to a single experimental hall, according to information from Cornell.

A fresh electron beam allows researchers to get a better quality beam than in the traditional way of operating an accelerator, in a ring that would circulate continuously. 

“The beam is always refreshed, and what gets recirculated is the energy,” Roser said.

The high quality, bright beam creates bright lasers that companies may be able to use to manufacture new chips for computer or phone technology. These accelerators could also make infrared lasers that could melt objects. This type of application could help with defense department efforts to thwart an incoming missile. While BNL is taking steps to work on applications in other areas, the Department of Energy laboratory is not involved in such missile defense applications.

In the medical arena, this kind of accelerator could enable the construction of smaller, simpler and lighter devices for proton therapy to treat cancer. The multi-energy beam transport of CBETA would allow the building of more compact and less expensive gantries that deliver beams to the patient.

Using different energies at the same time, doctors could “treat cancers at different depths inside the body,” Roser said. “That’s an application for this unique transport.” Proton therapy could become cheaper and available in more hospitals with this approach, he asserted.

For Dejan Trbojevic, the principal investigator on the CBETA project and a senior physicist from BNL, the successful test of the concept was a validation of over 20 years of work.

“You can do a lot of simulations assuming realistic errors,” but the actual experiment demonstrating the concept “makes a big difference,” he explained in an email.

The BNL scientist was at Cornell in late December, where he and his colleagues celebrated the results with champagne.

Trbojevic, who had developed the concept of using a single beamline instead of multiple beamlines, hopes to use the new design to create a less expensive design to proton therapy treatment for cancer

“I’m trying to make this cheaper so more hospitals can have it,” Trbojevic said. He has already made contact with companies and a professor in Europe who hopes to use the design concept. He has also requested funding from the Department of Energy.

Beyond the excitement of the recent collaboration with Cornell on the new accelerator design, Roser reflected on his first decade as chairman of the Collider-Accelerator Department.

The BNL department is leading the world in many accelerator technologies and is collaborating closely with CERN, which was founded in Europe seven years after BNL.

Indeed, this year marks numerous celebrations for the department. The Relativistic Heavy Ion Collider, or RHIC, has been operating for 20 years and will become a part of the new Electron Ion Collider. At the same time, the Alternating Gradient Synchrotron, where research for three Nobel Prizes was conducted, marks its 60th year of generating scientific results.

And, to top off the historical trifecta, Ernest Courant, a former BNL Scientist who teamed up with Stanley Livingston and Hartland Snyder to create the strong focusing principle, turns 100 in March. Courant, who worked with Trbojevic on a paper describing the single beamline concept in 1999, helped provide a critical step for modern particle accelerators.

As it did 10 years ago, the department is rolling these three celebrations into one in June.

Courant can’t attend the event because he lives in a retirement home in Ann Arbor, Michigan near his son. BNL will likely show photos and video from Ernest’s birthday at the celebration.

As for the recently completed collaboration with Cornell, Roser believes the work is an important step.

“It’s a new concept and a new type” of accelerator, Roser said. “That doesn’t come around very often. There are cyclotrons and there are linear accelerators. This is a combination of a circular and linear accelerator put together in a new way.”

 

Lingbo Zhang Photo from CSHL

By Daniel Dunaief

In the span of a few months, Lingbo Zhang, a Cold Spring Harbor Laboratory fellow, has made discoveries involving two deadly blood cancers.

In September, Zhang, collaborating with researchers from Memorial Sloan Kettering Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases, found a drug target that might eventually lead to a new treatment for myelodysplastic syndrome, which is a common form of blood cancer. The scientists published their work in the journal Science Translational Medicine.

In January, Zhang published work that analyzed the genes that are active in acute myeloid leukemia, which has a five-year survival rate of only 33 percent. 

By studying 230 genes, Zhang found that this form of blood cancer is addicted to higher concentrations of vitamin B6, creating a potential target for future therapy. The CSHL scientist published this work in the journal Cancer Cell.

“We feel humbled that we found a target” for a future AML therapy, Zhang said of his latest discovery. “My lab partners and I think one day we can potentially translate our knowledge into a real therapy. The translational part gives us the energy and encouragement to work hard.”

Indeed, Zhang explained that his work broadly focuses on blood cancer, in which he looks for questions of medical importance. With MDS, he started with the view that many patients with this disease do not respond to the typical treatment using a hormone called erythropoietin, or EPO.

Lingbo Zhang

People with MDS typically have too few red blood cells, which are made in bone marrow. The hormone EPO converts progenitor immature versions of red blood cells into the ones that function in the body. A small percentage of MDS patients, however, respond to EPO. This occurs because people with this disease have a smaller pool of progenitor cells.

Zhang and his colleagues went upstream of those progenitor cells, searching for defective processes earlier in the pathway. They found that a protein receptor, CHRM4, decreases the production of cells that might become red blood cells. 

By inhibiting that receptor, they hoped to restore the red blood cell making process. In mice that have the same blood features as human MDS, this approach worked, restoring the machinery that leads to the production of red blood cells.

With both the MDS and the leukemia studies, these discoveries might lead to a future treatment, but are not necessarily the final step between understanding molecular signals and developing treatments. These findings are transitioning from basic discoveries into the preclinical development of novel therapies, Zhang said.

For MDS, the treatment may be effective with the inhibitor itself, while for AML, it will potentially be effective as part of a therapy in combination with other treatments.

In his work on leukemia, Zhang said the research went through several phases, each of which took several months. For starters, he screened all the potential target genes. Once he performed the initial work, he conducted a validation study, exploring each gene, one by one. Finally, he worked to validate the study.

After all that work, he discovered the role that the gene that makes PDXK, the enzyme that helps cells use vitamin B6, plays in contributing to cancer. Normal, healthy cells use vitamin B6 during metabolism to produce energy and grow. As with most cancers, leukemia involves more cell division than in a healthy cell, which means that the PDXK enzyme is more active.

Scott Lowe, a collaborator on the research and former CSHL fellow who is now the chair of Cancer Biology and Genetics at Memorial Sloan Kettering, expressed surprised at the finding. “While the action of certain vitamins has previously been linked to cancer, the specific links between vitamin B6 identified here were unexpected,” he said in a press release.

A postdoctoral researcher in Zhang’s lab who has been working on the project for two years, Bo Li plans to continue this research and hopes to find a more mechanistic understanding of the discovery.

While this vitamin contributes to cancer, people with leukemia shouldn’t reduce their consumption of B6, which is necessary in healthy cells. If normal and cancer cells both need this vitamin, how could this be a target for drugs?

The difference, Zhang explained, is in the concentration of the enzyme and, as a result, the B6.

PDXK is higher in leukemia. Reducing its activity by inhibiting this activity could affect the disease.

Working with a collaborator at Memorial Sloan Kettering, Zhang is hoping to develop a better chemical compound with the right property to target the activity of this gene and enzyme.

To conduct research into different diseases and pathways, Zhang works with a group of “very talented and hard working people,” in his lab, which includes a few postdoctoral researchers, a doctoral student, a few undergraduates and a technician, bringing his lab’s staff to eight people. “We also have very good collaborators at other institutes and we are able to manage several projects in parallel,” he said.

Zhang said he likes basic and translational science. The basic science brings “beautiful new theories that identify a detail nature created.” He also feels driven to “translate some of these basic discoveries into a potential treatment,” he said. He is working with a foundation and the hospital and receives patient information from them, which encourages him to work hard to seek ways to “benefit them.”

Down the road, he hopes to understand the hierarchical process that leads from stem cells to mature blood cells. By identifying a majority of the players or the regulators, he may be able to understand the different processes involved in the course of numerous diseases.

As for his current work, Zhang is pleased with the potential translational benefit of both discoveries. “I feel very happy that we can identify a target for leukemia and MDS,” he said.

From left, Martin Kaczocha, Robert Rizzo, Iwao Ojima and Lloyd Trotman. Photo from SBU

By Daniel Dunaief

Pulling together experts from a variety of fields, scientists at Stony Brook University and Cold Spring Harbor Laboratory have demonstrated promise in their efforts to tackle prostate cancer in a new way.

Led by Iwao Ojima, a distinguished professor of chemistry and director of the Institute of Chemical Biology and Drug Discovery at SBU, and Martin Kaczocha, an assistant professor in the Department of Anesthesiology at SBU, the multidisciplinary team recently received a five-year, $4.2 million grant from the National Cancer Institute.

The team is following up on its preliminary success with inhibitors of fatty acid binding protein 5, or FABP5. By tamping down on this protein in prostate cancer cells grown in the lab and in mouse models of the disease, these researchers treated metastatic cancer cells.

The scientists, who received a Translational Research Opportunities Seed Grant from the Renaissance School of Medicine at Stony Brook, were pleased with the next steps in their research.

“We’re happy that the National Cancer Institute validated our target,” said Kaczocha. It will help us “move forward and expand the scope of our work.”

From left, Robert Rizzo, Iwao Ojima, Martin Kaczocha and Lloyd Trotman. Photo from SBU

To be sure, scientists are generally cautiously optimistic about the translation between basic discoveries about mechanisms involved in cancer and the ability of doctors to use these findings in future therapies. Indeed, numerous promising early efforts haven’t always led to treatments. “Many tumors develop resistance to existing therapies through a variety of mechanisms,” said Kaczocha.

Still, the researchers involved in the current study hope the findings will eventually provide another tool in the treatment of prostate cancer.

The inhibitors scientists including Lloyd Trotman, a professor at Cold Spring Harbor Laboratory, are testing “appear to work in a context where [other treatments] lose efficacy. We hope this will translate” to a setting in which the researchers test their treatment in a mouse model of prostate cancer, explained Kaczocha. One of the goals of the NCI grant is to find further validation of this benefit.

Eventually, any possible treatment that utilizes these findings would involve a combination of inhibitors and existing therapeutics, Kaczocha said.

To create a product that might target this molecule, Ojima screened more than one million commercially available compounds on a computer. Out of over 1,000 compounds designed and analyzed, he selected about 120 for chemical synthesis and biological assay.

Artificial intelligence helps dig out known matters from a huge data, but not for newly created substances. Ojima found more than 30 compounds from the ones he synthesized and tested that were more advanced than the original project.

“It’s an ongoing process,” Ojima explained, adding that he believes he will find a more efficacious inhibitor. Ojima and Kaczocha are working with Robert Rizzo, a professor in the Department of Applied Mathematics & Statistics at SBU to develop these inhibitors.

Indeed, that process involves determining the stability, bioavailability and many other factors to minimize any adverse side effects

The side effects from this treatment connect to the original focus of the scientific team. As it turns out, inhibiting FABP5 causes pain relief because it reduces the breakdown of anandamide, or AEA, which is part of the body’s natural pain relief system. The inhibitors also have anti-inflammatory properties.

“This compound’s side effect is pretty beneficial for patients,” said Ojima.

The Long Island team is continuing to pursue the use of these compounds to manage pain as well.

Indeed, Kaczocha’s mother Zofia, who has pain associated with arthritis, asks him at least once a month when his drug will be available. The NCI grant will enable him and his colleagues to continue to build on their earlier work as they hope to translate their scientific discoveries into a clinical option.

“We are continuing our original research on the use of FABP5 inhibitors for pain control,” Ojima explained in an email.

As for their work with cancer, the inhibitors are “less cytotoxic,” Ojima said, and, in animal models, have been able to kill metastatic cancer cells that have become resistant to drug treatment. He suggested that the hope of this treatment is that it can sensitize the cancer cells or tumor to other therapies, which is a “promising approach.”

So far, Ojima, Kaczocha, Trotman and colleagues have tested this treatment only on tumors that haven’t yet metastasized, and not on tumors that have spread to other organs. “Our hope is that it may have some preventive effect in the early stages” of metastasis, Ojima said.

Ojima and Kaczocha were grateful for the seed grant from the medical school, which helped push the research forward. “A seed grant is very important for basic research,” Ojima added.

Other cancers, such as breast cancer, also have over expression of the same fatty acid binding protein. While the scientists are starting with prostate cancer, they hope to expand their work to other cancers as well, once they start gathering results.

La Jolla, California-based Artelo Biosciences partnered with these researchers starting in the spring of 2018. Artelo is licensing the patents for the target as well as the patents for lead compounds. Moving any compound through the beginning of the Food & Drug Administration testing is something Artelo will eventually take over, Kaczocha said. “They will have the financing to pursue this further,” he added.

As a researcher and a pharmacologist who is involved in basic and translational studies, Kaczocha said his hope is always to develop something in his career that will help patients.

Other research groups are also developing small molecule inhibitors to reduce the prevalence or activity of fatty acid binding proteins, but these other scientists have generally not focused on the role of these proteins in cancer. Fatty acid binding protein 4, for example, has a role in metabolic disorders.

“We have a relatively unique position where we are targeting prostate cancer” by reducing the activity and effect of this protein, Kaczocha said.

Trotman, whose lab has a unique animal model of prostate cancer that is a close mimic to the progression of prostate cancer in humans, offers an advantage in their research work, added Kaczocha.

 

Robert Cushman Murphy Jr. High School (team one), from left, coach Jillian Visser, Jayden Chandool, Michael Melikyan, Michaelangelo Scialabba, Rithik Sogal, Kevin Shi and coach Emily Chernakof

On Thursday, Jan. 30 and Friday, Jan. 31, the U.S. Department of Energy’s Brookhaven National Laboratory held two back-to-back installments of the Long Island Science Bowl, a regional branch of DOE’s 30th annual National Science Bowl®. In this fast-paced question-and-answer showdown, teams of students from across Long Island were tested on a range of science disciplines including biology, chemistry, Earth science, physics, energy and math.

On Thursday, Team One of Great Neck South Middle School garnered first place in the middle school competition, earning their school three years of consecutive wins. Team Three of Great Neck Middle School captured second place; Robert Cushman Murphy Jr. High School (team one) of Stony Brook won third place; and Commack Middle School (team one) placed fourth.

On Friday, top honors went to Great Neck South High School, who competed against 19 other teams in the high school competition. High school runners-up included Wheatley School in Old Westbury (second place); Ward Melville High School in E. Setauket (third place); and Comsewogue High School in Port Jefferson Station (fourth place). 

As first place winners, Great Neck South Middle School (team one) and Great Neck South High School have won all-expenses-paid trips to the National Finals near Washington, D.C., which will begin on April 30. They’ll be joined by the winners of all 112 regional competitions held across the country.

“The National Science Bowl® continues to be one of the premier academic competitions across the country, preparing America’s next-generation for future success in the ever-expanding fields of science, technology, and engineering,” said U.S. Secretary of Energy Dan Brouillette. “The Department of Energy is committed to fostering opportunities for our nation’s students, and we congratulate Great Neck South in advancing to the National Finals, where they will continue to showcase their talents as the top minds in math and science.”

All participating students received a Science Bowl T-shirt and winning teams also received trophies and medals, and the top four high school teams received cash awards. Prizes were courtesy of Teachers Federal Credit Union and Brookhaven Science Associates (BSA), the event’s sponsors. BSA is the company that manages and operates Brookhaven Lab for DOE.

For more information, visit https://energy.gov/science. 

Peng Zhang, center, with four of his students from his power systems class, from left, Marissa Simonelli, Ethan Freund, Kelly Higinbotham and Zachary Sola, who were selected as IEEE Power and Engergy Scholars in 2017. Photo by Mary McCarthy

By Daniel Dunaief

If Peng Zhang succeeds in his work, customers on Long Island and elsewhere will no longer lose power for days or even hours after violent storms.

One of the newest additions to the Department of Electrical and Computer Engineering at Stony Brook University, Zhang, who is the SUNY Empire Innovation associate professor, is enhancing the resiliency and reliability of microgrids that may be adaptable enough to provide energy to heat and light a home despite natural or man-made disruptions. Unlike the typical distributed energy network of most utilities around the country, microgrids are localized and can function on their own.

Peng Zhang. Photo from SBU

A microgrid is a “central theme of our research,” said Zhang, who joined Stony Brook at the beginning of September. “Even when a utility grid is down because of a hurricane or an attack, a microgrid is still able to supply the local customers” with power. He is also using quantum information science and quantum engineering to empower a resilient power grid.

Zhang expects that the microgrid and utility grid will be more resilient, stable and reliable than the current system. A microgrid will provide reliable power even when a main grid is offline. The microgrid wouldn’t replace the function of the grid in the near future, but would enhance the electricity resilience for customers when the central utility is unavailable or unstable.

Part of his motivation in working in this field comes from his own experience with a weather-related loss of power. 

Even though Zhang, who used his training in mathematics to develop an expertise in power systems, had been working on wind farms and their grid integration, he decided after Hurricane Irene and a nor’easter that he should do more research on how to restore power after a utility became unavailable.

Irene hit in August, while the nor’easter knocked out power in the winter. After the storms, Northeast Utilities, which is currently called Eversource Energy, asked him to lead a project to recommend solutions to weather-induced outages.

Zhang plans to publish a book through Cambridge University Press this year called “Networked Microgrids,” which not only includes his previous results but also presents his vision for the future, including microgrids that are self-healing, self-protected, self-reconfiguring and autonomous.

He recognizes that microgrids, which are becoming increasingly popular in the energy community, present a number of challenges for customers. For starters, the cost, at this point, for consumers can be prohibitively high.

Zhang can cut those expenses, however, by replacing hardware upgrades with software, enabling more of the current system to function with greater resilience without requiring as many costly hardware modifications.

His National Science Foundation project on programmable microgrids will last until next year. He believes he will be able to verify most of the prototypes for the programmable microgrid functions by then.

Zhang called advances in energy storage a “key component” that could improve the way microgrids control and distribute power. Energy storage can help stabilize and improve the resilience of microgrids.

He is eager to work with Esther Takeuchi, who has dual appointments at Stony Brook University and Brookhaven National Laboratory, not only on microgrid technologies but also on renewable integration in the transmission grid.

Zhang appreciates SBU’s reputation in physics, applied math, computer science and electrical and computer engineering. When he was young, he said he also heard about and saw Chen-Ning Yang, whom he described as a model and legend.

“I feel proud and honored to be working at Stony Brook where Dr. Yang taught for more than three decades,” he stated in an email.

In his lab, Zhang has six doctoral students, one visiting doctoral student and two master’s students. A postdoctoral researcher, Yifan Zhou, who worked with him at the University of Connecticut, will soon join his Long Island lab.

Zhang, who earned doctorates from Tsinghua University and the University of British Columbia, brought along a few grants from the University of Connecticut where he held two distinguished titles.

Zhang has “high expectations for the people who work for him,” Peter Luh, a board of trustees distinguished professor at the University of Connecticut, explained in an email. “However, he is considerate and helps them achieve their goals.”

Zhou, who comes from Tsinghua University, is working with him on stability issues in microgrids to guarantee their performance under any possible scenario, from a major storm to a cyberattack.

Zhang is working with Scott Smolka and Scott Stoller, both in the Computer Science Department  at Stony Brook, on resilient microgrids

“We are planning to use simulations and more rigorous methods for formal mathematical analysis of cyberphysical systems to verify resiliency properties in the presence of fault or attacks,” said Stoller who described Zhang as a “distinguished expert on electric power systems and especially microgrids. His move to Stony Brook brings significant new expertise to the university.”

The Stony Brook scientists have created an exercise in which they attack his software systems, while he tries to ensure its ongoing reliability. Zhang will develop defense strategies to guarantee the resilience and safety of the microgrids.

Zhang was born in Shandong Province in China. He is married to Helen Wang, who works for a nonprofit corporation as an electrical engineer. The power couple has three sons: William, 13, Henry 10, and Benjamin, 8. They are hoping their sons benefit from the public school system on Long Island.

Zhang’s five-year goal for his work involves building an institute for power engineering, which will focus on microgrids and other future technologies. This institute could have 20 to 30 doctoral students.

An ambitious researcher, Zhang would like to be the leader in microgrid research in the country. “My goal is to make Stony Brook the top player in microgrid research in the U.S.,” he said.

Meng Yue, scientist in the Sustainable Energy Technologies Department at Brookhaven National Laboratory who has been collaborating with Zhang for over five years, anticipates that Zhang’s research will help consumers.

“As New York State has more aggressive renewable portfolio, I believe the research achievements will soon advance technologies in the power grid application,” he said.

 

Adam Singer. Photo from SBU

By Daniel Dunaief

A patient comes rushing into the emergency room at a hospital. He has numerous symptoms and, perhaps, preexisting conditions, that the staff gather together as they try to stabilize him and set him back on the path toward a healthy life.

Emergency room protocols typically involve testing for the function of major organs like the heart, even as a patient with diabetes would also likely need a blood sugar test as well.

For a specific subset of patients, hyperkalemia, in which a patient has potentially dangerously elevated levels of the element potassium, may also merit additional testing and treatment.

Adam Singer with his son Daniel. Photo by Michael Beck

In a recent study in the American Journal of Emergency Medicine, Adam Singer, a professor and vice chair for research at the Department of Emergency Medicine at the Renaissance School of Medicine at Stony Brook University, found that mortality rates were cut in half when doctors corrected for high levels of potassium.

“This study was focused on what we could do” to help patients with hyperkalemia, Singer said. “We always knew that rapid normalization was important, but we did not have the evidence except for anecdotal cases.”

Examining about 115,000 hospital visits to the Stony Brook Emergency Department between 2016 and 2017, Singer and his colleagues found that the mortality rate fell to 6.3 percent from 12.7 percent for patients whose potassium level was normalized.

Singer is “tackling a topic which is very important, which is life threatening and for which there is no clear standard,” said Peter Viccellio, a professor and vice chairman in the Department of Emergency Medicine at the Renaissance School of Medicine at SBU.

Viccellio said Stony Brook has become “more conservative over the last couple of years in treating patients with lower levels” of potassium.

One of the challenges with hyperkalemia is that it doesn’t usually come with any tell-tale symptoms. Emergency room doctors can’t determine an elevated level of potassium by looking at a patient or by hearing a list of symptoms.

Sometimes, people with hyperkalemia show weakness, nausea or vomiting, but those three conditions are also present in numerous other medical challenges.

Singer said not all the patients died directly from hyperkalemia. Most people with hyperkalemia have significant co-morbidities that put them at risk from other causes. Nonetheless, the higher level of mortality for patients above a threshold for potassium suggests that evaluating patients not only should include an awareness of the amount of this element in the blood, but also a clear set of guidelines for how to reduce it.

“This strengthens the need to call for more evidence-based studies to figure out the best and most effective therapies,” Singer said. “The higher the level of potassium, the greater the urgency for rapid correction,” he added.

Some hospitals may be using point-of-care tests and newer medications, especially new potassium binders. These treatments, however, have not been studied in large numbers yet.

As the population ages, more chronic disease patients take medicines that affect potassium levels. This, in turn, increases the risk of hyperkalemia, in part because chronic conditions like diabetes are so common. This risk extends to people who are obese and are developing diabetes.

On the positive side, Singer said some hospitals are using rapid point-of-care testing and, when they discover evidence of higher potassium, are using a new class of medications that treats the condition.

While the urgency for emergency room attendants is high enough to add potassium tests, especially for vulnerable patients, Singer does not believe that first responders necessarily need to add these tests to their evaluations on the way to the hospital. Such testing might be more urgent in rural areas, where transportation to a medical facility would take more time.

“Generally, such testing is not going to make a big difference” because patients will arrive at the hospital or medical facility before hyperkalemia becomes a contributing factor in their health, said Singer.

Changing a person’s lifestyle to lower the risk of hyperkalemia can be difficult because diets that are low in potassium are “hard to follow,” he said. Additionally diets that are low in potassium are often “lacking in other important food contents.”

Patients who are prone to hyperkalemia include people who are dehydrated, have kidney disease and missed a dialysis treatment, or are taking medications that can, as a side effect, boost the amount of potassium.

Generally, people don’t suddenly develop a high risk for hyperkalemia without any past medical history that suggests they are susceptible to it. During annual physicals, doctors customarily test for the level of potassium in the blood.

In terms of the total emergency room population, about 1 percent have higher potassium. During the years of the study, 308 patients had elevated potassium levels that remained high, while 576 had potassium levels that were high, but that were stabilized through treatment.

Higher potassium levels don’t necessarily require immediate treatment, in part because of a person who vomited several times might be getting fluids that restore the potassium balance

As director of research, Singer balances between his clinical responsibilities and his interest in conducting scientific research. When he sees an issue in the clinic, he can go back to the lab and then translate his research into clinical practice.

Viccellio said Singer is “internationally renowned” as a researcher and that he was a “superstar from day one.” 

Singer’s primary interests are in acute wound care and burns. He has recently been studying a new, minimally invasive, nonsurgical technique to remove dead tissue after burns that involves an enzymatic agent and has been involved in several promising clinical trials of this technique.

Viccellio said Singer has done “fantastic work” on cosmetic repair of facial lacerations. Viccellio also suggested that Singer was “like the Bill Belichick” of research, helping numerous other people who went on to become research directors at other institutions.

A resident of Setauket for the last quarter of a century, Singer and his wife, Ayellet, have three children. Following in his father’s footsteps, his son Daniel is finishing his residency in emergency medicine at Stony Brook. 

While Singer was born in Philadelphia and lived in Israel for part of his life, including during medical school, he has roots on Long Island. His grandparents originally lived in Ronkonkoma. Singer Lane in Smithtown, which was named after his realtor grandfather Seymour Singer, includes the one-room schoolhouse where Walt Whitman was a schoolmaster. 

As for his work on hyperkalemia, Singer is pleased with the way he and his colleagues at Stony Brook have contributed to an awareness of the dangers of this condition. “We are identifying these patients and treating them,” he said.