Power of 3

Above, R.C. Murphy Junior High students Gregory Garra and Gianna Raftery with Catherine Markham in Dawn Nachtigall’s seventh-grade science class last year. Photo from Three Village school district

By Daniel Dunaief

A recent study of 57 species around the world, published in the journal Science, showed that mammals moved distances two to three times shorter in human-modified landscapes.

Catherine Markham, an assistant professor in the Department of Anthropology at Stony Brook University, contributed to this research, adding information about the ranges for baboons in the Amboseli Baboon Research Project in Kenya.

Marlee Tucker, an ecologist at the Senckenberg Nature Research Society based in Frankfurt, Germany, led the effort, which involved working with 114 other scientists who are studying mammals around the world. Tucker “brought together all these research groups on a scale and scope that had not been undertaken before,” Markham said. “She evaluated in an unprecedented way what the implications of human expansion and development are for wildlife movement.”

According to Tucker, a reduction in animal movement could have ecological implications. “It is likely that ecosystem functions such as nutrients and seed dispersal will be altered,” she explained in an email. “However, whether these impacts are negative, positive or neutral requires further research.”

Tucker suggested that it is “important to maintain landscape connectivity so that animals can move freely,” which could include the creation of corridors that link natural landscapes.

While the study made it clear in a comprehensive way that mammals tend to move less when humans interact with them, it didn’t offer specific indications about the causes of that reduction. Some of that, scientists say, could come from fear, as mammals may avoid humans. Alternatively, some mammals might find a new and concentrated food source at garbage dumps and elsewhere that would reduce the need to travel.

Susan Alberts, a professor of biology at Duke University and a collaborator with Markham on baboon research, said that the “take home message” is that “this is a pervasive phenomenon and occurs on a large scale in the mammalian world.”

Markham has been studying baboons in Kenya at the Amboseli site since 2004. When Tucker reached out to her to see if she could contribute to this work, Markham saw an opportunity to collaborate using information she was already gathering.

Above, baboons with a radio collar in the Amboseli National Park in Kenya. Photo by Catherine Markham

As it turns out, baboons in the research project in Kenya live in what Markham describes as a “relatively pristine area” so they did not see “over the time period an increase in the human footprint index.”

Markham shared information about 22 baboons for about 900 days as a part of this research. Tucker’s overarching conclusion included areas where people weren’t encroaching on a mammal’s range. “When she compared the movement of animals living in relatively pristine environments — like the baboons in Amboseli — to the movement of animals living in areas of higher human encroachment, that lead to exciting conclusions,” Markham said. Tucker indicated that future research should focus on exploring the underlying mechanism of the reduction in movement.

In the meantime, Markham is continuing her studies on baboons, exploring the energetic consequences of group size. Larger groups tend to beat out smaller groups when they are competing for food and water in a particular habitat. At the same time, however, those larger groups have stress levels caused by group competition, as one baboon might find the constant proximity and rivalry with another baboon stressful. Baboon group sizes range from a low of around 20 to a high of about 100. Markham is exploring the tension within and between groups.

Over the past few years, Markham, who has been studying this competitive dynamic extensively, has used noninvasive techniques, such as gathering fecal samples, to look for levels of thyroid hormones, which can indicate an animal’s energetic condition.

Alberts explained that Markham was an important contributor to the work at Amboseli, adding that Markham “asks questions at the group level that the rest of us don’t.”

Within the community, Markham has been involved in recent efforts to inspire middle school students at R.C. Murphy Junior High school in Stony Brook to enjoy and appreciate science, working closely with science teacher Dawn Nachtigall, who has been at Murphy for 20 years.

In her second year at Murphy, Markham visits seventh-grade classes several times, discussing her work and explaining how to analyze images from camera traps set up in Kenya and at Sweetbriar Nature Center in Smithtown.

The students receive about 30 photos per pair, Nachtigall explained. Based on the pictures, the students have had to generate questions, which have included whether young deer spend more time with male or female parents, or whether hyenas come out more on full or new moons.

According to Nachtigall, Markham “has such a friendly veneer and an approachable affect” that she readily engages with the students. “She has this wonderful demeanor. She’s soft-spoken, but strong.”

Students in her class appreciate the opportunity to interact with a Stony Brook researcher. “By the end of the period, they are glad to have met her,” Nachtigall added. “Some of them want to become her.”

At the same time, Nachtigall and the other science teachers appreciate the opportunity to hear more from local scientists.

“We live vicariously through her,” Nachtigall said. “It really ignites our own passion for science. Seeing the real-world science for science teachers is just as exciting as it is for students.” Markham is working to post materials online so that teachers and parents can access the information.

A native of Rockville, Maryland, Markham, who joined Stony Brook in 2014, resides in St. James. When she was young, Markham enjoyed the opportunity to join class events in kayaks along the Potomac River. She occasionally saw beaver and bald eagles. Indeed, along the way toward working with baboons, she has also conducted research on bald eagles, monitoring their nests with remote cameras.

As for her work on the Science article, Markham said she is pleased that this kind of collaborative research can provide broad ranging insight to address questions that extend beyond the realm of any one lab or species.

Daniel Mockler in his office at Stony Brook University. Photo from SBU

By Daniel Dunaief

At first, people didn’t believe it. Now, it seems, they are eager to learn more.

Working with a talented team that included postdoctoral researchers, doctoral students and doctors, Kenneth Shroyer, the chairman of the Department of Pathology at Stony Brook University, noticed something odd about a protein that scientists thought played a supporting role, but that, as it turns out, may be much more of a villain in the cancer story.

Known as keratin 17, this protein was thought to act as a tent pole, providing structural support. That, however, isn’t the only thing it can do. The co-director of Shroyer’s lab, Luisa Escobar-Hoyos, found that this protein was prevalent in some types of cancers. What’s more, the protein seemed to be in higher concentration in a more aggressive form of the disease.

Now, working with Long Island native Daniel Mockler, a clinical assistant professor in the Department of Pathology, Shroyer and his team discovered that the presence of this particular protein has prognostic value for endocervical glandular neoplasia, suggesting the likely course of the disease.

Published in the American Journal of Clinical Pathology, the article by Mockler and his team in the Sept. 1, 2017, issue attracted the attention of pathologists around the world. It ranked as the third highest read article in the final month of 2017, according to Medscape. It was behind two other papers that were review articles, which made it the most read primary research report in pathology in December.

The response “did exceed my expectations,” Mockler stated in an email. “I would have thought [Shroyer’s earlier] paper showing that k17 can function in gene regulation would have been more popular. But I guess this [new paper] illustrates that topics that have a possible direct impact on practicing surgical pathologists will draw a lot of attention.”

To be sure, while the recent study is an early indication of the potential predictive value of this protein, there may be some mitigating factors that could affect its clinical applicability.

“It’s premature to know what the clinical utility of this marker will be,” Shroyer said. “To determine that would require a large-scale prospective clinical trial” that would involve other patient populations and other laboratories.

Still, depending on the outcome of research currently underway in Shroyer’s lab, the protein may offer a way of determining the necessary therapy for patients with the same diagnosis.

Doctors don’t want to give patients with milder version of the disease high levels of chemotherapy, which would cause uncomfortable side effects. At the same time, they want to be as aggressive as possible in treating patients whose cancers are likely a more significant threat.

“The goal of having an excellent prognostic biomarker … is to avoid over and under treatment of patients,” suggested Mockler, who is also an attending pathologist at SBU and Stony Brook Southampton.

Shroyer was delighted with the efforts of the team that put together this well-read research. “As is true of all our clinical faculty, I want to give them every opportunity to take advantage of their ability to collaborate with research faculty in our department and throughout the cancer center and the school of medicine to advance their scholarly careers and academic productivity,” he said.

Mockler’s success and the visibility of this paper is “an excellent example of how someone with a busy clinical practice can also have a major impact on translational research,” Shroyer added.

Mockler appreciated the support and work of Escobar-Hoyos, who had conducted her doctoral research in Shroyer’s lab. She has “been the main driving force, along with [Shroyer] in the initial discovery of k17 including its prognostic implications as well as its possible function in regulating gene expression,” he said.

Mockler said he spends about 80 percent of his time on patient care, with the remaining efforts divided between research and academic pursuits. His first priority is providing “excellent patient care.”

Working with Shroyer and Escobar-Hoyos, Mockler explained that they have started looking at k17 in organ systems including the esophagus, pancreas and bladder. “We are currently looking at k17 from a diagnostic point of view in regards to bladder cancer,” he said. “Discoveries that impact the daily signout of surgical pathologists by allowing us to make better and more consistent diagnoses interests me very much.”

A resident of Kings Park, Mockler, who grew up in Hicksville, lives with his fiancée Danielle Kurkowski, who is a medical technologist of flow cytometry research and development at ICON Central Laboratories in Farmingdale.

Daniel Mockler on a recent snowboarding trip to Aspen. Photo from Daniel Mockler

Outside of his work in medicine, Mockler is an avid snowboard enthusiast. He tries to get in as many trips as possible during the winter, including a vacation a few weeks ago to the Austrian Alps. A more typical trip, however, is to western mountains or to Vermont, including Killington, Okemo and Stratton.

“To blow off steam and relax, nothing is better than being on a snow-covered mountain,” he said.

Mockler is pleased with the developments in the department. He has seen the “research goals of the department change quite significantly,” adding that Shroyer has “done a tremendous amount of recruiting.”

Mockler suggests to residents that it’s “good to get involved. I always tell them that [Shroyer] has a pretty active research lab and he likes it when residents get involved.”

As for his work on k17, Mockler is pleased that he’s been able to contribute to the ongoing efforts. Shroyer “has been doing this a while and I have seen the excitement and energy he has put into k17,” he explained, “so I know that we are onto something big.”

And so, apparently, do readers of pathology journals.

Matthew Lerner, far right, with his lab group at Stony Brook University. Photo from Matthew Lerner

By Daniel Dunaief

An actor draws in members of an audience, encouraging them to understand, appreciate and perhaps even become sympathetic to a world created on a stage. The process of creating scenes for the actor, however, can also change his or her world off the stage.

A team of scientists from Vanderbilt University, University of Alabama at Tuscaloosa and Stony Brook University recently received $3 million in funding from the National Institutes of Mental Health for four years to study how participation in a theater production can help people with autism spectrum disorders.

Matthew Lerner. Photo by Graham Chedd from the Alan Alda Center for Communicating Science

“Theater is a venue for learning and gaining skills,” said Matthew Lerner, an assistant professor of psychology, psychiatry and pediatrics at the Department of Psychology at SBU who is leading the Long Island part of a study that will involve about 240 participants from age 10 through 16. “The process of putting on a play with others and being able to successfully produce and perform that has key benefits to learn and practice.”

Called SENSE Theatre (for Social Emotional NeuroScience Endocrinology), the shows were created by the project leader, Blythe Corbett, an associate professor of psychiatry and behavioral sciences and psychology and investigator at Vanderbilt Kennedy Center, who herself performed in stage plays before pursuing her scientific career.

Corbett writes the plays, which have themes she believes are important not only for autism but also for the general public. The topics include acceptance, belonging and diversity and offer a current of core ideas that are “part of having a condition that is unique,” she said. The plays, which typically have about 20 characters, include music and last about 45 minutes.

Tiffany Adams and Jane Goodwin participate in the SENSE Theatre program. Photo by Steve Green, Vanderbilt University

Corbett explained that the experience uses theater as a platform for teaching fundamental areas that could help people with autism spectrum disorders, including reciprocal social communication, flexible thinking and behavior and imagination.

“It also gives [the participants] an opportunity to be exposed to social situations and to engage with others in a safe and supportive environment,” she said. “They can be John today and Henry tomorrow, which allows them to expand their repertoire in a playful, fun way” which, she hopes, might help them assimilate lessons when the program ends.

Corbett has been developing SENSE Theatre for nine years. This specific multisite project will allow her to see how transportable this program is to other locations, where other investigators who have not been involved with this before can employ it with other participants.

The investigators, which include Corbett, Lerner and Susan White at the University of Alabama, will monitor the participants through psychological testing, social interaction and research EEG, or electroencephalography. This is a noninvasive way of monitoring electrical activity in the brain that involves placing electrodes on or below the scalp. The EEG testing takes about 45 minutes.

Participation is free, although members, who go through a screening process, need to contribute to the research program by completing the evaluations.

The theater program has a control study, calling Tackling Teenage Training, in which participants will “address some of the challenges of being a teen,” which include dating and puberty, knowing how to know if somebody likes or doesn’t like you and how to express desires or interests appropriately, Lerner said.

Savannah Bradley participates in the SENSE Theatre program. Photo from Steve Green , Vanderbilt University

Corbett chose to work with Lerner because of considerable overlap in their interests in using performance to provide clinical help for people with autism spectrum disorders. Lerner “has a very strong interest in theater and is able to understand the core approach” to the training and shows as a form of intervention. He is an “engaging, charismatic individual who is extremely hard-working” and is a “really good choice in terms of harnessing his energy and intelligence.”

Indeed, Lerner and Karen Levine, a licensed psychologist and the co-author of “Treatment Planning for Children with Autism Spectrum Disorders,” developed a model in 2004 for youths with disabilities to work on social skills called Spotlight, which utilized techniques of theater games and dramatic training. Spotlight is a program of Northeast Arc, a human services organization founded in 1954 and based in Massachusetts.

The Spotlight efforts started with nine students and has expanded to include hundreds of families each year.

In early high school, Lerner met someone who would change his life. He was having dinner with the family of a friend of his younger sister’s when he noticed a boy, Ben, playing on his own in another room. Lerner asked if he could play with Ben, who was 2 at the time and was running a car back and forth across the top of a toy playhouse.

Lerner mirrored what Ben did. “He looked at me curiously and kept doing what he was doing,” Lerner recalled. “I followed him around for over two hours.”

A scene from a performance by SENSE Theatre. Photo by Steve Green, Vanderbilt University

Up to that point in his life, Lerner thought the experience with Ben was “the most fascinating two hours of my life.” He had made a connection in which he “loved the joy and challenge of trying to meet him where he was, rather than behave in a way that was consistent with what the world expected.”

Lerner studied philosophy and music at Wesleyan University. After earning his doctorate at the University of Virginia, where his dissertation explored why youths with autism experience social problems, Lerner worked at the University of Chicago and then moved to SBU in 2013.

A native of Swampscott, Massachusetts, Lerner lives in Port Jefferson with his wife Chelsea Finn, a pediatric nurse practitioner in the Stony Brook Hospital Emergency Room and a nurse practitioner at SV Pediatrics in Patchogue. The couple has a 4-year-old son Everett and a 6-month-old son Sawyer.

Lerner is looking for people who would like to participate in the study. They can reach out to him by phone at 631-632-7857 or by email at lernerlab@stonybrook.edu. The first set of students will begin working in the SENSE Theatre program this spring and summer.

Corbett said the participants aren’t the only ones who benefit from the program.

“The overwhelming sentiment from those who come to see the performance is that it changes their perception of what it means to have autism,” Corbett said. After the show, some of the audience members “ask who are the children with autism.”

Parents of the actors are pleasantly surprised by the things their children are able to do, which exceed their expectations. “In one of our previous studies, parents reported that their stress went down” during the program, she said, “which appeared to be in response to the child participating in intervention.”

From left, Deyu Lu (sitting), Anatoly Frenkel (standing), Yuwei Lin and Janis Timoshenko. Photo from BNL

By Daniel Dunaief

What changes and how it changes from moment to moment can be the focus of curiosity — or survival. A zebra in Africa needs to detect subtle shifts in the environment, forcing it to focus on the possibility of a nearby predator like a lion.

Similarly, scientists are eager to understand, on an incredibly small scale, the way important participants in chemical processes change as they create products, remove pollutants from the air or engines or participate in reactions that make electronic equipment better or more efficient.

Throughout a process, a catalyst can alter its shape, sometimes leading to a desired product and other times resulting in an unwanted dead end. Understanding the structural forks in the road during these interactions can enable researchers to create conditions that favor specific structural configurations that facilitate particular products.

First, however, scientists need to see how catalysts involved in these reactions change.

That’s where Anatoly Frenkel, a professor at Stony Brook University’s Department of Materials Science and Chemical Engineering with a joint appointment in Brookhaven National Laboratory’s Chemistry Division, and Janis Timosheko, a postdoctoral researcher in Frenkel’s lab, come in.

Working with Deyu Lu at the Center for Functional Nanomaterials and Yuwei Lin and Shinjae Yoo, both from BNL”s Computational Science Initiative, Timoshenko leads a novel effort to use machine learning to observe subtle structural clues about catalysts.

“It will be possible in the future to monitor in real time the evolution of the catalyst in reaction conditions,” Frenkel said. “We hope to implement this concept of reaction on demand.”

According to Frenkel, beamline scientist Klaus Attenkofer at BNL and Lu are planning a project to monitor the evolution of catalysts in reaction conditions using this method.

By recognizing the specific structural changes that favor desirable reactions, Frenkel said researchers could direct the evolution of a process on demand.

“I am particularly intrigued by a new opportunity to control the selectivity (or stability) of the existing catalyst by tuning its structure or shape up to enhance formation of a desired product,” he explained in an email.

The neural network the team has created links the structure and the spectrum that characterizes the structure. On their own, researchers couldn’t find a structure through the spectrum without the help of highly trained computers.

Through machine learning, X-rays with relatively lower energies can provide information about the structure of nanoparticles under greater heat and pressure, which would typically cause distortions for X-rays that use higher energy, Timoshenko said.

The contribution and experience of Lin, Yoo and Lu was “crucial” for the development of the overall idea of the method and fine tuning its details, Timoshenko said. The teaching part was a collective effort that involved Timoshenko and Frenkel.

Frenkel credits Timoshenko for uniting the diverse fields of machine learning and nanomaterials science to make this tool a reality. For several months, when the groups got together for bi-weekly meetings, they “couldn’t find common ground.” At some point, however, Frenkel said Timoshenko “got it, implemented it and it worked.”

The scientists used hundreds of structure models. For these, they calculated hundreds of thousands of X-ray absorption spectra, as each atom had its own spectrum, which could combine in different ways, Timoshenko suggested.

They back-checked this approach by testing nanoparticles where the structure was already known through conventional analysis of X-ray absorption spectra and from electron microscopy studies, Timoshenko said.

The ultimate goal, he said, is to understand the relationship between the structure of a material and its useful properties. The new method, combined with other approaches, can provide an understanding of the structure.

Timoshenko said additional data, including information about the catalytic activity of particles with different structures and the results of theoretical modeling of chemical processes, would be necessary to take the next steps. “It is quite possible that some other machine learning methods can help us to make sense of these new pieces of information as well,” he said.

According to Frenkel, Timoshenko, who transferred from Yeshiva University to Stony Brook University in 2016 with Frenkel, has had a remarkably productive three years as a postdoctoral researcher. His time at SBU will end by the summer, when he seeks another position.

A native of Latvia, Timoshenko is married to Edite Paule, who works in a child care center. The scientist is exploring various options after his time at Stony Brook concludes, which could include a move to Europe.

A resident of Rocky Point during his postdoctoral research, Timoshenko described Long Island as “extremely beautiful” with a green landscape and the nearby ocean. He also appreciated the opportunity to travel to New York City to see Broadway shows. His favorite, which he saw last year, is “Miss Saigon.”

Timoshenko has dedicated his career to using data analysis approaches to understanding real life problems. Machine learning is “yet another approach” and he would like to see if this work “will be useful” for someone conducting additional experiments, he said.

At some point, Timoshenko would also like to delve into developing novel materials that might have an application in industry. The paper he published with Frenkel and others focused only on the studies of relatively simple monometallic particles. He is working on the development of that method to analyze more complex systems.

This work, he suggested, is one of the first applications of machine learning methods for the interpretation of experimental data, not just in the field of X-ray absorption spectroscopy. “Machine learning, data science and artificial intelligence are very hot and rapidly developing fields, whose potential in experimental research we have just started to explore.”

 

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.

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.”

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.”

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.”

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.”

From left, Yuxin Xia, Luke Papazian, Manuela Corcho, Johnny Donza and their thesis advisor Harold Walker. Photo from Johnny Donza

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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