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Daniel Dunaief

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Michael Schatz. Photo courtesy of Cold Spring Harbor Laboratory

By Daniel Dunaief

What if an enormous collection of Scrabble letters were spread out across the floor? What if several letters came together to form the word “victory”? Would that mean something? On its own, the word might be encouraging, depending on the context.

Genetic researchers are constantly looking at letters for the nucleotides adenine, guanine, cytosine and tyrosine, searching for combinations that might lead to health problems or, eventually, diseases like cancer.

For many of these diseases, seeing the equivalent of words like “cancer,” “victory” and “predisposition” are helpful, but they are missing a key element: context.

W. Richard McCombie

Michael Schatz, an adjunct associate professor at Cold Spring Harbor Laboratory who is also the Bloomberg distinguished associate professor at Johns Hopkins, and W. Richard McCombie, a professor at Cold Spring Harbor Laboratory, use long-read sequencing technology developed by Pacific Biosciences to find genetic variants that short-read sequencing missed.

The two scientists recently teamed up to publish their work on the cover of the August issue of the journal Genome Research. They provided a highly detailed map of the structural variations in the genes of a breast cancer cell.

“This is one of many covers [of scientific journals] that we are pleased and proud of,” said Jonas Korlach, the chief scientific officer at Menlo Park, California-based Pacific Biosciences. 

“This is another example of how long-read sequencing can give you a more complete picture of the genome and allow researchers to get a more complete understanding of the underlying biology and here, specifically, that underlies the transition from a health to a cancer disease state,” he said.

Schatz and McCombie were able to see fine detail and the context for those specific sequences. They were able to see about 20,000 structural variations in the cancer genome. “It’s like using Google maps,” explained Schatz in a recent interview. “You can see the overall picture of the country and then you can see roads and zoom out.”

In the context of their genetics work, this means they could see large and small changes in the genome. Only about a quarter of the variants they found could be detected without long-read technology.

In breast cancer, scientists currently know about a family of genes that could be involved in the disease. At this point, however, they may be unaware of other variants that are in those genes. Schatz is hoping to develop more sensitive diagnostics to identify more women at risk.

People like actress and advocate Angelina Jolie have used their genetic screens to make informed decisions about their health care even before signs of any problems arise. Jolie had a double mastectomy after she learned she had the mutation in the BRCA1 gene that put her at an 87 percent risk of developing breast cancer.

By studying the sequence of genes involved in breast cancer, researchers may be able to identify other people that are “at high risk based on their genetics,” Schatz said.

Knowing what’s in your genome can help people decide on potentially prophylactic treatments. 

When people discover that they have breast cancer, they typically choose a specific type of treatment, depending on the subtype of cancer.

“There’s a lot of interest to divide [the genetic subtypes] down into even finer detail,” said Schatz, adding, “There’s also interest in transferring those categories into other types of cancer, to give [patients] better treatments if and when the disease occurs.”

The reduced cost of sequencing has made these kinds of studies more feasible. In 2012, this study of the breast cancer genome would have cost about $100,000. To do this kind of research today costs closer to $10,000 and there’s even newer sequencing technology that promises to be even less expensive, he said.

Pacific Biosciences continues to see a reduction in the cost of its technology. The company plans to introduce a new chip next year that has an eightfold higher capacity, Korlach said.

Schatz said the long-term goal is to apply this technique to thousands of patients, which could help detect and understand genetic patterns. He and McCombie are following up on this research by looking at patients at Northwell Health.

In this work, Schatz’s group wrote software that helped decipher the code and the context for the genetic sequence.

“The instrument doesn’t know anything about genes or cancer,” he said. “It produces raw data. We write software that can take those sequences and compare them to the genome and look for patterns to evaluate what this raw data tells us.”

Schatz described McCombie, with whom he speaks every day or so, as his “perfect complement.” He suggested that McCombie was one of the world’s leaders on the experimental side, adding, “There’s a lot of artwork that goes into running the instruments. My lab doesn’t have that, but his lab does.”

Working with his team at CSHL and Johns Hopkins has presented Schatz with numerous opportunities for growth and advancement.

“Cold Spring Harbor is an internationally recognized institute for basic science, while Johns Hopkins is also an internationally recognized research hospital and university,” he explained. He’s living in the “best of both worlds,” which allows him to “tap into amazing people and resources and capacities.”

Korlach has known Schatz for at least a decade. He said he’s been “really impressed with his approach,” and that Schatz is “highly regarded by his peers and in the community.”

Schatz is also a “terrific mentor” who has helped guide the development of the careers of several of his former students, Korlach said.

Down the road, Schatz also hopes to explore the genetic signature that might lead to specific changes in a cancer, transforming it from an organ-specific disease into a metastatic condition.

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From left, Peter Tonge with Eleanor Allen and Fereidoon Daryaee. Photo from SBU

By Daniel Dunaief

The journey begins at one point and ends at another. What’s unclear, however, is the process that led from beginning to end. That’s where Peter Tonge, a professor in the Department of Chemistry and Radiology at Stony Brook University’s College of Arts & Sciences, recently discovered important details.

Working with a protein called dronpa, Tonge wanted to know how the protein changed configurations as it reacted to light. There was more than one theory on how this process worked, Tonge said. “Our studies validated one of the previous hypotheses,” he said. Structural changes occur on different time scales. With a team of collaborators, Tonge was able to follow the photoreaction from absorption to the final activated form of the photoreceptor.

The technique Tonge used is called infrared spectroscopy. Through this approach, he looks at the vibration in molecules. People generally “have this picture of a molecule that isn’t moving,” he said. “In fact, atoms in the molecule are vibrating, like balls on a spring going backwards and forwards.”

Tonge uses the technique to look at vibrations before and after the absorption of light and subtracts the two. “People knew what the structure of dronpa was at the beginning and they knew the final structure,” but they had only developed educated theories about the transition from one state to another, he explained. The application of this work isn’t immediate.

“The knowledge we gained will be a foundation that will be combined with other knowledge,” Tonge said. Theoretically, scientists or drug companies can redesign the protein, fine-tuning its light-sensitive properties.

Tonge’s lab, which includes 11 graduate students, two postdoctoral researchers, two undergraduates and six high school students, explores several different scientific questions. They are studying how proteins use the energy in a photon of light to perform different biological functions.

In optogenetics, scientists have developed ways to use light to turn processes on or off. Eventually, researchers would like to figure out ways to control gene transcription using this technique. According to Tonge, scientists are “interested in using these processes that have naturally evolved to tailor them to our own purposes.”

Tonge’s other research focus involves understanding how drugs work. Most drugs fail when they reach clinical trials. “Our ability to predict how drugs will work in humans needs to be improved,” he said, adding that he focuses on something called the kinetics of drug target interactions to improve the process of drug discovery.

In kinetics, he explores how fast a drug binds to its target and how long it remains bound. Companies look to design drugs that remain bound to their desired target for longer, while separating from other areas more rapidly. This kind of kinetic selectivity ensures the effectiveness of the drug while limiting side effects.

By thinking about how long a drug binds to its target, researchers can “improve the prediction of drug activity in humans,” explained Tonge. “We need to consider both thermodynamics and kinetics in the prediction of drug activity.”

A study of kinetics can allow researchers to consider how drugs work. Understanding what causes them to break off from their intended target can help scientists make them more efficient, reducing their failure rate.

Borrowing from sports, Tonge suggested that kinetics measures how quickly an outfielder catches a ball and throws it back to the infield, while thermodynamics indicates whether the outfielder will be able to make a catch. He believes the most interesting work in terms of kinetics should occur in a partnership between academia and industry.

Tonge is the newly appointed director of the Center for Advanced Study of Drug Action at Stony Brook, where he plans to develop a fundamental understanding of how drugs work and the role kinetics play in drug action.

Joanna Fowler, a senior chemist emeritus at Brookhaven National Laboratory, worked with Tonge for several years starting in 2005. She said Tonge developed ways to label tuberculosis and other molecularly targeted molecules he had developed in his lab. They did this to image and follow it in the body using the imaging tools BNL had at the time.

In an email, she described Tonge as a “scholar” and a “deep thinker,” who investigates mechanisms that govern the interactions between chemical compounds including drugs and living systems, adding, “He uses his knowledge to address problems that affect human beings.”

Finally, Tonge is also pursuing research on positron emission tomography. He would like to synthesize new radio tracers and use PET to see where they go and learn more about how drugs work. He would also like to enhance ways to locate bacteria in humans.

The professor is trying to detect infections in places where it is difficult to diagnose because of the challenge in getting clinical samples. Samples from throat cultures or mucus are relatively easy to obtain — the short-term agony from a swab in the back of the throat notwithstanding.

“It is more difficult to get samples from locations such as prosthetic joints,” which makes it more challenging to detect and diagnose, he said.

If an infection isn’t treated properly, doctors might have to remove the prosthesis. Similarly, bone infections are difficult to detect and, if left unchecked, can lead to amputations.

A resident of Setauket, Tonge lives with his wife, Nicole Sampson, who is a professor in the chemistry department at SBU and is the interim dean for the College of Arts and Sciences, and their two children, Sebastian, 18, and Oliver, 14.

Tonge, who was raised in the United Kingdom, said he enjoys running on Long Island.

Tonge and Sampson are co-directors of a graduate student training program in which they train students to improve their ability to communicate their science. One of the activities they undertook was to visit a high school and have grad students present their research to high school students.

As for his work, Tonge said he is “genuinely curious about the chemistry that occurs in biological systems.”

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Kenneth Shroyer and Luisa Escobar-Hoyos are the recent recipients of a two-year research grant from PanCAN. Photo by Cindy Leiton

By Daniel Dunaief

Stony Brook University has collected its first PanCAN award. Pathology Chair Kenneth Shroyer and Assistant Professor and Co-Director of the Pathology Translational Research Lab Luisa Escobar-Hoyos have earned a two-year $500,000 research grant from the Pancreatic Cancer Action Network.

The tandem has worked together for seven years on the protein keratin 17, or k17, which started out as an unlikely participant in pancreatic cancer and as a molecule cancer uses to evade chemotherapy.

Shroyer and Escobar-Hoyos were “thrilled to get the award,” said Shroyer in a recent email. “While we thought our proposal was very strong, we knew that this was a highly competitive process.”

Indeed, the funding level for the PanCAN grants program was between 10 and 15 percent, according to PanCAN.

The grants review committee sought to identify projects that “would constitute novel targets for treating pancreatic cancer,” said Maya Bader, the associate director of scientific grants at PanCAN. 

“Given that k17 represents a potential new target, the committee felt the project was a good fit with exciting potential to meet this goal. We are thrilled to welcome Dr. Shroyer to the PanCAN grantee research community and look forward to following both his and Dr. Escobar-Hoyos’ contributions to the field,” she said.

Escobar-Hoyos explained that she and Shroyer hope “this work will shed scientific insight into potential novel ways to treat the most aggressive form of pancreatic ductal adenocarcinoma,” which is the most common type of pancreatic cancer.

Although they are not sure if their approaches will be successful, she believes they will provide information that researchers can use to “further understand this aggressive disease.”

Thus far, Shroyer and Escobar-Hoyos have focused on the role of k17 in pulling the tumor suppressor protein p27 out of the nucleus into the cytoplasm, where it is degraded. More recently, however, they have explored how the k17 the tumor produces reprograms the cancer metabolome.

They have data that suggests that k17 impacts several dozen proteins, Escobar-Hoyos suggested. If the tumors of patients express k17, around half the protein content will go to the nucleus of the cell. 

In addition to understanding what k17 does when it enters the nucleus, Escobar-Hoyos and Shroyer are testing how they might stop k17 from entering the nucleus at all. Such an approach may prevent pancreatic cancer from growing.

Shroyer and Escobar-Hoyos are working with a graduate student in the lab, Chun-Hao Pan, who is testing molecular pathways that might make pancreatic cancer more resistant to chemotherapy.

Dr. Yusuf Hannun, the director of the Stony Brook Cancer Center, was pleased that his fellow Stony Brook scientists earned the PanCAN distinction.

“It is an important award and speaks to our growing significant efforts in research in pancreatic cancer,” he said, suggesting that the research could have important benefits for patients battling with pancreatic cancer.

“This defines at the very least a novel and important biomarker for pancreatic cancer that can also extend into novel therapeutic approaches,” Hannun said. This type of research could enhance the diagnostic process, allowing doctors to subtype pancreatic cancers and, if the pathways become clearer, enhance the effect of chemotherapy.

The funds from the PanCAN award will support experiments in cell culture and in animal models of pancreatic cancer, Shroyer explained.

Shroyer has teamed up with numerous researchers at Stony Brook and Cold Spring Harbor Laboratory on this work.

As proof of principle for one aspect of the proposal, he accessed chemosensitivity data from pancreatic cancer organoids. Hervé Tiriac, a research investigator who works in David Tuveson’s lab at CSHL, generated these organoids from SBU pancreatic cancer specimens.

In addition to their work with organoids at CSHL, Shroyer and Escober-Hoyos benefited from their collaboration with SBU’s Ellen Li, a professor of medicine, who ensured patient consent and specimen collection.

Going forward at Stony Brook University, the key collaborator for this project will be Richard Moffitt, an assistant professor in the departments of Biomedical Informatics and Pathology.

Shroyer described Moffitt as an “internationally recognized leader in the field of pancreatic cancer subtyping” who is working to understand better how k17 could serve as a prognostic biomarker.

At the same time, Wei Hou from the Department of Family, Population and Preventive Medicine will provide biostatistical support throughout the course of the project.

PanCAN, which has donated $48 million to support pancreatic cancer research, awarded nine grants this year in the United States, Canada and France, for a total contribution of $4.2 million. 

The other scientists include Andrew Aguirre from the Dana-Farber Cancer Institute, Scott Lowe, who had previously worked at Cold Spring Harbor Laboratory and is now at Memorial Sloan-Kettering Cancer Center and George Miller at New York University School of Medicine.

Previous recipients of PanCAN awards have been able to leverage the funds to attract research dollars to their work.

Grantees who had received $28.2 million from 2003 to 2015 went on to receive $311 million in subsequent funding to support their pancreatic cancer research, according to PanCAN. That means that every dollar awarded by PanCAN converts to $11.01 to fund future research aimed at understanding, diagnosing and treating pancreatic cancer, according to Bader. Most of the subsequent funding comes from government sources.

PanCAN award recipients have published research that other scientists have cited more than 11,000 times in other papers published in biomedical journals. This means “other researchers are reading, learning from and building upon our grantees’ work,” Bader added.

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Stephanie Maiolino. Photo by Elizabeth Anne Ferrer

By Daniel Dunaief

This one’s a head scratcher, literally.

For years, people assumed early primates — small creatures that lived 55 million years ago — had nails. That, however, is not the complete story, as Stony Brook University Assistant Professor Stephanie Maiolino and a team of researchers discovered.

In addition to nails, which lay flat on our fingers and which make it easy to scratch an itch after a mosquito bite, earlier primates had something called grooming claws. These claws, which were on the toes next to their big toes, allowed them to remove external parasites like ticks and lice, which likely helped them survive against an onslaught of various critters eager to steal, or even infect, some of their blood.

Maiolino, who is in the Department of Anatomical Sciences at SBU, teamed up with lead author Douglas Boyer, an associate professor in the Department of Evolutionary Anthropology at Duke University; Johnathan Bloch, the Florida Museum of Natural History curator of vertebrate paleontology at University of Florida; Patricia Holroyd, a senior museum scientist at UC-Berkeley’s  Museum of Paleontology; and Paul Morse, from the Florida Museum of Natural History at the University of Florida at Gainesville to report their results recently in the Journal of Human Evolution.

“It was generally assumed that only a certain type of primate had grooming claws,” Maiolino said. “Finding these structures was quite surprising.”

Maiolino spent considerable time during her doctoral work, which she conducted at SBU prior to becoming an instructor at the university, analyzing the differences in the bones of species that have nails, claws and grooming claws. By understanding the anatomical features of the phalanges — or fingers and toes — leading up to the claws or nails, Maiolino was able to go back into the fossil record to explore the prevalence of these digit protrusions.

Oftentimes, she suggested, researchers collect a bone, or even a fragment of a bone, in which a nail or claw is almost never preserved in the fossil record. Maiolino used her analysis to extrapolate the parts that extend beyond the remaining fossils.

While nails sit on the end of fingers, grooming claws stick up, which puts them in an ideal position for combing through hair, which would allow the primates to remove pests that could compromise their health or threaten their survival.

“From a functional standpoint, it’s often overlooked how important the need to remove these parasites [is],” she said. When people see lemurs whose ears are completely covered in ticks or they hear about dogs that have so many ticks on them that the dog is at risk of dying, they recognize that “having an adaptation to help you remove them is actually surprisingly a big deal.”

Like any other adaptation, however, the development of these grooming digits comes with a cost. Instead of having that digit available for locomotion or grasping branches, it becomes more useful in removing unwanted insects. “There are significant pressures shaping the feet of these primates,” said Maiolino.

To provide some perspective on the importance of grooming claws, Maiolino highlighted how the primates from the fossil record were not much bigger than a mouse. Having less blood because they are smaller than current primates, and dealing with ticks that are closer to their size, suggests that the health consequences of an infestation are much greater.

As primates became more social — interacting with other members of their species and taking turns grooming each other — the pressure to have these grooming claws may have reduced.

Nonetheless, Maiolino said, a few primates that spend hours each day picking ticks off each other in a process called allogrooming still have these claws. “Some of the animals that do have [the claws] groom each other considerably,” she said, which suggests that there is still work to do to understand the evolution of these features.

When Maiolino and her collaborators first started exploring the claws versus nails discussion, they knew that researchers believed anthropoids didn’t have them.

“Now we know that anthropoids did,” she said. “We’re getting more of a sense of the distribution” of these claws.

From here, Maiolino would like to continue to explore the evolutionary trajectory from claw-bearing nonprimates to nail-bearing primates. There are a “lot of questions about why early primates ended up evolving nails in the first place,” she said.

William Jungers, a distinguished professor emeritus at Stony Brook University who was Maiolino’s doctoral thesis adviser, described her as “an outstanding and innovative young scientist with a very bright future as an educator and comparative anatomist.” He said Maiolino uses “cutting edge imaging methods to advance our understanding of primate origins and paleobiology, especially the evolution of unique aspects of primate hands and feet.”

Jungers explained that claws and nails are the “key features linked to both locomotion and social behavior.”

Maiolino, who currently lives in Port Jefferson, said when she visits zoos, she’s always on the lookout for the way primates and other mammals use their nails or claws. She also studies photographs and videos.

When she first started graduate school, Maiolino was much more interested in skulls than in nails. Once she linked nails and claws, however, to questions about primate origins, she became much more interested in them.

Outside of the lab, Maiolino said she enjoys watching horror movies. One of her favorites is the second “Aliens” film in the Signourney Weaver centered franchise. She is also a fountain pen enthusiast.

Back in high school in New Jersey, Maiolino  was especially interested in studying evolution. Embryology and embryological development appealed to her, as she was amazed by how growth in the womb affected what organisms became.

As for her work, a Holy Grail question for her would be to better understand why primates developed nails in the first place. She’s trying to understand the interplay between body size, behavior and other variables that affected these structures.

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Camila dos Santos speaks at the Pershing Square Research Alliance’s Fifth Annual Prize Dinner at the Park Avenue Armory on May 23 with Bill Ackman, co-founder of the Pershing Square Sohn Foundation and CEO of Pershing Square Capital Management, and Olivia Tournay Flatto, the President of the Pershing Square Foundation.

By Daniel Dunaief

They aren’t quite wonder twins, but some day the dedicated work of husband and wife scientists Christopher Vakoc and Camila dos Santos may help people batting against a range of cancers, from leukemia to breast cancer.

An assistant professor at Cold Spring Harbor Laboratory, dos Santos recently won the prestigious and highly coveted Pershing Square Sohn prize. Dos Santos, who studies breast cancer, will receive $200,000 in funds per year for the next three years. She won the same prize her husband, an associate professor at Cold Spring Harbor Laboratory, collected two years earlier for his work using the gene-editing technique CRISPR to study the molecular pathways involved in leukemia.

Dos Santos and Vakoc are the first family of prize winners in the Pershing Square Foundation’s five years of supporting research in the New York area.“The board was very much taken by how original her approach is and how thoughtful she is about it,” said Olivia Tournay Flatto, president of the foundation. “There was a lot of early stage data that would say that the observations she’s making are interesting to pursue, but that the National Institutes of Health would not fund. We felt this was something we wanted to be a part of.”

Dos Santos is studying so-called epigenetic changes that protect women from breast cancer if they become pregnant before they are 25. Women who have pregnancies before that cut-off age have a 30 to 40 percent decrease in breast cancer, even decades after their pregnancy.

Dos Santos has been digging into this process, looking at why some women who are pregnant before this age still develop breast cancer later in life.

The Cold Spring Harbor scientist is exploring how infections block the protective effects of pregnancy. She hasn’t defined the panel of infections that could influence cancer risk before or after pregnancy. The hypothesis in her work is that “the whole process that is fighting inflammation could change the breast cells,” which could “take away the advantage that pregnancy brings.”

If she proves her theory — that changes to inflammation could take away benefits of an early pregnancy — she could define changes to proteins and genes as biomarkers to predict the risk of breast cancer, even in the event of an early pregnancy. One of the challenges in the three-step application process for this prize was to explain to a group of experts how what she’s doing was different from what others are pursuing. Her approach is to look at cells before and during the process of turning into cancer cells. That strategy led to the current hypothesis, which was the basis for her application for this prize.

To study breast cancer, dos Santos recently developed a mouse model in her lab, to see how pregnancy changes pre-malignant lesions. When the mice they are studying have a gene that would turn into cancer, some of them don’t develop cancer if they’ve already been pregnant. Those mice that haven’t been pregnant develop cancer. She uses this mouse model to ask questions about how pregnancy changes a cell such that oncogenes cannot operate to change a cell into a cancer.

“We are not only investigating how prevention works, but we are also learning what signals break that prevention,” dos Santos said.

Dos Santos has used the mouse model experiments to test an unusual element to human breast cancer resistance. Women who reach their second trimester before 25, but don’t give birth to a child, have the same resistance, decades later, to breast cancer. Mice whose pregnancies last through the equivalent of the second trimester also experience similar epigenetic benefits.

She has tested mice who have a pseudo-pregnancy —who have higher pregnancy hormone levels without being pregnant — to see if a similar pregnancy environment would convey the same resistance. “Even in those cases, with no fetus, no embryo, no birth and no nursing, we see that the epigenetics changes,” dos Santos said. The scientist plans to use the funds from this award to perform high-tech experiments, such as single-cell, multiple mouse models and human tissue analysis that she wouldn’t have been able to tackle without the funding.

Dos Santos is grateful for the funding, which she said she wouldn’t have been able to secure through other means based on “the stage we are right now,” she said. The work is “risky” and “provocative,” but it’s also “outside of the box ideas and experiments and approaches.”

When she puts all the variants together, the risky outcome could be beneficial, leading to a better understanding of how to copy or, perhaps, understand nature to try to cure or prevent cancer.

Dos Santos said she learned about the award when she was on a train on the way to Jamaica, where she was catching a flight to Washington, D.C. She said she turned into a “texting machine,” sharing the good news with everyone, including her husband Vakoc, who called her as soon as he saw the news. “He was super happy,” she recalled.

She said Vakoc was particularly helpful in discussing the work and in watching their sons Lucas and Marcus who are 8 and 5, respectively. She also received some unexpected help from him before an extensive seven- to eight-minute finalist screening process.

She asked him about the interview, and he remembered that there were five people in the audience and that he didn’t get that many questions. When she appeared for her interview, she saw about 25 people in the audience and received numerous questions. In a way, she said, his memory of his experience may have helped her, because she didn’t have time to worry about the size of the audience or the number of questions.

Dos Santos said their sons are proud of their parents for winning awards for their work on cancer.

When her sons are upset with dos Santos, they sometimes warn, reflecting their parents’ threat to take away TV, that they’re going to “take your epigenetics away.”

Dos Santos said the couple maintains a healthy work-life balance. She is grateful for her husband’s support, as well as for the environment and expertise at Cold Spring Harbor Laboratory.

“Here at the lab, we not only have the technology to move this forward, but we also have a pretty outstanding body of scientists that are very collaborative,” she said.

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By Daniel Dunaief

Replacing batteries in a flashlight or an alarm clock requires simple effort and generally doesn’t carry any risk for the device. The same, however, can’t be said for battery-operated systems that go in human bodies and save lives, such as the implantable cardiac defibrillator, or ICD.

Earlier versions of these life-saving devices that restore a normal heart rhythm were large and clunky and required a change of battery every 12 to 18 months, which meant additional surgeries to get to the device.

Esther Takeuchi with Michaëlle Jean, the secretary general of the Organisation Internationale de la Francophonie, and moderator Fernando Tiberini at the award ceremony in Paris on June 7. Photo courtesy of European Patent Office

That’s where Esther Takeuchi, who is now Stony Brook University’s William and Jane Knapp Endowed Chair in Energy and the Environment and the chief scientist of the Energy Sciences Directorate at Brookhaven National Laboratory, has made her mark. In the 1980s, working at a company called Greatbatch, Takeuchi designed a battery that was much smaller and that lasted as long as five years. The battery she designed was a million times higher power than a pacemaker battery.

For her breakthrough work on this battery, Takeuchi has received numerous awards. Recently, the European Patent Office honored her with the 2018 innovation prize at a ceremony in Paris. Numerous high-level scientists and public officials attended the award presentation, including former French Minister of the Economy Thierry Breton, who is currently the CEO of Atos, and the Secretary General of the International Organisation of Francophony Michaëlle Jean. 

Takeuchi was the only American to win this innovation award this year.

Takeuchi’s work is “the epitome of innovation, as demonstrated in this breakthrough translational research for which she was recognized,” Dr. Samuel L. Stanley Jr., the president of Stony Brook and board chair of Brookhaven Science Associates, which manages Brookhaven National Laboratory. “Her star keeps getting brighter, and I’m proud that she is part of the Stony Brook University family.”

As a winner of this award, Takeuchi joins the ranks of other celebrated scientists, including Shuji Nakamura, who won the European Inventor Award in 2007 and went on to win the Nobel Prize in physics, and Stefan Hell from Germany, whose European Inventor Award predated a Nobel Prize in chemistry. 

Among the over 170 innovators who have won the award, some have worked on gluten substitutes from corn, some have developed drugs against multi-drug-resistant tuberculosis, and some have developed soft close furniture hinges.

“The previous recipients have had substantial impact on the world and how we live,” Takeuchi explained in an email. “It is incredible to be considered among that group.” Nominated for the award by a patent examiner from the European Patent Office, she described the award as an “honor” for the global recognition.

The inventor award is a symbolic prize in which the recipients receive attention for their work, explained Rainer Osterwalder, the director of media relations at the European Patent Office.

Takeuchi was one of four women to receive the award this year — the largest such class of women innovators.

“It was very meaningful to see so many accomplished women be recognized for their contributions,” she explained. “I was delighted to meet them and make some additional contacts with female innovators as well.”

About half the researchers in her lab, which currently includes three postdoctoral researchers and usually has about 12 to 16 graduate students, are women. Takeuchi has said that she likes being a role model for women and that she hopes they can see how it is possible to succeed as a scientist.

Implantable cardiac defibrillators are so common in the United States that an estimated 10,000 people receive them each month.

Indeed, while she was at the reception for an awards ceremony attended by over 600 people, Takeuchi said she met someone who had an ICD.

“It is very rewarding to know that they are alive due to technology and my contributions to the technology,” she explained.

Takeuchi said that many people contributed to the battery project for the ICD over the years who were employed at Greatbach. These collaborators were involved in engineering, manufacturing, quality and customer interactions, with each aspect contributing to the final product.

The battery innovation stacks alternating layers of anodes and cathodes and uses lithium silver vanadium oxide. The silver is used for high current, while the vanadium provides long life and high voltage.

Takeuchi, who earned her bachelor’s degree from the University of Pennsylvania and her doctorate from Ohio State University, has received over 150 patents. The daughter of Latvian emigrants, she received the presidential level National Medal of Technology and Innovation from Barack Obama and has been inducted into the National Inventors Hall of Fame.

Takeuchi continues to push the envelope in her energy research. “We are now involved in thinking about larger scale batteries for cars and ultimately for the grid,” she wrote in an email. “Further, we have demonstrated methods that allow battery components to be regenerated to extend their use. This could potentially minimize batteries going into land fills in the future.”

Takeuchi is one of a growing field of scientists who are using the high-tech capabilities of the National Synchrotron Light Source II at BNL, which allows her to see inside batteries as they are working.

“We recently published a paper where we were able to detect the onset of parasitic reactions,” she suggested, which is “an important question for battery lifetime.”

In the big picture, the scientist said she is balancing between power and energy content in her battery research.

“Usually, when cells need to deliver high power, the energy content goes down,” she said. “The goal is to have high energy and high power simultaneously.”

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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.”

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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.”

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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.

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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.”

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