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Power of 3

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Tobias Janowitz with research technician Ya Gao at Cold Spring Harbor Lab Photo by ©Gina Motisi, 2019/CSHL

By Daniel Dunaief

It’s a low-tech setting with high stakes. Scientists present their findings, often without slides and pictures, to future colleagues and collaborators in a chalk talk, hoping faculty at other institutions see the potential benefit of offering them an employment opportunity.

For Tobias Janowitz, this discussion convinced him that Cold Spring Harbor Laboratory was worth uprooting his wife and three young children from across the Atlantic Ocean to join.

Chalk talks in most places encourage people to “defend their thinking. Here, it was completely different. They moved on from my chalk talk quickly,” said Janowitz in a recent interview.

Research technician Ya Gao and Tobias Janowitz at Cold Spring Harbor Lab. Photo by ©Gina Motisi, 2019/CSHL

Janowitz recalled how CSHL CEO Bruce Stillman asked him “what else will you do that’s important and high risk. He moved me on from that discussion within five minutes and essentially skipped a step I’d usually spend at another institution. It’s a very special place.”

Janowitz, who earned a medical degree and a doctorate from the University of Cambridge, came to the lab to work in a field where he’s distinguished himself with cancer research that points to the role of a glycoprotein called interleukin 6, or IL-6, in a specific step in the progression of the disease, and as a medical oncologist. He will work as a clinician scientist, dedicated to research and discovery and advancing clinical care, rather than delivering standard care.

As CSHL continues to develop its ongoing relationship with Northwell Health, Janowitz said he expects to be “one of the intellectual bridges between the two institutions.”

In his research, the scientist specializes in understanding the reciprocal interaction between a tumor and the body. Rather than focusing on one type of cancer, he explores the insidious steps that affect an organ or system and then wants to understand the progression of signals and interactions that lead to conditions like cachexia, in which a person with cancer loses weight and his or her appetite declines, depriving the body of necessary nutrition.

CSHL Cancer Center Director David Tuveson appreciates Janowitz’s approach to cancer.

“Few scientists are ready to embrace the macro scale of cancer, the multiple organ systems and body functions which are impaired,” Tuveson said. Janowitz is “trying to understand the essential details [of cachexia and other cancer conditions] so he can interrupt parts of it and give patients a better chance to go on clinical trials that would fight their cancer cells.”

A successful and driven scientist and medical doctor, Janowitz “is very talented and could be anywhere,” Tuveson said, and was pleased his new colleague decided to join CSHL.

Janowitz suggested that the combination of weight loss and loss of appetite in advancing cancer is “paradoxical. Why would you not be ravenously hungry if you’re losing weight? What is going on that drives this biologically seemingly paradoxical phenomenon? Is it reversible or modifiable?”

At this point, his research has shown that tumors can reprogram the host metabolism in a way that it “profoundly affects immunity and can affect therapy.” Reversing cachexia may require an anti-IL-6 treatment, with nutritional support.

As he looks for clinical cases that could reveal the role of this protein in cachexia, Janowitz has seen that patients with IL-6-producing tumors may have a worse outcome, a finding he is now seeking to validate.

At this point, treatment for other conditions with anti-IL-6 drugs has produced few side effects, although patients with advanced cancer haven’t received such treatment. Researchers know how to dose antibodies to IL-6 in the human body and treatment intervals would last for a few weeks.

Scientists have long thought of cancer as being like a wound that doesn’t heal. IL-6 is important in infections and inflammation.

Ultimately, Janowitz hopes to extend his research findings to other diseases and conditions. To do that, he would need to take small steps with one disease before expanding an effective approach to other conditions. “Are disease processes enacting parts of the biological response that are interchangeable?” he asked. “I think that’s the case.”

Eventually, Janowitz hopes to engage in patient care, but he first needs to obtain a license to practice medicine in the United States. He hopes to take the steps to achieve certification in the next year.

He plans to gather samples from patients on Long Island to study cancer and its metabolic consequences, including cachexia.

Several years down the road, the scientist hopes the collaborations he has with neuroscientists can reveal basic properties of cancer.

Tuveson believes Janowitz has “the potential of having a big impact individually as well as on everyone around him,” at Cold Spring Harbor Laboratory. “We are lucky to recruit him and want him to succeed and solve vexing problems so patients get better.”

Janowitz lives in Cold Spring Harbor Laboratory housing with his wife Clary and their three children, Viola, 6, Arthur, 4, and Albert, 2.

Clary is a radiation oncologist who hopes to start working soon at Northwell Health.

The Janowitz family has found Long Island “very welcoming” and appreciates the area’s “openness and willingness to support people who have come here,” he said. The family enjoys exploring nature.

The couple met at a production of “A Midsummer Night’s Dream,” which was performed by a traveling cast of the Globe in Emmanuel College Gardens in Cambridge, England.

As with many others, Janowitz has had family members who are living with cancer, including both of his parents. His mother has had cancer for more than a decade and struggles with loss of appetite and weight. He has met many patients and their relatives over the years who struggle with these phenomena, which is part of the motivation for his dedication to this work.

Most cancer patients, Janowitz said, are “remarkable individuals. They adjust the way that they interact with the world and themselves when they get life changing diagnoses.” Patients have a “very reflected and engaged attitude” with the disease, which makes looking after them “incredibly rewarding.”

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From left: Carl Safina, Larry Swanson and Malcolm Bowman. Swanson who died Oct. 17, was renowned not only for his work at SBU, but also his kindly demeanor. Photo from Stony Brook University

By Daniel Dunaief

Larry Swanson has led research teams over far-flung water bodies, worked for the National Oceanic and Atmospheric Administration as a commissioned officer for 27 years and has been a fixture at Stony Brook University for over three decades. 

A former dean at the School of Marine and Atmospheric Sciences at SBU and current professor, Swanson, who is a member of New York’s Ocean Acidification Task force, was recently interviewed by Times Beacon Record News Media about his life in science.

TBR: How has science changed over the years?

Swanson: Some of the most significant things are the electronic tools that we have today. If you go back to when I was starting, if you wanted a water sample, and to collect temperature at five miles deep in the ocean, it was a very, very long tedious process. 

When you got that water sample on deck, if you wanted to simply measure salinity, you had to do a chemical titration. If you were doing that over five miles deep, below the first 1,000 meters, you might take a sample every half a mile or something like that. You couldn’t take a lot of samples. 

Now, you lower an instrument and you get a continuous trace of temperature, salinity, dissolved oxygen and other parameters, every few tenths of a meter. We are sort of overwhelmed with data now.

TBR: That must change the way people conduct experiments.

Swanson: When I first started, every data point you collected was extremely valuable and if you lost it, you really lost a lot of time, a lot of energy. It was something you could never recover. With modern instrumentation, you can do so much more and do much of it remotely; you don’t have to go to sea for seven or nine months to do that.

TBR: What are some of the biggest discoveries in your field?

Swanson: This is not necessarily things I have done. The theory of plate tectonics was established. We drilled through the crust of the earth to the mantle and we have discovered hydrothermal vents. We’ve got enough data now that we’re collecting through satellites, direct measurement in oceans in more detail, that we can really talk about changes in the global environment, whether it’s temperature increase, carbon dioxide increase and so forth. 

Those are all things that have taken place over my lifetime in oceanography. We can see what we’re doing to ourselves much more clearly today because of new technology.

TBR: What is one of the great debates in science today?

Swanson: I think trying to understand the impacts of climate change is at the forefront for everyone that’s dealing with ocean and atmospheric sciences. We don’t know all the answers and we haven’t convinced everyone it’s an issue. 

Whether or not it’s driven by people, that [debate] will continue for years to come. We’re going to bear some of the consequences of climate change before we’ve adequately convinced people that we’ve got to change our lifestyle.

TBR: What about local challenges?

Swanson: The notion of ocean acidification and how rapidly it’s changing is a local challenge. What will the consequences of it be if we don’t try to ameliorate it and what do we need to do in order to make it less of a problem? How are we going to build resiliency and reverse it?

TBR: Is there a scientific message you wish people knew?

Swanson: Scientists in general do not communicate well with the public and part of the problem is because we speak in jargon. We don’t talk to [the public] in proper ways that meet their level of understanding or knowledge. We’ve done that poorly. 

For another thing, scientists can be faulted with regard to developing policy. The scientists’ work is never done. If you go to Congress and they ask, “What are we going to do to fix the problem?,” scientists will say, “Give me more money for research and I’ll get back to you.” 

So, there’s a disconnect in terms of time frames over which we operate. [Members of Congress] operate 2 to 4 years out, while scientists operate sometimes over lifetimes. We haven’t been able to bridge that gap.

TBR: Is that improving at all?

Swanson: One of the great things that Stony Brook now has is the Alan Alda Center for Communicating Science, which is helping all the scientists here that are willing to participate in trying to do a better job of communicating. It’s making a difference and having an impact that is meaningful. It’s always good to try to put your science in the most simplistic terms possible, even if it’s a drawing or cartoon that’s helpful.

TBR: What are your future goals?

Swanson: I am hopeful  the new task force can come up with a meaningful ocean acidification action plan. I’m very pleased to be part of that group.

TBR: If you were to start your oceanography career today, what would you do differently?

Swanson: If I were to start over, I would get a master’s degree in oceanography, not a doctorate, and then I would try to get an environmental law degree. The reason I would probably do that is that I think environmental law is the best way to make an immediate impact on society. I firmly believe that one should not be an environmental lawyer until one is a fairly good scientist.

TBR: How many more years before you retire?

Swanson: I’d say a maximum of three and a minimum of one. I’m often asked, “Why are you still working?” First of all, I enjoy it and I think one of the exciting things about being an oceanographer is that there’s never been a dull day. 

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Hyunsik Kim and Erin Kang. Photo from Matthew Lerner’s lab

By Daniel Dunaief

This is the second half of a two-part series on autism research conducted by Hyunsik Kim and Erin Kang.

 Last week we focused on the work of Stony Brook University graduate student Hyunsik Kim, who used three criteria to diagnose autism. This week we will feature the work of another SBU graduate student in the Department of Psychology, Erin Kang, who specifically explored the types and severity of communication difficulties autistic children have. 

Words and the way people use them can offer clues about autism. Looking closely at pronoun reversals, speech delays, perseveration and 10 other characteristics, Kang determined that the number of features was a “powerful predictor of an autism spectrum disorder diagnosis.” 

In a paper published online in the Journal of Clinical Child & Adolescent Psychology, Kang grouped children from 6 to 18 years old into different subgroups based on their communication patterns and used a statistical method that allows the data to “speak for itself,” in terms of finding groups based on the patterns of how the communication difficulties are associated and to classify them.

According to Kang, heterogeneity is an important feature of autism spectrum disorder. “There has been a greater effort into understanding whether subgroups exist in ASD populations,” she explained in an email. By examining the atypical communication characteristics, she found four subgroups. These groups differed from each other, not only with autism, but on multiple measures, including the occurrence of anxiety or depression and with intellectual disabilities.

The communication difficulties occur at different rates within the autism children throughout Long Island that Kang studied.

Kang said her work has been “building on the previous literature,” although many of the previous studies focused on characterizing autism for children who were younger than 6.

“There are few studies on specific symptoms (e.g., stereotyped speech) across the body of literature,” she explained, adding that she’s passionate about exploring the trajectory of development over time with or without intervention. 

She and her co-authors, Ken Gadow and Matthew Lerner, who are also at Stony Brook University, are working on a follow-up paper that attempts to explore how changes in the pattern of communication challenges examined in the paper relate to other clinical aspects and outcomes.

Kang believes her results have clinical implications that will help in understanding autism. Atypical communication features are a good predictor of diagnostic status. “This can provide an advantage in assessing social communication profiles in autism,” she said. “It’s hopefully valuable in a low-resource setting.”

Parents might be asked 13 questions on a checklist, which could serve as an initial screening for more comprehensive autism evaluations, rather than a multiple checklist that could take a while for parents to complete. The different categories had specific features that distinguished them. 

“There’s been quite a bit of work in the speech and language field,” said Lerner, an associate professor of psychology, psychiatry and pediatrics in the Department of Psychology at Stony Brook University and Kang’s mentor. “This approach allowed us to ask about some of the specific types of language differences we often see.”

Lerner said what Kang found is that specific characteristics do tend to cluster together in “interesting and unique ways that can tell us more about the communicative phenotype of autism.”

One of the groups, which she called “little professors,” had speech patterns with considerable perseveration. In perseveration, a person repeats a word or phrase, even when a question or stimulus that might elicit that phrase no longer continues. As an example, Dustin Hoffman in the movie “Rain Man” frequently repeated the number of minutes until Judge Wapner was on TV.

“These kids would benefit more from a group-based social skills intervention that specifically integrated interacting with peers,” Kang said. People in this group had the highest percentage of wanting a friend, but difficulty with relating to peers.

“They will benefit especially from interventions that help them build skills in interacting with peers,” she explained.

She also suggested that the best way to make a reliable diagnosis is to collect as much information as possible, which could include observations and electrophysiological data.

Kang acknowledged that some of the responses from the parents or teachers of people with autism contain bias. “There can be a lot of potential especially in terms of these subjective measures,” she said.

Indeed, through Lerner’s lab, Kang has been trying to include more uses of neurological measures and other methodology that is less subject to biases.

“Hopefully, by looking at these more objective measures, we can help integrate information from these different levels,” she said.

A resident of East Northport, Kang lives with her husband, musician Sungwon Kim, who works as a freelancer on Broadway musicals. The couple, who have a young son, met in Boston when she was working at Boston Children’s Hospital and he was a student at Berklee College of Music. 

Kang’s first experience with autism was in high school, when she acted as a mentor to a second grader. When she entered college at the University of California at Berkeley, she studied molecular and cellular biology and psychology.

Lerner said that Kang is a “truly remarkable young scholar” and is “among the best I’ve seen at her stage to be able to look at her clinical experiences, which drive the questions that strike at the core of how we understand and treat autism.”

Lerner appreciates how she is driven to understand autism from neurons in the brain all the way up to the classification and treatment.

“She is somebody who is completely undaunted by taking on new questions or methodologies because she has an idea of what they’re going to mean,” Lerner said. “She has worked with [autistic children] and has tried to understand where they are coming from.”

Kang questions assumptions about what autism is, while also exploring its development.

“She is able to see and discover clinical strengths that manifest in the kinds of questions she asks,” explained Lerner. “She is a part of the next generation of where my field is going, and I hope we can catch up to her.”

Kang appreciates the work-life balance she has struck on Long Island, where she feels like the pace of life is “quiet and calm during the week,” while it’s close enough to New York City to enjoy the cultural opportunities.

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From left, Hyunsik Kim, Associate Professor Matthew Lerner and Erin Kang. Photo from Lerner’s lab

By Daniel Dunaief

This is part one of a two-part series on autism research conducted by Hyunsik Kim and Erin Kang.

If someone in a family behaves in ways that are difficult to understand, the family might look for a support group of people with similar characteristics, visit a doctor or seek to document and understand patterns.

Finding a doctor who has seen these types of behaviors, speech patterns or actions before could provide comfort, as the physician may either engage in a course of treatment or provide context and understanding for the current behaviors. The doctor may also offer advice about any likely changes in behaviors in the near or distant future.

For researchers, understanding a range of symptoms, some of which might be below the threshold to meet a specific diagnosis, can lead to a more specific awareness of a condition, which could help guide patients toward an effective treatment.

Hyunsik Kim and Erin Kang, graduate students in the Department of Psychology at Stony Brook University, recently published papers examining autism, hoping to get a more specific understanding of subtle differences and symptoms.

Kim was looking for a better way to conceptualize autism. He used advanced statistical methods to compare three theoretical perspectives to find the one that best characterized the symptoms.

“According to my study, autism is not an all-or-nothing phenomenon, but is dimensional [and is] comprised of three related spectra of behaviors,” he explained. 

Researchers can characterize everyone’s autism symptoms through a combination of levels in each domain.

Each of these three areas can range from very mild to severe.         As an analogy, Kim suggested considering the quality of being introverted. A person can be mildly, moderately or highly introverted, which offers a continuum for the dimension of introversion.

In a dimensional approach that involves exploring these three different categories, researchers can get a better understanding of the symptom profiles.

“For decades, people thought of autism as purely categorical,” said Matthew Lerner, an associate professor of psychology, psychiatry and pediatrics in the Department of Psychology at Stony Brook University. “You either have it or you don’t. In fact, autism was thought of as the easiest diagnosis to make.”

Kim, however, has “a goal of answering the fundamental question: what are we talking about when we’re talking about autism?” Lerner said. “Slowly, autism has morphed from the most categorical to the most dimensional. Literally, people talk about the spectrum when they talk about autism.”

With a dimensional approach based on levels of the three major domains for diagnosing autism, Kim suggested that researchers and doctors could better understand people who fall just below the current diagnosis for autism.

“It’s especially important to identify individuals who show a borderline range of symptoms, who barely fail to meet the diagnostic criteria of a given disorder, and provide them with appropriate treatments,” Kim explained.

Ideally, he hopes a dimensional approach incorporates the severity of symptoms into the current diagnostic system to promote better treatment procedures and outcomes.

Kim recognized that he could have just as easily created a dimensional approach that incorporates a greater number of criteria. His statistical analysis, however, revealed that the three dimensions provide the parsimonious explanation about autism symptoms.

Kim analyzed data from a parent questionnaire. He recognized that self-reporting by parents may underestimate or overestimate the severity of symptoms. He believed the over and under estimate of symptoms likely “evened out.”

Lerner suggests this multidimensional approach has numerous implications. For starters, it can help capture more of the types of symptoms in a diagnosis. It can also highlight the specific area of autism a clinician might want to target.

“We should be focusing on the factors that are most relevant for the individual and which are getting in their way,” Lerner said.

Treating autism broadly, instead of focusing on specific symptoms, may be “misguided,” Lerner added. A more specific characterization of autism could also help advance the field of neurogenetic research. “With more contemporary genetic analysis, we can use findings like this as a road map for what those genetic differences mean,” he said.

For his next step, Kim hopes to expand this work to observational data, adding that to the existing pool of information from parental questionnaires.

“People go on a home visit and take video of autistic kids interacting with others,” Kim said. “We can have some people code their behavior.”

More broadly, Kim would like to answer fundamental questions about the classification and conceptualization of mental disorders by using advanced quantitative modeling and other data-driven approaches. He believes a factor may represent a person’s vulnerability to developing a specific mental disorder.

A high level of this factor, combined with life stressors or adversity, would make it more likely that a person develops a disorder. As someone who studies psychology, Kim said he is well aware of his own emotional patterns and he tries to use his training to help himself cope.

He is not particularly comfortable doing public speaking, but he tells himself that whatever anxiety he feels is normal and that his practice, knowledge and expertise should allow him to succeed.

A resident of Middle Island, Kim lives with his wife Jennifer. The couple has two young children. Kim describes his wife as a “really good” amateur baker, who bakes cakes, muffins, cookies, macaroons, chiffon cakes and more. He has encouraged her to start her own YouTube channel and one day they hope to open a bakery that is online and offline.

As for his autism work, he hopes the dimensional approach is “incorporated into the assessment stage so that individuals do not merely receive a diagnosis, but are informed of their unique symptom profiles, so that clinicians can take them into consideration.” 

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Markus Seeliger with a model of a protein kinase. Photo from SBU

By Daniel Dunaief

They are like couples looking for each other on a dating website. Each side could theoretically find a range of connections. The focus in this dating game, however, has heavily favored understanding the preferences of one side. 

Markus Seeliger, an associate professor in the Department of Pharmacological Sciences at the Stony Brook University Renaissance School of Medicine, has taken important steps to change that, albeit in a completely different area. Instead of working with two people who are searching for a date, Seeliger studies the interactions among protein kinases, which are like switches that turn on or off cellular signals, and inhibitors, which researchers and drug companies are creating to slow down or stop the progression of diseases.

Markus Seliger

Most scientists have looked at the pairing of these molecules and protein kinases from the perspective of the inhibitor, trying to figure out if it would bind to one of the 500 protein kinases in the human body.

Seeliger, however, is exploring the coupling from the other side, looking at the selectivity of the kinases. He published recent research in the journal Cell Chemical Biology.

“People have only ever looked at the specificity from the point of view of an inhibitor,” Seeliger said. “We’ve turned it around. We’re looking at it from the perspective of kinases,” adding that kinases have been important drug targets for decades.

In an email, Michael Frohman, a SUNY distinguished professor and the chair of the Department of Pharmacological Sciences, applauded Seeliger’s efforts and said his research “is representative of the innovative work going on in many of the labs here.” 

On a first level, Seeliger discovered eight kinases that bind to a range of potential inhibitors, while the others are more selective.

Within the smaller group that binds a range of inhibitors, there was no sequence relationship between the base pairs that formed the kinases. The kinases are also not closely related in the cellular functions they regulate. They all trigger similar signaling cascades. 

Seeliger wanted to know why these eight kinases were four to five times more likely to couple with an introduced inhibitor than their more selective kinase counterparts. The Stony Brook scientist performed a three-dimensional analysis of the structure of one of these kinases at Brookhaven National Laboratory.

“They have a very large binding pocket that can accommodate many different inhibitors,” Seeliger said. Indeed, he discovered this higher level of receptivity by separating out this group of eight, which also had more flexible binding sites. If the match between the configuration of the inhibitor and the kinase isn’t perfect, the kinase can still find a way to allow the molecule to connect.

For any potential inhibitor introduced into the human body, this more flexible and accommodating group of kinases could cause unintended side effects regardless of the level of specificity between the inhibitor or drug and other targets. This could have health implications down the road, as other researchers may use the properties of these kinases to switch off programs cancer or other diseases use to continue on their destructive paths.

“Studies point to the roles of protein kinases as driving (to at least allowing and permitting) cancer growth and development,” Yusuf Hannun, the director of the Stony Brook University Cancer Center, explained in an email. “Therefore, one needs to inhibit them.”

Hannun described Seeliger as “very rigorous” and suggested he was an “up and coming scientist” whose “novel approach” shed significant new light on protein kinases.

In his research, Seeliger’s next step is to look at the existing database to see what other groups of kinases he finds and then determine why or how these switches have similarities to others in other systems or regions of the body.

Seeliger likened kinases to a control panel on a space shuttle. “Nothing about the sequence tells you about the role of the switches,” which would make it difficult for astronauts to know which switch to turn and in what order to bring the shuttle home.

Another question he’d like to address involves a greater understanding of the complexity of a living system. So far, he’s looked at properties of these kinases under controlled conditions. When he moves into a more complex environment, the inhibitors will likely interact and yield unexpected binding or connections.

Frohman appreciated Seeliger’s overall approach to his work and his contribution to the field. He cited the popularity of a review article Seeliger wrote that documents how drug molecules find their target binding site. Frohman said this work, which was published in the Journal of the American Chemical Society, was cited over 400 times in other articles.

Seeliger has been “very dedicated to moving this field forward. We were very excited about the topic and have been very pleased with the work he’s done on it since arriving at SBU,” Frohman said.

A resident of Stony Brook, Seeliger lives with his wife Jessica Seeliger, an assistant professor in the Department of Pharmacological Sciences who works on developing drugs for tuberculosis. The couple has two young children.

“We are all very happy they are both here as independent scientists,” Frohman added.

Indeed, Hannun called Jessica Seeliger an “outstanding and highly talented scientist,” as well.

Seeliger grew up in Hanover, Germany. He became interested in science in high school when he watched “The Double Helix,” which showed the development of the structural model of DNA.

His lab currently has two postdoctoral researchers and two doctoral candidates. Ultimately, Seeliger hopes his research helps establish an understanding of the way various kinases are functionally similar in how they interact with drugs.

“We wish we would be able to design more specific inhibitors without having to test dozens and dozens of compounds by trial and error,” he explained. He hopes to continue to build on his work with kinases, including exploring what happens when mutations in these switches cause disease.

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Malagasy women break up granite stones to be used as gravel in the construction of the IUCN research center. Photo from Ali Yapicioglu

By Daniel Dunaief

After considerable planning, fundraising and coordinating, Patricia Wright welcomed a star-studded group of scientists, government officials and conservationists recently for the roof raising of the new IUCN Saving Our Species Biodiversity Research Center in Madagascar.

The building, which cost about $1 million, is a part of Centre ValBio, which is a conservation and research center Wright, a Distinguished Service Professor and award-winning researcher  at Stony Brook University, founded in 2003. CVB is near Ranomafana National Park in the southeastern part of the African island nation.

Above, a sketch of the IUCN Saving Our Species Biodiversity Research Center/Image courtesy of InSite Architecture

When it is completed this summer, the new building, which includes a green roof balcony and a central staircase and breezeway, is expected to provide research facilities for about ten scientists. They will study insects and plants, frogs and lemurs, the primates Wright has observed, researched, and shared with the public for over 30 years. Visiting scientists can apply to work at the center starting in September.

Russell Mittermeier, the Chief Conservation Officer at Global Wildlife Conservation and a research professor in the Department of Anatomical Sciences at Stony Brook, suggested that these types of efforts pay dividends.

It’s “hard to predict what will be found but history has shown us that there are endless benefits to conserving biodiversity and maintaining healthy ecosystems,” Mittermeier, the Chair of the IUCN/ SSC Primate Specialist Group, explained in an email from Madagascar.

Conservationists credit Wright with adding the new Biodiversity Centre to the larger research and conservation presence in Madagascar.“Wright was instrumental” in developing the facility, said Christoph Schwitzer, the Director of Conservation at Bristol Zoological Society and the Deputy Chair and Red List Authority Coordinator of the IUCN SSC Primate Specialist Group. “Without her, it wouldn’t be there. She started this whole project.”

The IUCN expressed its appreciation for the work Wright put in to continue to build on her track record of conservation.

At IUCN, “we highly value our collaboration with [Wright] and we understand she has established a good relationship with the Park Manager of Ranomafana National Park,” Remco Van Merm, the Coordinator of IUCN’s Saving Our Species initiative, explained in an email.

Save Our Species funds projects that “enhance the conservation of threatened species,” Van Merm added. “In the case of the new SOS Biodiversity Research Centre at Centre ValBio in Madagascar, the research that will be carried out will contribute greatly to the conservation of lemurs and other threatened biodiversity” in the national park.

Wright insisted that the new biodiversity center use local materials and workers, as she did with the construction of Namanabe Hall, its much larger sister building on the CVB campus.

Wright “wants to have the local villagers be involved in the process,” said Ali Yapicioglu, a partner at InSite, an architectural firm in Perry, New York who worked on both buildings. The sand is from the river, while the gravel comes from granite pieces that local women break down into smaller pieces.

In addition to local labor and materials, Wright ensured that InSite provided education to Malagasy residents, which included classes at the construction site. Through the building process, InSite also trained electricians.

While CVB, which is the largest biodiversity research center in the country, is well-established, it took considerable work on the Stony Brook scientist’s part to create it.

Schwitzer said Wright “fought against various forces trying to set this center up and she succeeded. She’s an excellent fundraiser.”

Madagascar has presented numerous challenges for conservation, in large part because of the changes in governments.Mittermeier recently had a “good discussion” with Andry Rajoelina about biodiversity just before Rajoelina was inaugurated as president of Madagascar last week. “Let’s see what he does” on biodiversity, Mittermeier explained. The Stony Brook professor plans to recommend that Rajoelina visit Ranomafana. 

For visitors, the CVB site offers ecotourists a firsthand opportunity to observe the charismatic lemur species, which are a part of the “Madagascar” animated films and were also the subject of an Imax movie about Wright’s work called “Island of Lemurs: Madagascar.”

“People who go there can see quite a few interesting lemur species in the wild,” Schwitzer said, adding that the station also gives Schwitzer “hope for lemur conservation,” he said.

The SOS lemur program originated with a 2013 published report, which included permanently managed field stations as a critical element. Research and field stations deter logging and lemur hunting, while also contributing scientific information that the government can use to set policies and make informed decisions, he added.

The lemur action plan includes the construction of this building. Schwitzer indicated that these types of initiatives, spread throughout the country, are critical to protecting species under various pressures, including habitat destruction.

“If we don’t keep up the effort, we could very well lose one,” Schwitzer said. He hastened to add that no lemurs have gone extinct in modern times, but “we can’t become complacent.” Indeed, the rarest of lemurs, the Northern Sportive Lemur, is down to 60 individuals in the world.

In the future, Schwtizer hopes Malagasy leaders and institutions will apply for international funding for themselves, as they drive the conservation goal forward.

This September, Wright will also finish an Education Center on the lower campus. On the upper campus, which is just across the road, she is building a wildlife center that will include a vet clinic, a frog breeding center, a mouse lemur facility, and a climate and drone center. The facility will also include bungalows for long-term researchers.

In addition to providing a field station for researchers, the site will also provide information accessible to the public.

“We are producing online identification systems like iNaturalist and also putting vocalizations and videos of the wildlife online,” Wright explained in an email.

Schwitzer said he has attended meetings where Wright has shared her vision for CVB with scientists and conservationists.

“Everybody looks at this and says, ‘This is cool. I want to do something like that,’” Schwitzer said.

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From left, graduate students Prakhar Avasthi, Alisa Yurovsky, Charuta Pethe and Haochen Chen with director Steven Skiena, center. Photo by Gary Ghayrat/Stony Brook University

By Daniel Dunaief

Steven Skiena practices what he teaches. Named the director of the Institute for AI-Driven Discovery and Innovation in the College of Engineering and Applied Sciences at Stony Brook University, Skiena is using artificial intelligence to search for three staff members he hopes to hire in this new initiative.

He is looking for two tenured professors who will work in the Department of Computer Science and one who will be a part of the Department of Biomedical Informatics.

“We hope to use an artificial intelligence screen,” which Skiena calls a Poach-o-matic to “identify candidates we might not have thought of before. Ideally, the program will kick up a name and afterward, we’d bump our hand on our head and say, ‘Of course, this person might be great.’”

Steven Skiena. Photo from SBU

Artificial intelligence and machine learning have become popular areas in research institutions like Stony Brook, as well as in corporations with a wide range of potential applications, including in search engine companies like Google.

Skiena, who is a distinguished teaching professor, said he has “several candidates and we’re now actively interviewing,” adding that many departments on campus have faculty who are interested in applying machine learning in their work.

“There’s been an explosion of people from all disciplines who are interested in this,” Skiena said. He recently met with a materials scientist who uses machine learning techniques to improve experimental data. He’s also talked with people from the business school and from neuroscience.

SBU students have also shown considerable interest in these areas. Last semester, Skiena taught 250 graduate students in his introduction to data science class.

“This is a staggering demand from students that are very excited about this,” he said. Machine learning has become a “part of the standard tool kit for doing mathematical modeling and forecasting in many disciplines and that’s only going to increase.”

In an recent email, Andrew Schwartz, a core faculty at the institute and an assistant professor in the Department of Computer Science at Stony Brook, said he believes bringing in new faculty “should attract additional graduate students that may become future leaders in the field.”

Increasing coverage of AI beyond the current expertise in vision, visualization, natural language processing and biomedical engineering can “go a long way. There are a large amount of breakthroughs in AI that seemingly come from taking an idea from one subfield and applying it to another.” Schwartz appreciates the impact Skiena, who is his faculty mentor, has had on the field.

Skiena has “managed to contribute to a wide range of topics,” Schwartz explained. His book, “The Algorithm Design Manual,” is used by people worldwide preparing for technical interviews. Knowing this book thoroughly is often a “suggested step” for people preparing to interview at Google or other tech companies, Schwartz added.

The students in Schwartz and Skiena’s labs share space and have regular weekly coffee hours. Schwartz appreciates how Skiena often “presents a puzzling question or an out-of-the-box take on a question.”

The core technical expertise at the institute is in machine learning, data science, computer vision and natural language processing.

The creation of the institute shows that Stony Brook is “serious about being one of the top universities and research centers for expertise in AI,” explained Schwartz.

A few years ago, researchers realized that the artificial intelligence models developed biases based on the kind of training data used to create them. “If you’re trying to build a system to judge resumes to decide who will be a good person to hire for a certain type of job” the system has a danger of searching for male candidates if most or all of the people hired had been male in the past, Skiena explained.

Unintentional biases can creep in if the data sets are skewed toward one group, even if the programmer who created the artificial intelligence system was using available information and patterns.

In his own research, Skiena, who has been at Stony Brook since 1988, works on natural language processing. Specifically, he has explored the meaning of words and what a text is trying to communicate.

He has worked on sentiment analysis, trying to understand questions such as whether a particular political figure who receives considerable media coverage is having a good or bad week.

Another project explores the quality of news sources. “Can you algorithmically analyze large corpuses of news articles and determine which are reliable and which are less so?” he asked. 

One measure of the reliability of a news source is to determine how much other articles cite from it. “It is important to teach skepticism of a source” of news or of data, Skiena said. 

“When I teach data science, a lot of what I teach includes questions of why you believe a model will do a good thing and why is a data source relevant,” he added.

A resident of Setauket, Skiena lives with his wife Renee. Their daughter Bonnie is a first-year student at the University of Delaware, where she is studying computer science. Their tenth-grade daughter Abby attends Ward Melville High School and joins her father for bike rides on Long Island.

Skiena, who grew up in East Brunswick, New Jersey, said he appreciates the university community. By working in the AI field, Skiena, who has seven doctoral students in his lab, said he often observes glitches in online models like article classification on Google News or advertisements selected for him on a website to try to figure out why the model erred. He has also developed a sense of how probability and random events work, which he said helps him not overinterpret unusual events in day-to-day life.

As for his work at the institute, Skiena hopes Stony Brook will be recognized as a major player in the field of machine learning and areas of artificial intelligence. “We have good faculty in this area already and we’re hiring more. The hope is that you reach critical mass.”

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Jason Sheltzer. Photo by ©Gina Motisi, 2018/CSHL

By Daniel Dunaief

A diagnosis of cancer brings uncertainty and anxiety, as a patient and his or her family confront a new reality. But not all cancers are the same and not all patients are the same, making it difficult to know the severity of the disease.

As doctors increasingly focus on individual patient care, researchers are looking to use a wealth of information available through new technology to assist with everything from determining cancer risks, to making early diagnoses, to providing treatment and aftercare.

Jason Sheltzer, a fellow at Cold Spring Harbor Laboratory, and his partner Joan Smith, a senior software engineer at Google, have sought to use the genetic fingerprints of cancer to determine the likely course of the disease.

By looking at genes from 20,000 cancer patients, Sheltzer and Smith found that a phenomenon called copy number variation, in which genes add copies of specific long or short sequences, is often a good indicator of the aggressiveness of the cancer. Those cancers that have higher copy number variation are also likely to be the most aggressive. They recently published their research in the journal eLife.

While the investigation, which involved work over the course of four years, is in a preliminary stage, this kind of prognostic biomarker could offer doctors and patients more information from which to make decisions about treatment. It could also provide a better understanding of the course of a disease, as copy number variation changes as cancer progresses.

“The main finding is simply that copy number variation is a much more potent prognostic biomarker than people had realized,” Sheltzer said. “It appears to be more informative than mutations in most single genes.”

Additionally, despite having data from those thousands of patients, Sheltzer and Smith don’t yet know if there’s a tipping point, beyond which a cancer reaches a critical threshold.

Some copy number changes also were more problematic than others. “Our analysis suggested that copy number alterations affecting a few key oncogenes and tumor suppressors seemed to be particularly bad news for patient prognosis,” Sheltzer said, adding that they weren’t able to do a clinical follow-up to determine how genes changed as the cancer progressed. 

“Hopefully, we can follow up this study, where we can do a longitudinal analysis,” he said.

Joan Smith. Photo by Seo-young Silvia Kim

Smith, who has written computer code for Twitter, Oracle and now Google, wrote code that’s specific to this project. “The analysis we’ve done here is new and is on a much more significant scale than the analysis we did in the past,” she said.

Within the paper, Smith was able to reuse parts of code that were necessary for different related experiments. Some of the reusable code cleaned up the data and provided a useful format, while some of the code searched for genetic patterns.

“There is considerable refinement that went into writing this code, and into writing code in general,” she explained in an email.

Smith has a full-time job at Google, where she has to clear any work she does with Sheltzer with the search engine. Before publication, she sent the paper to Google for approval. She works with Sheltzer “on her personal time,” and her efforts have “nothing to do with Google or Google Tools.”

The search engine company “tends to be supportive of employees doing interesting and valuable external work, as long as it doesn’t make use of any Google confidential information or Google owned resources,” including equipment supplies or facilities, she explained in an email.

The phenomenon of copy number variation occurs frequently in people in somatic cells, including those who aren’t battling a deadly disease Sheltzer said. “People in general harbor a lot of normal copy number variation,” he added.

Indeed, other types of repetitive changes in the genome have played a role in various conditions.

Some copy number variations, coupled with deletions, can be especially problematic. A tumor suppressor gene called P53, which is widely studied in research labs around the world, can accumulate copy number variations.

“Patients who have deletions in P53 tend to accumulate more copy number alterations than patients who don’t,” Sheltzer said. “A surprising result from our paper is that copy number variation goes above and beyond P53 mutations. You can control for P53 status and still find copy number variations that act as significant prognostic biomarkers.”

The copy number variations Sheltzer and Smith were examining were affecting whole genes, of about 10,000 bases or longer.

“We think that is because cancers are Darwinian,” explained Sheltzer. “The cells are competing against one another to grow the fastest and be the most aggressive. If a cancer amplifies one potent oncogene, it’s good for the cancer. If the cancer amplifies 200 others, it conveys a fitness penalty in the context of cancer.”

Smith is incredibly pleased to have the opportunity to contribute her informatics expertise to Sheltzer’s research, bringing together skill sets that are becoming increasingly important to link as technology makes it possible to accumulate a wealth of data in a much shorter term and at considerably lower expense.

Smith has a physics degree from MIT and has been in the technology world ever since.

“It’s been super wonderful and inspiring to get to do both” technology work and cancer research, she said.

The dynamic scientific duo live in Mineola. They chose the location because it’s equidistant between their two commutes, which are about 35 minutes. When they are not working, the couple, who have been together for eight years and have been collaborating in their research for almost all of them, enjoy biking, usually between 30 to 60 miles at a time.

Sheltzer greatly appreciates Smith’s expertise in using computer programs to mine through enormous amounts of data.

They are working on the next steps in exploring patient data.

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Left, Lauren Hale; above, teenagers need 8 to 10 hours of sleep every night.

By Daniel Dunaief

Around this time of year, people shop for gifts for others, decorate for the holidays, and generally raise their stress level as they search for the perfect holiday plan. Somewhere in between the to-do lists and the to-buy lists, some ambitious holiday revelers also consider making a for-me list, or the equivalent of a collection of pre-New Year’s resolutions.

Often appearing in that collection is a desire to live better, to stick to a diet, to embark on a healthy lifestyle and to enjoy the moments, big and small, on the horizon in 2019.

Often overlooked in the end-of-the-year cycle is if people hope for the chance to get more sleep. That, however, may make many of those other goals — weight loss, better work performance or a calm reaction to events — more manageable.

Times Beacon Record News Media recently spoke with Stony Brook University sleep expert Lauren Hale, who is a professor of family, population and preventive medicine and teaches in the Program in Public Health at Stony Brook. Hale is also the editor-in-chief of Sleep Health.

TBR: You recently published a journal article in Sleep Health in which you linked late night social media use by National Basketball Association players with their performance. Can you talk about that?

LH: This is a coarse estimate at showing that being up late is associated with worse outcomes. It’s not necessarily saying it’s only because they’re staying up late.

TBR: How much data did you examine?

LH: We looked at seven seasons of data. We were interested in how players did on games following late night tweets compared to games following no tweeting activity. … If your shooting percentage drops by 1.7 percentage points, that could be the difference between a win and a loss.

TBR: Have you extended this work to any teams?

LH: I’m talking with the Stony Brook Athletics Department to incorporate sleep hygiene into the players’ routines. We’re hoping to start with men’s basketball in the spring of 2019.

TBR: What are some sleep strategies?

LH: There is a list of sleep hygiene strategies. Many will seem like common sense. They include having a regular bedtime, which you calculate based on when you need to wake up and how many hours of sleep you need to get, limiting caffeine, tobacco and alcohol… [They also include] not eating too many heavy foods right before bed, exercising, preferably earlier in the day and reducing screen time at night.

TBR: Does the optimum number of hours of sleep change with age?

LH: Yes. Little kids sleep a lot and need a nap. As they get older, they lose the nap, but still need to sleep 9 to 11 hours. Teenagers need 8 to 10. Adults typically need 7 to 9 hours.

TBR: How do you manage sleep in your house?

LH: We have young children, so we know how challenging it can be. The younger one goes to day care and naps two hours. It’s hard to get him to go to sleep. I’m not good about putting my phone down in the hour before bed. We do have a charging location downstairs in our house, so the devices are limited in the bedroom. The children don’t watch screens in the half hour or hour before bed.

TBR: What’s the link between sleep and weight loss?

LH: Sleep duration is inversely associated with weight gain. Individuals not getting enough sleep are more likely to gain weight. The choices of food you make when you’re sleep deprived are worse. Your hormones make you hungrier and less full. The choices you make also show less self-discipline. When you’re sleep deprived, you’re unlikely to make yourself a salad.

TBR: Did you see the recent study that links sleep and anger?

LH: It is consistent with some work I’m doing on teenagers. We know sleep is important for emotional regulation. I’m not surprised that it’s linked.

TBR: Should people who want to lose weight focus on sleep?

LH: There are obesity experts who have taken on sleep as one of the three pillars of optimal health: sleep, exercise and diet. Among those three, sleep is usually the one that’s the most overlooked.

TBR: How else does sleeping affect weight?

LH: If you want to stick to your diet, stay on a regular sleep schedule that’s going to give you the sleep you need. Eating during normal activity phases — daytime for humans — prevents obesity. 

TBR: Is there evidence that too much sleep can be bad for health as well?

LH: There’s not good evidence of a casual link between long sleep and poor health. There is strong evidence that there’s an association, due to reverse causality, that shows that sicker people need more sleep. If you’re sleeping more than 11 hours, that might be a sign that you have an underlying condition that is contributing to you needing 11 hours.

TBR: What is your next sleep-related study?

LH: My primary current research is about studying teenagers and the causes and consequences of their insufficient sleep. Some of the factors that affect adolescent sleep are screen-based media use and early school start times.

TBR: Could sleep patterns be an important indicator of health?

LH: We would love to see sleep treated as a vital sign, in which every patient gets asked. It’s not asked about and it’s not, in and of itself, sufficient [for a specific diagnosis]. It’s a good marker of well-being.

TBR: Did people believe a certain amount of sleep was optimal 50 years ago and has that number risen or fallen since then?

LH: The number of recommended hours has been relatively consistent over time. There’s just more science to support the recommendations now.

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Danny Bluestein and Wei-Che Chiu, a Stony Brook biomedical engineering doctoral student, with ventricular assist devices. Photo from SBU

By Daniel Dunaief

Some day, a doctor may save your life, repairing a calcified heart valve that jeopardizes your health. But then, the doctor may owe his or her latest lifesaving procedure to the work of people like Danny Bluestein, a professor in biomedical engineering and the director of the Biofluids Laboratory at Stony Brook University, and an international team of colleagues.

The group is working on restoring blood flow from the heart to the body using approaches for patients for whom open heart surgery is not an option.

Recently, the National Institutes of Health awarded the research crew a five-year $3.8 million grant to work on a broad project to understand ways to improve transcatheter aortic valve replacements, or TAVR, while reducing or minimizing complications from the procedure.

Danny Bluestein with his wife, Rita Goldstein. Photo from D. Bluestein

The grant is “not just about developing a new device, which we’ve been developing already for several years, but it’s also developing it in such a way that it answers challenges with disease and what clinical problems current technology offers solutions for,” Bluestein said.

TAVR provides a prosthetic valve for high-risk surgery patients. Like stents, TAVR is inserted through an artery, typically near the groin, and is delivered to the heart, where it improves the efficiency of an organ compromised by calcification on a valve and on the aorta itself.

Patients who have been candidates for TAVR are usually over 70 and often struggle to walk, as their hearts are enlarged and lose flexibility.

TAVR surgeries are performed in as many as 40 percent of such operations in some parts of Europe and the United States. The numbers have been increasing in the last couple of years as the technology has improved in different iterations of TAVR.

These valves are not only helping high-risk patients, but they are also assisting moderate and lower risk candidates.

Doctors have used TAVR for off-label uses, such as for people who have congenital difficulties with their valves, and for people who have already had open heart surgeries whose replacement valves are failing and who may be at risk for a second major heart operation.

Recovery from TAVR is far easier and less complicated than it is for cardiac surgery, typically requiring fewer days in the hospital.

Indeed, numerous researchers and cardiologists anticipate that this percentage could climb in the next several years, particularly if the risks continue to decline.

The team involved in this research effort is working with a polymer, hoping to reduce complications with TAVR and develop a way to tailor the valve for specific patients.

“If you’re a polymer person like me, you know we can make this work,” said Marvin Slepian, the director of the Arizona Center for Accelerated BioMedical Innovation at the University of Arizona. Slepian is pleased to continue a long collaboration with Bluestein, whose expertise in fluids creates a “unique approach to making something happen.”

The tandem is working with Rami Haj-Ali, the Nathan Cummings Chair in Mechanics in the Faculty of Engineering at Tel-Aviv University in Ramat Aviv, Israel. “To enable this technology, we need to better understand the current” conditions, said Haj-Ali, who uses computer methods to study the calcium deposited on the valve to understand the stages of the disease.

The valve Bluestein is proposing includes “new designs, new simulations, and new materials” that can create “less reactions with patients and overcome” problems TAVR patients sometimes face, Haj-Ali explained.

One of the significant challenges with TAVR is that it typically only lasts about five to six years.

“The idea of the NIH and this project is to extend the built-in efficiency of such a procedure,” Bluestein said. “TAVR is moving very fast to extend its functionality and durability.”

When the valve is inserted into the body, it is folded to allow it to fit through the circulatory system. This folding, however, can damage the valve, making it fail faster than in the surgical procedure.

As a part of this research, Bluestein and his team will explore ways to change the geometry of the TAVR according to the needs of the patient, which will enhance its functionality for longer. Bluestein and others will test these changing shapes through models constructed on high-performance computers, which can test the effect of blood flowing through shapes with specific physical passageways.

“Eventually, the future would involve custom designed valves, which would be optimal for the specific patient and will extend the lifespan of such a device,” Bluestein said.

A current off-label use of the TAVR valve involves assisting people born with an aortic valve that has two leaflets. Most aortic valves have a third leaflet. People with bicuspid aortic valves develop symptoms similar to those with calcification.

Going forward, Bluestein and his team plan to design valves that are specific for these patients.

A small percentage of patients with TAVR also require pacemakers. The device can interact with the electrophysiology of the heart and impair its rhythm because it creates pressure on the tissue. It is likely pushing against special nodes that generate the heart rhythm.

These studies include exploring the mechanical stress threshold that requires implantation of a pacemaker. By moving the device to a slightly different location, it may not interfere with the heart rhythm.

A resident of Melville and Manhattan, Bluestein is married to Rita Goldstein, who is a professor of psychiatry and neuroscience at the Icahn School of Medicine at Mount Sinai. 

Bluestein was raised in Israel, where he did his doctoral work. He became intrigued by the study of the flow of blood around and through the heart because he was interested in blood as a living tissue.

As for the ongoing work, Haj-Ali is optimistic about the group’s prospects. The scientists that are a part of this effort “bring something to the table that, in combination, doesn’t exist” elsewhere, he said.

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