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Power of 3

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From left, Brenna Henn and Meng Lin at a conference last year in New Orleans. Photo from Meng Lin

By Daniel Dunaief

The story of the genetics of skin pigmentation in humans may have even more layers than the skin itself, depending on how close people live to the equator. The conventional wisdom for skin pigmentation is that it is a relatively simple trait, with a small number of genes accounting for almost half of the variety of skin tones.

That, however, isn’t always the case. Pigmentation genetics likely becomes more complex in populations near the equator or with greater variation in pigmentation, like with the Khoisan living in southern Africa.

Above, Brenna Henn, right, with an elder in the Khomani San community who gave her a book on the language formerly spoken in the southern Kalahari Desert. Photo from Brenna Henn

“As you move further toward the equator, the distributions are wide,” Brenna Henn, an assistant professor in the Department of Ecology and Evolution at Stony Brook University, said about the results she, along with collaborators from her lab and from Stanford University, recently published in the journal Cell.

Exploring the genetic determination of skin can serve as a model to understand the broad implications for various genetic variations for different populations as they confront a range of health challenges.

Henn has also worked with tuberculosis studies in South Africa. About one in three people in the world has a latent tuberculosis infection. Researchers have conducted studies to see which genes might be responsible for the different reactions to this disease. Tuberculosis susceptibility studies indicate that different genes may be responsible for infection in different populations, in areas including Russia, West Africa and South Africa.

According to Henn, scientists need to study and understand the disease in different populations to identify, through gene interactions, who will benefit from specific treatments in a vaccination campaign.

When Henn, who is a native of California, started the pigmentation study seven years ago when she was a graduate student at Stanford University, she had considerably different expectations. “When I was a post doc at Stanford, I expected the project to be quick because the genetics of pigmentation in Europeans was relatively well understood,” she explained in an email. When she started analyzing the results, she found that her hypothesis “was not true at all. There are so many different things involved.”

Calling this analysis the “tip of the iceberg,” Henn said she discovered many new genes beyond the ones scientists already knew contributed to skin pigmentation. She estimates that there are 50 if not more genetic sequences involved in skin pigmentation near the equator.

The range of skin pigmentation in South African populations reflected this increased genetic blueprint, with people in these areas demonstrating about twice the variation as people might encounter in a western European population.

These studies require the analysis of considerable data, through a field called bioinformatics, in which researchers analyze and process information through programs that search for patterns. “There’s a huge computational component” to this work, Henn said. “We don’t know where the genes are. We have to sample the entire genome” for as many as 500 people. “This blows up into a computational problem.”

Above, from left, Meng Lin and Brenna Henn at Lin’s graduation ceremony where she earned her PhD. Photo from Brenna Henn

Meng Lin, who worked in Henn’s lab for four and a half years and recently earned her doctorate, performs just such analyses. “We were hoping we’d be able to find some signals that had never been found before, to demonstrate the difference” in the genetic architecture, said Lin, who is now applying for postdoctoral research positions. “Given the prior studies on skin pigmentation traits, the complexity of the genetic architecture we found out was unexpected.”

People near the equator would likely need to have pigmentation that balanced between producing vitamin D from sunlight with protecting their skin from too much exposure to ultraviolet light. In areas such as in Africa, the ultraviolet light can be so strong that “the primary selection factor would be to avoid the photo damage from the strong UV, which favors melanin enriched dark skin pigmentation for photo protection,” Lin explained in an email.

Generally, people further from the equator, such as Scandinavian populations, have lighter skin because they need to process the limited vitamin D they can get, particularly during the darker months. That, however, isn’t the case for the Inuit people, who have darker skin in an area that gets limited sunlight. “Anyone who lives there should be under pressure for light skin,” Lin said. The Inuit, however, are darker skinned, which might be because their diet includes fish and fish oil, which is a rich source of vitamin D. “That would relax the selection force on lighter skin color,” she said.

With people able to travel and live in a wide range of regions across the Earth, selection pressures might be harder to decipher in the modern world. “Travel across continents is a recent” phenomenon, Lin said. The history of such travel freedom is “way too short for changing the genetic components.” Selection pressure occurs over tens of thousands of years, she added.

Diversity and the intake of vitamin D interact closely with each other. They can have impacts on the balance point. Using vitamin supplements could relax the selection on lighter skin, so the balance might shift to a darker population, Lin explained. Other modern lifestyles, such as wearing clothes, staying indoors and consuming vitamin D could complicate this and relax the strength of selection in the future, she added.

A native of China, Lin lives in Port Jefferson Station and enjoys applying math and computer skills to biology. “It’s great fun to solve the questions we have by developing and applying computational methods to existing data,” she said.

After five years at Stony Brook, Henn is transitioning to a position at the University of California at Davis, where she hopes to continue this ongoing work. “We want to follow up on how quickly these selective events occur,” Henn said. She’d like to discover how long it takes for the genetic average of the population to shift.

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Yali Xu and Christopher Vakoc at the 2013 Don Monti Memorial Research Foundation’s Anniversary Ball. Photo from Yali Xu

By Daniel Dunaief

It’s like a top scorer for another team that the greatest minds can’t seem to stop. Whatever they throw at it, it seems to slip by, collecting the kinds of points that can eventually lead to a life-threatening loss. The scorer is a transcription factor called MYB, and the points it collects can, and often do, lead to breast and colon cancer and leukemia.

Researchers have known for over 30 years that stopping MYB could help with cancer treatment. Unlike other possible targets, however, MYB didn’t seem to have the kind of structural weakness that pharmaceutical companies seek, where developing a small molecule could prevent the cancer signals MYB delivered. Some researchers have decided that drugs won’t stop this high-profile cancer target.

Cold Spring Harbor Laboratory Associate Professor Christopher Vakoc and his graduate research assistant Yali Xu, however, have figured out a way around this seemingly intractable problem. The CSHL scientists recently published their results in the journal Cancer Cell.

MYB binds at a small nub to a large and important coactivation protein called TFIID (which is pronounced TF-two-D). This protein is involved in numerous life functions and, without it, organisms couldn’t survive. Vakoc and Xu found that they could use a small peptide decoy to trick MYB into believing it had attached to this protein when, it reality, it hit the equivalent of a molecular dead end.

In a mouse model of acute myeloid leukemia, this peptide caused leukemias to shrink in size by about 80 percent. “What we’ve discovered is head and shoulders above anything we’ve come across before,” Vakoc said.

As with many scientific discoveries, researchers have to clear numerous hurdles between this conceptual discovery and any potential new cancer therapy. “This is not a medicine a person can take,” Vakoc said.

Indeed, scientists and pharmaceutical companies would need to study what leukemia cells escaped this type of treatment to understand how a cancer might rebound or become resistant after an initial treatment. “Our goal is to develop something with longer lasting effects” that doesn’t become ineffective after three to six months, Vakov said. He described understanding the way a disease reacts to a treatment as an “arms race.” Nature inevitably “finds a way to outsmart our decoy. We’d like to know how [it] does it. We’re always trying to study both sides and trying to anticipate” the next steps.

Down the road, Vakoc could foresee researchers and, ultimately, physicians using this kind of approach in combination with other drugs or therapies, the way doctors now provide patients who have the HIV infection with a cocktail of drugs. Conceptually, however, Vakoc is thrilled that this work “highlights what’s possible.”

One of the most encouraging elements of this approach, Vakoc said, is that it combats MYB without harming organ systems. When the researchers gave the treatment to rodents, the mice were “running around, eating and gaining weight.” Their body tissues appeared normal, and they didn’t demonstrate the same sensitivity that is a common byproduct of chemotherapy treatment, such as losing any hair or having problems in their gut.

An important step in this study, Vakoc said, was to understand the basics of how MYB and TFIID found each other. That, Xu said, was one of the first steps in her graduate work, which took about five years to complete.

In Vakoc’s lab, which includes 13 other researchers, he described how scientists make thousands of perturbations to cancer and normal cells, while they are hunting for cancer-specific targets. By using this screening technique, Vakoc and his team can stress test how cancer cells and normal cells react when they are deprived of certain proteins or genes.

“This began as a screen,” he said. “We took leukemia and normal blood cells and did a precise comparison of the perturbation.” They searched for what had the most specific toxicity and, to their surprise, found that interfering with the binding between MYB and TFIID had the strongest effect. “Once we understood what this nub was doing, we applied all kinds of biochemical assay experiments,” Vakov added.

Ultimately, the peptide they found was a fragment of a larger protein that’s active in the cell. Vakoc credits Xu for her consistent and hard work. “When we started on this hunt, we had no idea where this was headed,” he said. Xu was “relentless” in trying to find the answers. “She pieced it all together. It took a great amount of imagination and intellect to solve this puzzle.”

Vakoc suggested that Xu, who plans to defend her thesis this spring and graduate this summer, has set a great example for the other members of his lab. “I now have 13 other people inspired to outdo her work,” he said. “We know we have a new standard.”

Xu is grateful for the support she has received from Vakoc and appreciates the journey from her arrival as a graduate student from China to the verge of her graduation. “It’s very satisfying when you look back and think how things evolved from the beginning to the end” of her graduate work, said Xu, who lives near Huntington Village and enjoys the chance to visit local restaurants and sample coffee and ice cream when she isn’t conducting research toward her doctorate.

The scientific effort, which was published recently, has attracted the attention of others, particularly those who are studying MYB. Vakoc recently received an email from members of a foundation that is funding research on a solid tumor in which scientists believe MYB plays a role. He is writing grants to get more financial support to pursue this concept. Vakoc is encouraged by the opportunity to make progress with a protein that has been “staring [scientists] in the face for three decades.”

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Furie, above sailing on her 26-foot boat that is moored at Manhasset Bay, is navigating the American Journal of Pathology toward new waters. Photo by Richard Furie

By Daniel Dunaief

Martha Furie has a job no other woman has held in the 122-year history of a highly regarded scientific periodical. A professor of pathology and molecular genetics and microbiology at Stony Brook University, Furie is the new editor-in-chief of the American Journal of Pathology, taking over the top editorial job at a journal where she has been a contributor since 1993.

Martha Furie. Photo by SBU

“As a woman, it is certainly gratifying to see an accomplished and capable woman such as Martha being chosen to lead the way,” said Kari Nejak-Bowen, an assistant professor in the Department of Pathology at the University of Pittsburgh, School of Medicine, in an email. “Seeing women such as [Furie] in positions of power and visibility will empower other female scientists to dream that they can accomplish similar goals.”

Richard Mitchell, a senior associate editor at the journal and a professor of pathology and health sciences and technology and vice chair for education at Brigham and Women’s Hospital also applauded the choice. Furie “was probably the very best person we could recruit for the job and is someone who has the energy and vision for leading us into the challenging future,” Mitchell said.

From 1986 through 2014 Furie ran a lab that focused on the study of the body’s immune response to infections from Lyme disease and tularemia, which is cause by a bacterium that is classified as a potential agent of bioterrorism. In 2014, she became the director of the Graduate Program in Genetics at Stony Brook.

Kenneth Shroyer, the chair of the Department of Pathology at SBU, described the periodical Furie starts leading in 2018 as the “top pathology journal.”

As she takes the helm of the journal, Furie plans to navigate the periodical toward more translational research. “The Journal has been very focused on understanding the basic mechanisms of disease,” she said. “Research in all areas is getting much more translational: The bench-to-bedside thinking is where funding agencies are focusing their efforts,” and it’s also where the periodical she now leads is heading.

The tagline for the journal, which Nejak-Bowen said helped pioneer the current understanding of cell death, used to be Cellular and Molecular Biology of Disease. Furie changed that to Discoveries in Basic and Translational Pathobiology.

Shroyer believes the new direction should help the journal compete and redefine its niche for a wider range of readers. While Furie is excited about the opportunity, she acknowledges the increasingly challenging nature of the business. “Scientific publishing is a tough area right now,” she said. “There are fewer people in research because funding has diminished,” while, at the same time, more journals are competing to highlight research discoveries.

She will try to raise the journal’s profile for research scientists. Furie plans on expanding the journal’s social media presence and will do more marketing, while working with expert associate editors and getting them more involved in soliciting submissions. She also plans to make collections of highly cited papers in targeted areas and intends to use these to market the journal to attendees at specialized conferences.

Furie will spend this month contacting each of the associate editors and will solicit suggestions for people who might like to join the publication. She will also seek ideas for the journal. Mitchell suggested that Furie would likely benefit from these interactions. She is a “very good listener and is thoughtful in the questions she asks,” he said. “She is very discerning in assimilating the answers she gets back.” Shroyer expressed confidence in Furie’s leadership, citing a string of accolades and accomplishments in an SBU career that began in 1986.

Above, Furie welcomes students and faculty to the graduate program’s retreat in 2016. Photo by Constance Brukin

Furie was the president of the American Society for Investigative Pathology from the middle of 2011 through the middle of 2012. She was also the recipient of the Robbins Distinguished Educator Award in 2017, which recognizes people whose contributions to education in pathology had an important impact at a regional, national or international level.

Furie and Nejak-Bowen co-organized and co-chaired the ASIP Scientific Sleuthing of Human Disease for High School Teachers and Students in April 2017. With this effort, Furie has already had some success in changing the direction and target audience of an ongoing program. The session, which provides high school teachers with concepts of human disease that they can incorporate into their classroom, now includes high school students.

“This has really revitalized the program, as the students are inquisitive and very engaged with the material,” Nejak-Bowen explained. Furie was “instrumental in encouraging this change in focus, and is passionate about building an improving this session every year.”

The opportunity Furie has as editor-in-chief of the Journal of Pathology “continues her role as a national leader that she’s established,” Shroyer said.

Furie said she benefited from a diverse staff at Stony Brook, that included women like current Professor Emeritus Gail Habicht, when she first arrived. One of the best pieces of advice she received from Habicht was to understand that you can have a family and a successful career.

“You might not be able to do it to the same standard of perfection you did before you had children, but you can have a meaningful career and raise successful children and be happy doing both,” recalled Furie, who has two sons, Jon and Dan, and a 10-month-old grandson Tyler, who lives in Bedford, New York. She is married to Richard Furie, the chief of the Division of Rheumatology at Northwell Health, whom she met in a physics class at Cornell over 45 years ago.

Nejak-Bowen said Furie “leads by example when it comes to work/life balance.” Nejak-Bowen urges women scientists to find a mentor who can offer advice through all stages of a career. She has long considered Furie “a friend, mentor and inspiration.”

Based on Furie’s track record, Shroyer is confident in her continued success and anticipates that the journal will “thrive under her direction.”

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Alexander Krasnitz. Photo by Gina Motis?CSHL

By Daniel Dunaief

Seeing into the future is one of the most challenging, and potentially rewarding, elements of studying cancer. How, scientists and doctors want to know, can they take what evidence they have —through a collection of physical signs and molecular signatures — and determine what will be?

Researchers working on a range of cancers have come up with markers to divide specific types of cancers to suggest the likely course of a disease.

With prostate cancer, the medical community uses a combination of the prostate-specific antigen (PSA), magnetic resonance imagining (MRI) and biopsy results, which are summarized as the Gleason score, to diagnose the likely outcome of the disease. This analysis offers probable courses for developing symptoms.

Cold Spring Harbor Laboratory Professor Michael Wigler and Associate Professor Alexander Krasnitz recently published an article in the journal Cancer Research of a promising study of eight patients that suggests a way of using molecular signatures to determine whether a prostate is likely to contain cells that will threaten a patient’s health or whether the cells are in a quieter phase.

The third most common cancer among Americans, prostate cancer kills an average of 21,000 men each year. Doctors and their patients face difficult decisions after a prostate cancer diagnosis.

“A major challenge is to determine which prostate cancers have aggressive potential and therefore merit treatment,” Herbert Lepor, a professor and Maritin Spatz Chair of Urology at the NYU Langone Medical Center School of Medicine, explained in an email. A collaborator on the study, Lepor provided a clinical perspective and shared patient samples.

A conversation with a doctor after such a diagnosis may include a discussion about how the cancer is not likely to pose an immediate risk to a patient’s life, Krasnitz explained. In that case, doctors do not recommend surgery, which might cause other problems, such as incontinence.

Doctors typically recommend active surveillance to monitor the disease for signs of progression. Some patients, however, make their own decisions, electing to have surgery. The Gleason score, which is typically 3, 4 or 5, can’t provide “meaningful information regarding aggressiveness of the disease,” Lepor explained. “The unique genetic profile of a cancer cell should have infinite more prognostic capability.”

Wigler and Krasnitz, who have been collaborating since Krasnitz arrived at CSHL in 2005, use several hundred single cells from biopsy cores. The research group, which Krasnitz described as a large team including research investigator Joan Alexander and computational science manager Jude Kendall, look for cells with a profile that contains the same irregularities.

“If you take two cells and their irregularities are highly coincident, then perhaps these two cells are sisters or cousins,” Krasnitz explained in an email. “If they are less coincident, then the two cells are more like very distant relatives. We looked for, and sometimes found, multiple cells with many coincident irregularities. This was our evidence for a clonal population.”

By looking at how many biopsy cores contain clonal cells, and then determining how far these clonal cells have spread out through the prostate, the researchers gave these patient samples a score. In this group, these scores, determined before any intervention, closely tracked a detailed analysis after surgery.

“We get a high correlation” between their new score and a more definitive diagnosis that comes after surgery, Krasnitz said. “Our molecular score follows the final verdict from the pathology more closely than the pathological score at diagnosis from the biopsy.”

Wigler, Krasnitz, Lepor and other researchers plan to continue to expand their work at Langone to explore the connection between their score and the course of the disease. Lepor explained that he has been collaborating with Wigler and Krasnitz for five years and suggested this is “an exceptional opportunity since it bridges one of the strongest clinical programs with a strong interest in science (NYU Urology) and a world-class research program interested in clinical care (CSHL).

The research team has submitted a grant to the National Institutes of Health and hopes to expand their studies and provide “compelling evidence” that single-cell genomic mapping “will provide an unmet need defining aggressiveness of prostate cancers,” Lepor said.

While Krasnitz is encouraged by the results so far, he said the team has work ahead of them to turn this kind of analysis into a diagnostic tool physicians can use with their patients.

Realistically, it could take another five years before this score contributes to clinical decision-making, Krasnitz predicted. “You can’t do it overnight,” he cautioned. When this test offers specific signals about the likely outcome for a patient, a researcher would likely need to wait several years as the patient goes on active surveillance to see whether the score has predictive value for the disease in a larger population.

Krasnitz has a sense of urgency to produce such a test because there is “no point in delaying something that potentially looks promising and that one day might well be a part of a clinical practice.”

The work that led to their article took three or four years to complete. The study required technical improvements in the way the researchers processed DNA from single cells. They also had to develop algorithmic improvements that allowed them to use copy number variation to determine clonal structure. The scientists tapped into a wealth of information they gained by taking cells from several locations within the prostate.

Krasnitz was born in Kiev, now part of the Ukraine, and grew up in the former Soviet Union. A resident of Huntington, he lives with his wife Lea, who produces documentaries, including “Maria — The Russian Empress” on Dagmar of Denmark, who was also known as Maria, mother of Nicholas II, the last Romanov czar who was overthrown in 1917. As for his work with Wigler, Krasnitz is excited about the possibilities. “It’s very encouraging,” he said. “We look forward to a continuation of this.”

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Above, Scott Kelly, right, with his twin brother Mark. Photo by Robert Markowitz

By Daniel Dunaief

Dear readers,

Each week, in the Power of Three, Times Beacon Record News Media highlights the efforts of dedicated scientists at Stony Brook University, Cold Spring Harbor Lab and Brookhaven National Lab. This week, we will feature astronaut Scott Kelly, who set an American record for consecutive days in space.

Kelly not only conducted research on flowers and performed space walks while orbiting the Earth, he also became his own living laboratory, taking blood samples to compare to his twin brother Mark. Some day, the pioneering studies from the twins may turn the dream of a trip to Mars and beyond into a reality.

He had a spectacular view for close to a year, watching 16 sunrises and sunsets each day aboard the International Space Station. He even pretended to catch a pass thrown by television host Stephen Colbert from over 249 miles away.

A view of Earth aboard the ISS. Photo by Scott Kelly

Astronaut Scott Kelly set an American record for consecutive days in space, floating from one part of the multinational station to another for 340 days. During that journey, in which Kelly traveled over 143 million miles with cosmonaut Mikhail Kornienko, the New Jersey native conducted numerous experiments, including on himself. NASA plans to use the information gained from Kelly’s mission to design future extended trips into space, including any future journey to Mars.

Kelly, who returned to Earth in March of 2016, recently published a book titled “Endurance: A Year in Space, a Lifetime of Discovery” (Knopf), in which he shared a long journey from underachieving high school student to celebrated astronaut.

“There are things about the experience that are absolutely amazing,” he said, “but, then, at the same time, the things that make everything amazing also make other things more difficult.” For starters, moving from a Soyuz rocket to the space station isn’t as simple as stepping out of a car and opening another door. When the rocket attaches to the station, it can take hours to equalize the pressure. In a film or documentary of life in space, “You can’t show 11 hours of docking or six hours of preparation to go out on a space walk,” Kelly said.

Once aboard, the astronaut, who had lived on the space station on an earlier six-month mission, said he had to adapt to the logistics of meals in space. Gravity doesn’t hold the astronauts on a chair or their food on a plate. For close to a year, he couldn’t relax his body while eating, which meant that he felt like he was standing and balancing during meals.

Scott Kelly and Mark Kelly in 1967. Photo from Scott Kelly

Kelly said the transition from life on Earth to the station, and then back again, requires adjustments. One of the most significant scientific efforts he was a part of originated from a conversation Kelly had with a NASA scientist, asking him what he should say if a reporter asked if NASA was comparing the changes in his body to those of his identical twin brother Mark. The NASA scientist then asked if he and his brother, who is a retired astronaut, would consider participating in such an effort. Thus, the NASA Twins Study was born.

Before his mission, Kelly got several small tattoos on his body, to make sure he was drawing blood from the same place each time. Scientists have spent over a year examining changes in his genes. While more results will be published next year, the work so far shows an uptick in the methylation of Scott’s DNA. That means he potentially had more signals that can turn on or off genes.

Additionally, Scott’s telomeres, which protect the ends of DNA strands, were longer during the same period than those of his Earth-bound twin. Also, Scott returned from space closer to two inches taller than his brother because the discs in Scott’s spinal column weren’t compressed by gravity. That difference didn’t last long, however, as his spine returned to normal after he came back to Earth.

While life aboard the space station included movies like “50 Shades of Grey” in Russian and books like “The Right Stuff” by Thomas Wolfe, which Kelly said inspired him to become an astronaut, it also involved unusual environmental challenges.

Scott Kelly. Photo from NASA

As part of his training, Kelly needed to recognize any of the symptoms of carbon dioxide buildup in his system. His girlfriend Amiko Kauderer provided some necessary observations during one particular conversation. Within seconds of speaking with him, Kauderer told him to stop talking to her and check the carbon dioxide levels. She quickly had diagnosed that the carbon dioxide levels, while not dangerously high, were above Kelly’s comfort level.

Kelly explained that the routine in space doesn’t leave much time for relaxation or down time. “You have one day on the weekend when you’re off,” he said. “You can arrange your workweek such that you’re taking advantage of that. You still have stuff like cleaning the space station and you still have to exercise and organize the living environment.”

Indeed, astronauts need to exercise aboard the station or risk losing bone mass and encountering muscular atrophy during their missions. In addition to stretching his body, Kelly expanded the typical limits of his responsibility for some scientific experiments.

As he chronicled in his book, he was following a protocol for growing zinnias. When the flowers weren’t flourishing, Kelly asked NASA if he could take over the decision-making process, which NASA approved. “The satisfaction came more from the idea that it was an experiment that we were making the decisions on and controlling,” he said.

Typically, he reported what he saw to NASA, and scientists back on Earth came up with a plan that they sent to Kelly. While they required considerable effort, the astronaut also took satisfaction in the three space walks he conducted during his journey. As with the movie “Gravity,” Kelly recognized the danger that orbiting space debris, even small pieces, could pose for the space station and him. “You could get hit with something that would not only put a hole in your visor, but would put a hole in your head,” he said.

Kelly didn’t bother watching out for such objects when he’s outside the station because he’d “never see it coming at you at 17,000 miles an hour.” As for what he could see from space, Kelly watched wildfires in California and Hurricane Patricia, which was a storm off the coast of Oman. In addition to information NASA might take from his mission that could inform decisions about future missions, Kelly hopes people view his experience, and his success, as a model for them.

“There’s a lot of opportunities for redemption in the United States,” Kelly said. “It’s not the preferred or easy path, but it is a path, especially in this country.”

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BeLocal winners from left, Yuxin Xia, Luke Papazian, Manuela Corcho, Johnny Donza and their thesis advisor Harold Walker. File photo

By Daniel Dunaief

Yuxin Xia and Johnny Donza

Johnny Donza wants to use the training he’s received as an engineering undergraduate at Stony Brook University to help people 8,600 miles and another continent away in Madagascar.

The group leader of a senior project, Donza is working with Yuxin Xia, Luke Papazian and Manuela Corcho to design and hopefully help build a bridge that will cross a stream on the outskirts of the village of Mandrivany. People living in that village had been walking across a log that has broken to buy and sell food or get to a hospital.

“I wanted to be involved in something that would make an impact,” said Donza, who is studying civil engineering with a concentration in structural engineering. This project presented an opportunity to help “people on the opposite side of the world. I thought that was pretty cool.”

Donza’s project is one of 15 senior design efforts that arose from a collaboration between Stony Brook and a group called BeLocal. The company sent Stony Brook graduates Acacia Leakey and Leila Esmailzada to collect video footage this summer in Madagascar. They hoped to return with the kind of information about the needs and resources of the people they met.

“These projects create the perfect opportunity for students to manage a real engineering project,” Harold Walker, professor and chair of the Department of Civil Engineering, explained in an email. Walker is Donza’s senior advisor on the project. “The experience the students have with these projects will be invaluable as they start their engineering careers.”

Acacia Leakey, on left

Walker said he initially expected to have one team of four to five students work with BeLocal in Civil Engineering. Instead, 13 students signed up. Walker spoke with Leakey and they decided to divide the students into three teams, each of which is working on different types of bridges. “If the bridge design can be implemented locally in Madagascar, this will improve the safety of river crossings and also provide the community [with] greater access to education and other opportunities,” he continued. “A bridge may seem like a simple thing but it can really be transformative.”

In addition to the bridge project Donza and his teammates are developing, Stony Brook teams are working on projects including rice storage, rat control, rice processing and briquette manufacturing.

Eric Bergerson, one of the three founders of BeLocal along with Mickie and Jeff Nagel of Laurel Hollow, said the group was thrilled with the range and scope of the projects. The response is “overwhelming,” Bergerson said, and “we couldn’t be happier.” Bergerson is the director of research at the social data intelligence company TickerTags.

For their project, Donza’s group is exploring the use of bamboo to create the bridge. “Deforestation in the region is a major problem,” which reduces the ability to find and use hardwood, Donza said. “Bamboo grows rampantly, so there’s plenty of bamboo we can use.”

To gather information about the structural details about this material, Donza and his team are testing bamboo they harvested from the Stony Brook campus. Leakey, who is earning her master’s at SBU after she did a Madagascar senior design project last year, said using bamboo creates a useful supply chain. “It’s such a sustainable resource,” said Leakey, who speaks regularly with Donza and other project managers who are seeking additional information about how to use local resources to meet a demonstrated need in Madagascar.

The Stony Brook team is working to model its structure after the Rainbow Bridge, which is an ancient Chinese bridge. The Rainbow Bridge has a longer span and has a more exaggerated arch than the one Donza and his classmates are designing. The group plans to build a structure that will hold several people at the same time. During monsoon season, the stream below the bridge also floods. The design may need to include nails or bolts, creating a durable, longer-lasting bond between pieces of bamboo.

The team is also waiting to collect information about the soil around the stream, so they know what kind of foundation they can construct. In their design, they are trying to account for a likely increase in the population and future windy conditions.

Donza said he and his team are excited to make a meaningful contribution to life in Madagascar. “We’re not just doing this to graduate,” he said. “We’re doing this because we have a chance to help people. They need this bridge.”

Leila Esmailzada

The BeLocal approach to the collaborations with Stony Brook involves learning what people need by observing and interacting with them, rather than by imposing expectations based on experiences elsewhere. Esmailzada said they spoke with women about various materials because women were the ones using the charcoal and firewood.

At some point, BeLocal may also foster an exchange that allows students from Madagascar to come to Stony Brook to learn from their American counterparts while also sharing first-hand information about what might work in Madagascar. “It’d be great if we could get people to come” to Stony Brook, Bergerson said. “We’re just developing relationships with universities now.”

Leakey said Stony Brook students have shown genuine interest in life in Madagascar and, as a result, have found some surprises. People across various disciplines assume incorrectly that developing nations progress along the same technological path that America did, which leads them to the inaccurate expectation that Madagascar is 100 years behind the United States. When engineering students learned that “people in Madagascar have smartphones” with Twitter and Facebook accounts, “their jaws fall. It’s important to recognize that so you can realize it isn’t a simple story that you’re innovating for and that there is this mixture of technology that’s familiar in a lifestyle that’s unfamiliar.”

Even while these projects are still in the formative stages, with students continuing to gather information and refine their projects, Walker suggested they have already provided value to engineering students. “The students have already learned a great deal,” Walker explained. They appreciate how their classroom skills “can really transform the lives of people across the world.”

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Above, Israel Kleinberg, right, with Mitch Goldberg, president of Ortek Therapeutics

By Daniel Dunaief

What if dentists could see developing cavities earlier? What if, once they discovered these potential problems, they could help their patients protect their teeth and avoid fillings? And, to top it off, what if they could do this without exposing their patients to radiation from X-rays?

The Electronic Cavity Detector

That’s exactly what Israel Kleinberg, a longtime Stony Brook University dental researcher and the founding director of the Division of Translational Oral Biology at SBU, recently developed. Called the electronic cavity detector, this new tool was recently approved by the Food and Drug Administration.

The device monitors mineral loss in enamel of molars and premolars. Powered by a battery, the handheld ECD uses electrical conductance to diagnose and monitor lesions. Tooth enamel does not conduct a signal. A lesion or crack in the enamel, however, will allow the ECD to record an early indication of a developing cavity.

“The ECD can detect lesions that are microscopic and [detect them] much sooner than X-rays,” Kleinberg explained in an email. Other research has shown that “X-rays are not very effective for diagnosing incipient enamel caries [cavities], though the technique is very useful for diagnosing deeper lesions.”

Ortek Therapeutics, a small company based in Roslyn Heights, supported the research to develop the technology over the last 10 years. Ortek is developing plans to commercialize the ECD, which could be available at a neighborhood dentist’s office by the middle of next year.

Mitch Goldberg, the president of Ortek, said the response to a positive reading on the ECD will depend on the dental practitioner. A very low conductance number could suggest a dentist pay further attention to the specific tooth. It might also lead a dentist to suggest improving oral care, brushing better or prescribing a fluoride rinse, among other options.“If the number is higher, the dentist will decide the appropriate treatment option, which could include minimally invasive procedures,” Goldberg said.

Goldberg, whose firm invested over $1 million in the work, is excited about the prospects for the ECD, for which Ortek filed and received a patent and then went through the FDA approval process. “It’s a painless” way to monitor teeth, Goldberg said. “There’s no radiation [involved].”

To be sure, he said the ECD won’t replace X-rays, particularly for teeth that already have a crown or other dental work or that are already known to have cracks or fissures. Still, Goldberg said this device could help monitor back teeth, where tiny lesions would not be causing a patient pain. The examination itself will require a short exam by either a hygienist or a dentist, who can put a probe in the bottom of a groove and gently move it along the tooth.

Any dental professional could be “trained on this in about 15 minutes,” Goldberg said. “They do similar types of work when they are probing and cleaning” teeth. Practitioners would likely understand the approach quickly, he said.

To operate the device, a dentist places a lip hook in the patient’s mouth. The dentist then puts a cotton roll between the tooth and the cheek, then air dries the tooth, Kleinberg explained in an email. The dentist lightly touches the tooth with the ECD probe and testing is completed in seconds.

Israel Kleinberg

Kleinberg, who has been developing this device for 14 years, suggested that the most common potential causes of false readings might be failure to dry the surface and operator error. The researcher developed this product with Stony Brook University Research Assistants Robi Chatterjee and Fred Confessore.

The partnership with Stony Brook has been a “win-win” for Ortek. Indeed, Kleinberg also developed a product called BasicBites. The chewable BasicBites provide a pH environment that supports healthy bacteria in the mouth. At the same time, BasicBites makes it harder for the bacteria that eats sugars and produces acids that wear away minerals on teeth to survive. The product make it tough for the acid-producing bacteria to eat food leftovers stuck between or around teeth.

Kleinberg, who has been with Stony Brook for 44 years, still works full time and shows no signs of slowing down. The researcher is the founding chairman of the Department of Oral Biology and Pathology. He stepped down from that position in 2009. Goldberg said he speaks with Kleinberg several times a week and calls his partner in cavity fighting an “inspiration,” adding that Kleinberg is considered the grandfather of oral biology.

Goldberg said he has a great sense of satisfaction when he goes to a pharmacy. “I take a glance at some of the products on store shelves that came out of Stony Brook and Ortek and it does give me tremendous pride,” he said.

Goldberg said he can’t disclose the market size for the ECD. He added that there are over 100,000 general dentists in the country who treat people of all ages. “There’s a tremendous opportunity for us,” he said, suggesting that dentists could check for any signs of early tooth decay before putting on a sealant.

Taking a similar approach to the BasicBites work, Kleinberg, with support from Ortek, is also researching skin-related technology for fighting MRSA-related infections and body odor. Goldberg said unwelcome bacteria often contribute to unpleasant smells that come off the skin. Ortek is also promoting the growth of healthy bacteria that reduce those scents.

While still in the early stages of development, Kleinberg has “developed a patented cutaneous or skin microbiome technology that promotes the growth of beneficial bacteria while crowding out harmful microbes,” Goldberg said. By exploring the microbiome, Kleinberg can promote the growth of better bacteria in the feet and under the arms.

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Joel Saltz. Photo from SBU

By Daniel Dunaief

In the battle against cancer, doctors and scientists use targeted drugs to treat the disease. They also employ radiation, starve it of the nutrients it might need to grow, block key metabolic pathways in its development and encourage the immune system to attack these genetically misdirected cells that grow out of control. A developing field in this battle includes the use of computers, artificial intelligence and math.

Joel Saltz, the Cherith Chair of Biomedical Informatics at Stony Brook University, recently teamed up with researchers from Emory University and the University of Arkansas and won an $8 million grant from the National Cancer Institute to coordinate radiology and pathology information in the battle against cancer.

“By gathering more information, researchers can understand better what’s happening, what might happen and how best to treat cancer,” Saltz said. The grant will be divided equally among the three institutions over the course of five years. Saltz will be collaborating with Ashish Sharma at Emory and Fred Prior at the University of Arkansas.

Saltz has been working with Sharma for several years, when the two were at Ohio State and then moved together to Emory. This is Saltz’s first major grant with Prior, although the two have also known each other for years and have been working in the same NCI program.

Prior has considerable expertise in radiology, while Saltz is adding his pathology background to the mix. Radiology has used digital imaging for a long time and, until recently, pathology data was collected on glass slides. Saltz is helping bring digital pathology to this effort.

“We had been on panels for many years with NCI saying we need to do this sort of” collaboration, Saltz added, and now the trio is putting that idea to work.

Yusuf Hannun, the director of the Cancer Center at Stony Brook, sees the potential for this type of collaboration. “This is a very important effort that builds on several areas of outstanding strength” at the Cancer Center, the director explained in an email.

Exploring information from digitized radiology and pathology samples will “allow us to understand individual cancers at a much higher level. It should improve accuracy in diagnosis [and offer an] ability to provide better informed prognosis” and individual therapy, Hannun continued.

Researchers on the current grant, which is part of the Information Technology for Cancer Research, plan to expand resources for integrative imaging studies, build on the capacity to acquire high-quality data collections, dedicate resources to support reproducible research and increase community engagement.

Saltz will use the portion of the Stony Brook funds to develop new software integration tools and curation and work with researchers to analyze and understand their patient data. Over time, he will also hire additional staff to build out this expertise. He has collaborated with Kenneth Shroyer, chair of the Department of Pathology at Stony Brook, on pancreatic and ovarian cancer and on breast cancer with pathology professor Patricia Thompson, who is also director of basic science at the Cancer Center. Shroyer “plays an important role” in all his research, Saltz said.

“Digital pathology will supplement that art of surgical pathology with quantitative data, to improve diagnostic accuracy,” Shroyer wrote in an email, which will “inform decisions on how to optimize therapeutic intervention for the treatment of cancer and many other diseases.”

Shroyer interviewed Saltz before Stony Brook hired its first bioinformatics chair. “Based on his research focus, including his pioneering efforts in digital pathology, he clearly stood out as my top choice.”

Saltz and Shroyer have generated maps of patterns for immune cells in tumors. “We and others have shown that these are related to how patients respond to treatment,” Saltz said. He described his work with these scientists as “basic clinical cancer research,” in which he develops and enhances technology to understand various types of cancer.

This particular grant is “more about technology and curation,” Saltz said. “People are developing new algorithms, in artificial intelligence and machine learning.” By making this information available, scientists from around the world who have insights into the specific types of cancer can use it to predict responses to treatment and develop and refine the algorithms that underlie the computer analysis.

Using specific cancers from radiology and pathology studies is akin to sitting in a football stadium and examining a blade of grass from the bleachers, Saltz suggested, borrowing from a phrase he’d heard at a recent panel discussion with Liron Pantanowitz from the Department of Pathology at the University of Pittsburgh Medical Center.

“What we do is we create catalogs of every blade of grass and every worm and weed,” Saltz added. “It’s a huge database problem” in which he is integrating software development.

Hannun, who has been working to help Stony Brook University earn a National Cancer Institute designation, suggested that this bioinformatics work is “a critical component of our plans” and represents an area of exceptional strength.”

Cancer bioinformatics is “one of the main pillars of our research program and it integrates well with our efforts in imaging, metabolomics, improved diagnostics and improved therapeutics,” Hannun explained.

As for his department, Saltz said Stony Brook will have its first biomedical informatics Ph.D. graduate at the end of 2017. Yanhui Liang joined Stony Brook when Assistant Professor Fusheng Wang came to Long Island from Emory. Xin Chen will graduate in May of 2018.

The doctoral program, which launched last year, has five current students and “we’re hoping to get a bigger class this year,” Saltz said. “Informatics involves making techniques for better health care,” Saltz said. People with medical degrees can do fellowship training in clinical informatics.

A resident of Manhasset, Saltz lives with his wife Mary, who is an assistant clinical professor of radiology at Stony Brook University. Over the course of the next five years, Saltz said he believes this grant will continue to allow him and his collaborators to develop tools that will help provide insights into cancer research and, down the road, into personalized cancer treatment.

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Minghua Zhang

By Daniel Dunaief

Minghua Zhang spent a sabbatical year in China trying to improve climate models, which included analyzing errors of current models.

A professor at the School of Marine and Atmospheric Sciences at Stony Brook University, Zhang focused on the Southern Great Plains of the United States. He explored how the current models did not accurately simulate convection, which created a warm and dry bias.

In convection, heat and moisture get carried upward. The models account for summer rainfall but do not calculate the organizational structure of the convective systems, which led them to simulate insufficient precipitation.

By adding in the new information, Zhang predicts in recent research published in the scientific journal, Nature Communications, that the projected warming in the region would be 20 percent less than previously thought. Precipitation, meanwhile, would be about the same as it is today, instead of the drying that was previously anticipated.

“The resolution of the models is not high enough to predict the change of the convection with a high degree of precision,” Zhang explained in an email.

He suggested that using 10 times the specificity of model calculations, he expects a clearer picture of the likely climate by the end of the 21st century. This is like looking through binoculars at a nondescript moving shape in the distance. By adding focal power to the lens, the image can become sharper and clearer.

The climate is a big picture view of trends over the course of many years. That is distinct from weather, which involves day-to-day variations and which meteorologists describe each morning and evening with colorful images of cold and warm fronts on local maps.

“You have many things you can’t see and now you have better binoculars,” he suggested. “This tiny thing in the binoculars can make a bigger impact. What we see is that these [variables] actually matter.”

Zhang suggested that a climate model that better accounts for summer rainfall still includes higher temperatures in this sensitive region. “The warming is going to be there and will be significant,” he said. If carbon dioxide emissions continue at their current rate, the warming will still be about five degrees by the end of the century, he suggested. That, he predicted, will still have a significant impact on agriculture.

Edmund Chang, a professor at the School of Marine and Atmospheric Sciences at Stony Brook who was not involved in this study, said this research addresses “a specific bias of the model that needs to be taken care of.” He added that researchers know that the “models are not perfect” and suggested that the “scientific and climate modeling community is trying to refine and improve” these tools.

Chang agreed that the refinement “doesn’t change the fact that we still project a large increase in the temperatures over the central United States.”

The Southern Great Plains region has some unique elements that make climate predictions challenging. It has considerable organized convection, which increases the occurrence of tornadoes. There’s also a large coupling between the soil moisture and the clouds, which means that whatever happens on the land has feedback for the atmosphere.

Zhang said his research focus is on climate simulation modeling. He knew the models had problems simulating convective events, which is why he started exploring this specific region. “The way the models are constructed, the granules are not small enough,” he said.

Chang expected that this work would “spur more research on trying to understand this mechanism. Model developers will need to try to find out how to improve the physical model.”

Zhang has been working for the last two years with scientists from Tsinghua University in China, which included his time on sabbatical. “When you are on sabbatical, you have more time to really think about problems,” he said.

Chang added that sabbaticals can provide some time to focus on specific scientific questions. During a typical semester that includes administrative responsibilities and teaching, professors “are very busy,” He said. “We really don’t have an extended period of time to focus on one project. The sabbatical gives us a chance to focus.”

Zhang hopes this study “motivates people to think about how to improve their models in describing” other climate systems.

One of the many challenges scientists like Zhang face in developing these climate models is that their computers are still not powerful enough to resolve elements like clouds, which not only dot the landscape and provide shade during the summer but also send the sun’s energy back into space.

The system he’s studying is “chaotic by nature,” which makes accounting for elements that change regularly challenging. He suggested that these studies were akin to the butterfly effect. Scientists have suggested that someone who went back in time and committed a seemingly trivial act, like killing a single butterfly, might return to his familiar time and surroundings to discover profound changes.

While that’s an exaggeration, that’s still the kind of system he said researchers are confronting as they try to account for, and weigh, climate defining factors. That’s why he’s looking for statistical, or probabilistic, predictions that are averaged over time periods.

The United States, China and the European Union are all pursuing more powerful computers for these kinds of applications, Zhang said.

Zhang, who is the editor-in-chief of the Journal of Geophysical Research: Atmospheres, has been involved in an advisory capacity with the United States Department of Energy in developing these models. A

s for this specific effort, Zhang said he was pleased that the paper pointed out a research direction to refine models for climate in this area. “What we see is that these things [including convection] actually matter,” he said. “That’s the main contribution of this paper.”

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From left, BNL Staff Scientist Lihua Zhang, former postdoctoral researcher Vitor Manfrinato and BNL Senior Scientist Aaron Stein. Photo courtesy of BNL

By Daniel Dunaief

It took a village to build this particular village or, more precisely, a pattern so small it could fit thousands of times over on the head of a pin.

Working at Brookhaven National Laboratory’s Center for Functional Nanomaterials, a team of researchers wanted to exceed the boundaries of creating small patterns with finely honed features. The group included Aaron Stein, a senior scientist at CFN, Charles Black, the head of CFN, Vitor Manfrinato, a former postdoctoral researcher at BNL and several other key members of the BNL team. The team added a pattern generator that allowed them to control a microscope to create a pattern that set a record for drawing at the 1-nanometer scale.

Just for reference, the width of a human hair is about 80,000 to 100,000 nanometers. The size of the pattern is a breakthrough as standard tools and processes generally produce patterns on a scale of 10 nanometers. “We were able to push that by a factor of five or 10 below,” Stein said. “When you get to those small size scales, that’s pretty significant.”

In this case, the novelty that enabled this resolution originated with the idea of employing the scanning transmission electron microscope, which isn’t typically used for patterning to create these images. The scanning transmission electron microscope has an extraordinarily high resolution, while the pattern generator allowed them to control the patterns they drew and other aspects of the exposure.

Researchers at CFN are focusing on this spectacularly small world to manipulate properties such as chemical reactivity, electrical conductivity and light interactions. “This new development is exciting because it will allow other researchers to create nanomaterials at previously impossible size scales,” Kevin Yager, a group leader at CFN explained in an email. “There are numerous predictions about how materials should behave differently at a size scale at 1 to 3 nanometers. With this patterning capability, we can finally test some of those hypotheses,” he said.

Stein and the research team were able to create this pattern on a simple polymer, polymethyl methacrylate, or PMMA for short. “It’s surprising to us that you don’t need fancy materials to create these kinds of features,” said Stein. “PMMA is a common polymer. It’s Plexiglas. It’s kind of exciting to do something that is beyond what people have done” up until now.

One of the many possible next steps, now that the researchers have developed this proof of principle, is to apply this technique to a substance that might have commercial use. Taking the same approach with silicon, for example, could lead to innovations in electronics. “We can make them with a high clarity of patterns and sharp corners, which we can’t do with other techniques,” Stein said.

The BNL research team would “like to apply this to real world research,” which could include electronics and transistors, as well as photonics and plasmonics, he added. This project arose out of a doctoral thesis that Manfrinato was conducting. He is one of the many scientists who came to BNL, which isa Department of Energy funded user facility that provides tools to conduct research for scientists from around the world.

Manfrinato was a doctoral student in Professor Karl Berggren’s group at the Massachusetts Institute of Technology. In an email, Manfrinato explained that he was interested in pushing the resolution limits of e-beam lithography. “BNL has state of the art facilities and expert staff, so our collaboration was a great fit, starting in 2011,” he explained.

Other scientists thought it was worthwhile to continue to pursue this effort, encouraging him to “come here and work on this. It’s a home grown project,” Stein said. Manfrinato worked on his doctorate from 2011 to 2015, at which point he became a postdoctoral researcher at BNL. His efforts involved several groups, all within the Center for Functional Nanomaterials at BNL. Stein, Manfrinato and Black worked on the lithography part of the project, while Lihua Zhang and Eric Stach developed the microscopy. Yager helped the team to understand the processes by which they could pattern PMMA at such small scale lengths.

“No one or two of us could have made this happen,” Stein said. “That’s really the joy of working in a place like this: There are [so many] permutations for collaborating.” Indeed, the other scientists involved in this study were Yager; Zhang, a staff scientist in electron microscopy; Stach, the electron microscopy group leader at CFN; and Chang-Yong Nam, who assisted with the pattern transfer.

Manfrinato, who is now a research and development engineer at a startup company in the San Francisco Bay area, explained that this lithographic technique has numerous possible applications. Other researchers could create prototypes of their devices at a level below the 10-nanometer scale at CFN. Manfrinato interacts with the BNL team a few times a month and he has “exciting results to be further analyzed, explored and published,” he wrote in an email.

Stein said BNL would like to offer this patterning device for other users who come to BNL. Ultimately, researchers use materials at this scale to find properties that may vary when the materials are larger. Sometimes, the properties such as color, chemical reactivity, electrical conductivity and light interactions change enough to create opportunities for new products, innovations or more efficient designs.

A resident of Huntington, Stein and his wife Sasha Abraham, who works in the planning department for the Town of Huntington, have a 15-year-old daughter Lily and a 13-year-old son Henry.

As for his work, Stein said he’s interested in continuing to push the limits of understanding various properties of nanomaterials. “My career has been using the e-beam lithography to make all sorts of structures,” he said. “We’re in a regime where people have not been there before. Finding the bottom is very interesting. Figuring out the limits of this technique is, in and of itself” an incredible opportunity.

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