Power of 3

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Defeating a deadly enemy requires preventing that killer from traveling to key areas and wreaking irreversible damage. Stony Brook’s Jian Cao, an associate professor in the Department of Medicine, is seeking ways to prevent the enemy, in this case cancer, from making its deadly journey through the body.

Recognized for ground-breaking work he did in Japan, Cao has focused on understanding how to stop a tissue-degrading enzyme called matrix mettalloproteinases, or MMP.

“Understanding the scientific basis for metastasis has been the most challenging aspect of cancer research,” said Stanley Zucker, a professor emeritus in the Department of Medicine at Stony Brook who has collaborated with Cao for close to two decades. “No one has yet figured out a treatment that specifically interferes with the metastatic process.”

Cao, who was born in China and trained with a renowned Japanese biologist, Motoharu Seiki, explained that scientists have focused their attention on disrupting the catalytic site, the place where the MMP breaks apart cell-cell adhesion molecules.

Clinical trials of an inhibitor or blocker for that site failed because of a lack of selectivity. He now focuses on a different area, called a hemopexin domain, that is required for enhanced cell migration. He has developed inhibitors targeting different MMPs.

“We have identified the region that is required for MMP-mediated cell migration, then, we developed inhibitors to target this region,” he said. “We found or developed regions that specifically interfere” with their signaling pathway that leads to enhanced cell migration.

He uses a small protein and synthetic compounds that don’t destroy the enzyme, but rather render it ineffective in spreading cancer.

There are 25 forms of MMP. For breast cancer, for example, MMP-14 activates MMP-2, which activates MMP-9. Based on other research, all these MMP’s play an important role in breast cancer metastasis, Cao said. “We identified regions that are required for enhanced cell migration that are specific and selective for each MMP,” he said.

Cao said his work has generated attention from pharmaceutical companies that are hoping to develop treatments for metastatic forms of cancer. A company reached out to him recently because they “want to collaborate to license our inhibitors,” he said.

Cao’s scientific peers lauded his results and his approach. “Many top investigators in the field consider Dr. Cao to be the best scientist to have entered the rapidly expanding field of MMPs in the past 20 years,” said Zucker. “Dr. Cao gained worldwide recognition for his research contributions to Dr. Seiki’s laboratory in Japan.”

In addition to working with these MMP inhibitors, Cao also has a three-dimensional drug screening test. Cao looks to see whether drugs that might be approved for other uses might have anti-cancer properties. The National Institute of Health’s National Center for Advanced Translational Sciences created a program aimed at repurposing old drugs for new uses. He has seen some benefit from a psychiatric drug that can interfere with cell migration and can inhibit cancer invasion.

At the recent 2014 Gloria and Mark Snyder Symposium for Cancer Medicine, Cao presented his research on a gene he cloned, called CeMIP, that is normally expressed in the central nervous system.

After analyzing thousands of patients, he found that people who have a high level of this gene have a shorter survival period with breast cancer. Those with less of this gene survive longer.
Knocking out this gene in highly aggressive breast cancer in animal models causes cancers to become less invasive.

He is studying a promoter region of this gene that selectively hits the on switch. He hopes to develop a compound that interferes with the CeMIP protein.

A resident of South Setauket, Cao lives with his wife, Qiang Zhao, who is also a scientist working on cancer at Stony Brook, and their 16-year-old son Kevin.

His work often includes going to the lab seven days a week. Cao is “the hardest working scientist I’ve ever encountered,” said Zucker.

“His productivity is outstanding in terms of publication and new research grants.”

Cao believes he is on the right track to develop possible treatments to battle cancer as it spreads. “If you can stop the invasion,” he said, “you can prevent metastasis.”

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Bo Li looks closely at red and green colors. He is not preparing Christmas decorations, but rather is looking at the way different neurons in a region of the brain light up in response to an increase or decrease in fear.

An associate professor in the Neuroscience Department at Cold Spring Harbor Laboratory, Li is studying a small area in the mouse brain called the amygdala. His results may help guide pharmaceutical companies and other researchers as they look for ways to help people suffering with post-traumatic stress disorder.

In the central amygdala, he found two cell populations that likely play some role with fear. One of those cell populations promotes fear. He believes the other suppresses fear. Ongoing studies, he said, will provide answers about the other cells soon. Once he understands both, he will look for ways to affect their activity.

Understanding fear responses is just one of the areas where Li studies neurons in the brain. He also does research on animal models of depression and schizophrenia, hoping to find differences researchers can exploit to provide early detection, treatment and prevention.

Fritz Henn, a visiting professor at Cold Spring Harbor Laboratory who collaborated with Li when Li was a post-doctoral fellow, said he is a “rising star in neuroscience research.”

In post-traumatic stress disorder, people who witness or experience stressful and potentially life-threatening experiences develop a sustained level of fear, even after removed from stresses like the life-and-death struggles of war. This trauma can diminish the quality of life as people struggle with emotional scars that don’t seem to heal.

By looking at the neurons of mice, Li is able to use genetic technology to explore an area that contains about 10,000 neurons. He uses scientific advances that enable him to separate neurons in different categories. These different types of neurons are labeled by a marker, which glows in green, yellow or red. He can also use viruses that specifically recognize these neurons and enable him to see a higher or reduced activity level for these neurons in a fear response.

Using an optical fiber that is about 150 microns, which is about the thickness of a human hair, Li can shine a light on the amygdala to see signals that are then collected through a computer. His analysis allows him to record changes in the signals sent by these different types of cells. Henn called Li’s research “state of the art.”

By collaborating with other scientists at Cold Spring Harbor Laboratory to do gene sequencing, Li can look at what other proteins are expressed by these different cells.

“It’s just a matter of time to gather the data and come to conclusions,” he said. He believes this research will make substantial scientific progress in the next five years. The clinical applications will likely take longer, he predicted.

The amygdala is an area that scientists have known for a long time controls emotion and emotional memory. As a result, researchers on Long Island and elsewhere in the world are putting considerable energy and time into understanding the specific cellular functions in this region.

His work on schizophrenia presents other challenges because it’s difficult to mimic the kind of symptoms humans exhibit, including hallucinations and reasoning problems.
Li is looking at the genes linked to schizophrenia and finding similar genes in mice.

“Going from genes to behavior is a big gap,” he said. “We need to fill that in.” He is working on genes in his lab that he knows cause problems in some brain circuits to understand depression as well.

“We know a particular circuit in the brain [called the lateral habenula circuit] is important for reward, learning and punishment,” he said. “When this circuit is impaired, it can cause depression.”

Li lives on campus at Cold Spring Harbor with his wife, Shirley Guo, who is also a scientist and works for Kadmon, a biotechnology company in New York City that is developing medicines for a range of diseases and provides treatment of hepatitis C. The couple have an 11-year-old daughter, Serena, who is an avid tennis player.

Li called Cold Spring Harbor a “fantastic environment” and said it is “one of the best in the world for doing science.”

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Getting a wallet out of a back pocket, reaching up to put luggage in an overhead bin on an airplane, or waving across a parking lot to a friend are all motions that can become almost impossible for people who have frozen shoulder.

A painful and motion-limiting problem, frozen shoulder occurs mostly in women between the ages of 40 and 60. The problem is that the body is depositing extra collagen, a binding material, over the shoulder capsule, limiting motion around the joint. Typically, treatment includes a corticosteroid injection and considerable amounts of physical therapy, to loosen up the joint. If that doesn’t work, patients have gone through a surgical procedure that includes months of physical therapy afterwards.

Edward Wang, associate professor of orthopedics who treats numerous cases of frozen shoulder each year at Stony Brook Orthopaedic Associates, and Marie Badalemente, a professor in the Department of Orthopaedics who has worked to develop an enzyme cocktail to relieve the pain of a disfiguring hand disease, have teamed up to create an injection that targets that extra collagen.

The treatment uses injections of an enzyme called clostridial collagenase. The tandem have patented the treatment and are entering phase 2b of the Food and Drug Administration’s clinical trials, which are ongoing at 25 facilities throughout the United States and five in Australia. Stony Brook is still looking for volunteers to participate in the drug trial.

Kim Russo of Holbrook had surgery for one of her shoulders when she noticed an ad for the study. The treatment she’d already received included four months of physical therapy, surgery and then another four months of therapy.

When she received her first treatment, she noticed a change almost immediately. “I could tell after my first [shot] that there was something just a little different,” she said. After the second shot, she was doing so well that she didn’t need a third one, she said.

Badalemente helped develop the treatment, called Xiaflex, for a condition that also involves the build up of collagen in the hand. In Dupuytren’s contracture, people struggle with limited finger mobility. The enzyme breaks down the collagen, restoring function and flexibility to the fingers.

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Like a philosopher, Marshall Newton ponders the journey and the destination. Except that what he’s pondering often has to do with the movement of energy rather than the circuitous path through life.

A professor emeritus of chemistry at Brookhaven National Laboratory, Newton retired on January 1, 2009, but, by several accounts, that hasn’t slowed him down. He said retiring freed him up from the “important but time-consuming departmental and lab-wide committee meetings,” enabling him to “get back in depth to some scientific issues which I never had time to fully pursue in the past,” he explained.

Newton tries to understand how energy moves from one place — often at the start of photosynthesis — to a form of energy stored or used in another place. “What I do,” he explained, “is formulate mechanisms for a key process that typically occurs in almost all energy conversion processes.”

Theorists like Newton want to assess the possible pathways “for the efficient capture and conversion of energy.” Part of this conversion involves electronic transfer, which is usually coupled to heavy atoms that must go over a hill or energy barrier as part of the overall transfer process. That process represents something of an energy cost, the way a local diner might incur costs paying for electricity or gas.

Newton develops quantum mechanical models to analyze the efficiency of such processes. He has investigated molecular processes that may serve as components of new artificial photosynthesis schemes, either photochemical or electrochemical.

In artificial photosynthesis, researchers try to mimic the energy generated by plants from carbon dioxide, water and the sun.
Newton is “recognized worldwide for his scientific contributions combining his knowledge of electronic structure, electrochemistry and a wide range of other chemistry,” said James Muckerman, a senior chemist at BNL who has known Newton for close to half a century.

Newton, who started working at BNL in 1969, said that chemists used to be “in the dark ages” about calculating what happened on an incredibly small time scale. Theory and experiment have “bootstrapped” each other in achieving finer and finer distance and time scale, he said.

The benefit of all the theoretical work with computer simulations and models is that it can help guide future design ideas for solar cells or other energy capturing and transferring processes.

Theorists can “turn over [their results] to engineers and say, ‘This is what you should do to make optimal energy material,’” Newton offered. That, he added, is easier said than done.

When scientists try to move energy or charge, the standard problem is the dissipation or loss of that energy along the way. It’s akin to carrying a bag of groceries home from the store and bumping into walls along the way. Each time you bumped into a wall, you’d lose something from your bags. Specifically, relatively high-electronic energy from photons runs the danger of being degraded to heat and transferring charge or excitations can get trapped by “defects.”

Newton said retirement has given him more freedom to indulge his intellectual obsessions, including theoretical chemistry and other fields — both scientific and non-scientific. He hasn’t had any urge to take refuge in fishing or golf.

“The beauty of today’s life is that retirement is whatever you want to make of it,” he said. “It’s much more common now to be active retired. For the last five years, I’m doing more or less than the same things as the first 40, due to the generosity of my department and my department head, Alex Harris.”

Raised in Boston, Newton, who prides himself on not having a regional accent, lives in Strongs Neck with his wife Natika, a philosopher who until last year was also a professor at Nassau Community College. In the fall, she will teach a course in the Osher Lifelong Learning Institute at Stony Brook.

His daughter, Erika Newton, is a staff physician at the Stony Brook Medical Center. Her husband, John Hover, is leader of the grid group at BNL, which is part of the Relativistic Heavy Ion Collider ATLAS computing facility.

Son Joel, who lives in Nyack, New York, is a guitarist who plays jazz and fusion with the Joel Newton Situation. The benefit of the collaboration between theoretical and applied chemistry becomes clearer over time.

“The interplay of theory and experiment is grist for historians and philosophers of science,” Newton said.

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Even when most electronics aren’t functioning or are in sleep mode, they consume power. Leaving an inactive laptop long enough without charging it causes the battery to drain.

That’s not the case, however, with a developing technology called spintronics. Researchers are developing ways to use the spin of particles to operate DVR devices, smart phones and space technologies.

“The hope with spintronics is that you save the state and you won’t consume energy,” explained Javier Pulecio, a research associate in physics at Brookhaven National Laboratory. “When you turn it on, it’s instantly on. It has everything saved in its current position.” It is, Pulecio explained, like a refrigerator magnet, which stays magnetized.

Spintronic technology is still in the early stages of development, said Pulecio, with some significant fundamental hurdles to overcome before it will have widespread application in consumer electronics. One of the challenges is figuring out how to transport an electron’s spin over a longer distance, enabling it to become a useful carrier of a signal.

If scientists put an electron with a particular spin through a copper wire, the approximate distance the spin will stay polarized (or in the same state it was in when it entered the wire) is about 2 nanometers. In a normal conductor, the electron scatters, which causes the spin to change state or “flip.”

For perspective, an inch is 25,400,000 nanometers. The distance for that signal is “really tiny,” Pulecio said. “Current transistor technology is much larger than that.”

One possible solution is graphene, which is pure, two-dimensional carbon that is one atom thick. Graphene enables an electron to stay polarized for longer distances — microns instead of nanometers. It allows electrons to move without scattering, an activity known as ballistic transport.

Pulecio recently led a team that published a paper in Nature Communications that described how they created nanodevices with magnetic vortices in them. The configuration of the vortex is like a hurricane. It has a core, like the eye of a storm, with a circular magnetization around the center, like the clouds circling the eye.

He used two discs of different thicknesses but similar diameter on top of one another. This created orbits of spinning electrons of different sizes.

Even though the two discs had orbits that wanted to move differently, they synchronized through strong interactions to create a new orbit size during the motion. The electrons from the disc with the smaller-sized orbit were pulled out to an orbit that was closer to the larger one.

Pulecio’s mentor Dario Arena, a physicist in the photon sciences directorate at BNL, described the results in this experiment as “very promising.”

While Pulecio is still “quite young by the standards in the field,” Arena said “colleagues from other institutions have commented on how impressed they are with his results.”

Pulecio is studying other magnetic quasiparticles, such as skyrmions, which could lead to a reduction of the energy necessary to excite them by six orders of magnitude (or by a million times). He is interested in trying to bridge the fundamental science to its application. He hopes to contribute to creating smaller, more energy-efficient devices.

Arena explained that spintronics has current applications.

“Spintronics is not an abstract curiosity in the lab,” Arena said. “It is the foundation underpinning our advanced hard drives on computers. Even as more and more personal computers are moving toward solid-state hard drives, magnetic hard disk drives are finding an even more important application in cloud-based services such as Netflix, Dropbox, iCloud and many others.”

Arena said spintronic devices are marketed by companies such as Freescale, a spinoff of Motorola. While it isn’t currently used in consumer electronics, spintronics has found application in “harsh” environments where traditional semiconductor memory may have deficiencies, he said.

A resident of Wading River, Pulecio and his wife Alexandra, who is a science educator at BNL, welcomed a son, Xavier John, to their family eight months ago.

Born in Chicago and raised in Tampa, Fla., Pulecio said he enjoys mountain biking and fishing in and around Long Island. Pulecio’s mother Catalina, who grew up in Colombia, came to the United States because she saw greater opportunities for her family.

She didn’t speak English well when she arrived and made considerable sacrifices, he said. For his siblings and him, it was never a question of if they were going to college, but when and where.

Pulecio said he appreciates the opportunities he has at BNL. “My group leader Yimei Zhu and mentor Dario Arena have provided me with amazing support and guidance,” he said. “Our ability to understand, alter and control material at the atomic level makes this a truly exciting time to be a scientist.”

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The scent of a skunk, the familiar face of a friend, or the sound of shattering glass become part of a code that makes each of these stimuli familiar and recognizable almost immediately with each subsequent experience.

Glenn Turner, an associate professor at Cold Spring Harbor Laboratory, explores how one of the research world’s favorite test subjects, the fruit fly, develops a memory for smells.

“We can use a bunch of different techniques to understand how neurons in a memory center respond to different smells,” he said. “One of the things we found is that those neurons have really specific responses.”

Neurons, or the wiring cells that carry signals and affect everything from telling muscles to move to processing thoughts or activities, have such a highly specific signature that Turner can “easily tell the difference between when a fly smells a grapefruit and when it smells a lime.”

There is not, however, a universal signal in the brain of every fly, rat, monkey, or dolphin for certain senses. Each creature has a unique response to a sensory cue.

Turner said this is akin to a human’s response to the odor of durian, a fruit that smells like sweat socks. To those people who eat the fruit, the smell is appealing because they like the taste. Many people, however, react to the scent in the same way they would if they walked into an airless locker room after an overtime basketball game.

Thomas Clandinin, an associate professor of neurobiology at Stanford School of Medicine, who has known Turner for over two decades, described Turner’s work as “highly innovative.” Turner is “widely credited with being one of the people who made it possible to monitor neural activity in the fly, an approach that has really revolutionized fly neuroscience.”

Clandinin credits Turner with being “very good at teaching people how to use his approaches, magnifying the community impact.”
Recently, Turner conducted experiments in which he looked at the patterns of activity in the memory center of the fly’s brain to see if he could tell the difference between the neural signature of bananas and of apples. The goal was to see if the patterns were stimulus-specific so that they could account for the accuracy with which flies form memories.

The perceptual whole is “greater than the sum of the parts,” Turner said.

Fluorescence microscopy makes a protein in a cell increase in brightness whenever it is active. He used that technique to express individual neurons in a region of the fly’s brain called the mushroom body, to see what components of a smell cause the fly to react and interpret that smell.

“We were able to show that different individual synaptic sites have different tuning properties,” Turner said. “The only time the mushroom body signaled to its downstream partners was when several inputs were active at the same time.”

Flies have several input sites that are waiting for a smell to come along that they can process and understand. If the majority of the parts of a smell are consistent, the fly will process the chemicals in the air as that scent. If not, however, the fly may not react.

Another step in his research, he said, could be to determine what neurological changes occur in response to some learned connection. If, for example, a fly often smells the noxious fumes of paint thinner when he eats, he might process that signal in a way that’s different from a fly that is looking for a more conventional smell in the search for food.

One of the reasons the fly is an appealing subject for these studies is that there are mutant versions that don’t form memories. By studying these mutants, researchers like Turner can compare the neurological circuit of a fly that recognizes the smell of a banana from one that can’t.

Turner and his wife Lorraine Lew, a nutritionist who works at a renal dialysis clinic, got married last November. Turner enjoys hiking behind the Cold Spring Harbor Laboratory library and biking.

As for his research, Turner hopes his basic understanding of the way a fly interprets the information around it will have applications to other creatures.

“I would hope that one day, we will get a more concrete understanding of learning and memory,” he said.

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He creates materials that build themselves. By attaching parts that will connect in a specific way, he can build something that could be useful in fields ranging from harvesting energy, to advancing medical technology to offering clearer views in basic research.

Oleg Gang, a group leader in soft and bio-nanomaterials at the Center for Functional Nanomaterials at Brookhaven National Laboratory, is at the forefront of a field where the materials he’s trying to construct are about 1/1000th the width of a human hair.
At incredibly small scales, matter behaves in ways that are different from the world of apples falling from trees, cars slowing down on snowy roads, or baseballs flying over fences. Going from atoms to molecules to nanoparticles to large objects causes matter to change its properties due to the collective effects between atoms and the relative surface contribution, Gang explained.

Gang has been using something from another area of science for these self-assembled materials: DNA. The genetic blueprint that determines whether a cell becomes a part of a snail, a snake or a salmon has matching base pairs that make it a good candidate for construction. By attaching these DNA shells to small objects, Gang can encourage the pieces to come together on their own, as combinations of base pairs seek each other out, the way puzzle pieces floating in a dish might if they had a sequence of attachments that lined up in a specific order.

Extending the puzzle analogy, Gang has been able to put together two-dimensional structures. One of the many challenges facing him and others at Brookhaven, Harvard, Northwestern and a handful of other groups with similar research goals is figuring out how to generate three-dimensional structures.

Gang’s colleagues describe him as an innovator.

“The concepts he and a small number of other groups are pursuing represent an entirely new approach to constructing materials,” said Charles Black, a group leader in materials synthesis and characterization at the CFN. Gang is considered “an excellent scientist, making breakthrough discoveries while remaining careful in his work and sure of his scientific claims.”

Gang, who has several patents awarded with others pending, studies the basics of these self-assembly processes, hoping to understand more about how to build structures with more complex architecture.
He also takes requests from other scientists, who are looking to improve on existing products or who want to tap into his expertise to refine a product they already use.

He started his work with gold, but has now expanded to other classes of nanoparticles, including magnetic, catalytic, fluorescent and metallic.

Gang said he has helped improve various properties through self assembly. A few years ago, he said, he raised the light-emitting ability of a nanoparticle by a factor of five. That, he said, might prove useful in biodetection.

He also published results where he improved the ability of a detector to find the chirality, or spin, of particles, by a factor of 100.
Gang is developing research that will enable the structures he creates to transform to something else.

“A structure is the result of a particular interaction,” he said. “As soon as we change how the particles interact — they are not happy and are trying to find another configuration — they will change into something different.”

Gang said he benefits from working at the 7-year-old Center for Functional Nanomaterials, where he can not only work with a team of faculty fluent in the world of nanoscience, but where he can also collect additional information at the National Synchrotron Light Source and from electron microscopes.

Science, Gang said, often benefits by imitating nature. A plane, for example, isn’t a bird, although both can fly.

Gang believes his work is not at the early Leonardo DaVinci stage of flight, but is rather closer to the Wright Brothers, where he and other scientists can lift the plane off the ground, but can’t fly it yet.

Gang, who grew up in the western part of the Ukraine and then moved to Israel, now lives in Setauket with his wife, Alina, who works for a biodetection company in Medford. The couple’s 19-year-old daughter, Danielle is studying creative writing at SUNY Potsdam. They also have a 15-year-old son, Gabriel.

As for his work, Gang is excited about the prospects for contributing to science and society.

“We’re in a situation where many types of things become possible,” he said.

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It starts with a question and a possible explanation. From there, the leader tests to see whether he or she was right. If the initial information suggests the original possibility was accurate, the leader runs several other tests to confirm the result.

Scientists and researchers follow that formula to crack nature’s code. They tend to get excited when, for example, they find a certain gene appears to be involved in a particular disease. Researchers can be as disappointed as little league ballplayers after losing a close game if they find no such connection.

Jesse Gillis, an assistant professor of computational genomics at Cold Spring Harbor Laboratory, however, thinks many of those so-called negative results can be as constructive as finding positive ones. “Negative results are so valuable,” he said. Negative results help scientists understand all the available information and not just the usual suspects, especially in genetic disorders.

Often, tests for the role of key genes in diseases come up with some candidates almost every time, like P53, he said. P53 is a tumor suppressor gene, which means that, when it functions correctly, it prevents cells from developing into potentially deadly tumors. When other genes have some connection to a disease, they are often related to a gene like P53.

The interpretation of results is dominated by genes for which scientists already have considerable amounts of information. The interpretation of what is going on with numerous genes tends to be dominated by several important genes.

Gillis works in a field of computational biology in which researchers are looking for combinations of genes, RNA, and proteins that all could play a role in a disease. He studies a scientific field called “guilt by association,” in which combinations of mutations, signals, or defects might increase the likelihood of developing a complicated disorder, in which people with similar symptoms have a range of genetic differences.

He uses guilt by association to understand the combination of mutations which might increase the likelihood of developing a disorder like schizophrenia or autism.

Gillis hopes to be able to look closely into what these genes have in common to “be able to say when we have false positives.” In his opinion, attempts to give comprehensive lists of the genes causing complex disorders could produce false positives that could be as high as 50 percent. He says there is something of a specificity problem, where the overlaps among genes that might have a connection to schizophrenia are not specific enough.

Before he came to CSHL, Gillis conducted post-doctoral research in the laboratory of Paul Pavlidis, an associate professor at the University of British Columbia. Gillis impressed his former lab director. Gillis is “super-smart, serious and [a] skeptical scientist who is not afraid to question deep assumptions in our field,” Pavlidis offered.

Gillis said the notion of guilt by association is an older idea. Scaling that up to apply it to expressing a disease goes back to around the turn of the millennium, when scientists started applying computational principals to these data ranges.

Where Gillis hopes to make a difference is finding something meaningful to say based on the data, instead of echoing other findings.

Gillis, who grew up in Toronto, said he “always liked messy data.” He was not as excited by the typical experiment where scientists tested one hypothesis and the results either worked or they didn’t. He enjoyed studying data-driven discovery, where he could look at a combination of data that was diverse and potentially challenging to understand and interpret.

Gillis’s scientific curiosity is, in part, a product of his childhood environment. His father is a math professor, while his mother started her doctorate in developmental psychology by watching him play as a child.

Most of his American experiences have been on Long Island. He has been so busy setting up his lab — he arrived a year and a half ago — that he hasn’t had many opportunities to pursue his penchant for sailing.

Gillis hopes to have more data to work with in the coming years. “If I say genes are likely to have a property x or this set of genes is likely to have a property x, it matters how prevalent that property is,” he said. “If a gene is always important” then finding it has a role in a disease doesn’t “validate the reason it’s important in this context.”

The negative result might tell scientists more because “the gene not showing up is the more unusual finding.”

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Their world stretches from the treetops of Madagascar to the rain forests of Brazil to the salmon feeding grounds of bears in Alaska.

They study a wide range of animals, at the same time that they dedicate their work to the survival of species with uncertain futures.

Russell Mittermeier, Carl Safina, and Patricia Wright not only share a connection to Stony Brook University and to conservation, but they are also three of six finalists for the biennial Indianapolis Prize, considered the top award for the world’s conservationists. The award, which is administered by the Indianapolis Zoo, considers conservation candidates from all over the world. The winner, who will receive the Eli Lilly Medal and a $250,000 prize, will be announced on May 13.

“I am very proud of these outstanding members of our faculty,” SBU President Stanley said through an emailed statement to the Times Beacon Record Newspapers.

The three finalists recently attended an Earth Day tweet-up at the Student Activity Center at Stony Brook, where they shared their views on the prize, on conservation, and on the Long Island ecosystem. It was the first-ever Tweet-Up for the University. Members of the school, including Stanley and representatives from the Indianapolis Zoo, attended the discussion.

“Having three of the six finalists from Stony Brook speaks to the institution’s tradition of academic excellence and commitment to field work that positively impacts genuine conservation,” Rob Shumaker, the vice president of Conservation & Life Sciences at the Indianapolis Zoo, said after the meeting.

On the positive side, the tweeting trio talked of a comeback for a bird of national symbolic importance that hasn’t nested on Long Island since Dwight Eisenhower was president.

“Here on Long Island, for the first time in 60 years, we have a nesting pair of bald eagles,” said Safina. The head of the Blue Ocean Institute, Safina has written six books on threats facing the world’s habitats.

One of the strongest pieces of advice each of the Stony Brook finalists offered is to see animals in their natural habitat.

“Once you get out there, you’re connected for life,” Mittermeier, a leading field biologist who is also the president of Conservation International, told a combination of about 200 people in attendance at the SAC and those gathered in a virtual crowd through Twitter.

“Visiting places is not a trivial part of the fight for wildlife conservation,” Safina echoed.

Indeed, in 2012, Stony Brook inaugurated a new research, education and conservation building on the boundary of Ranomafana National Park in Madagascar called NamanaBe Hall. Stanley attended the inauguration, along with dignitaries from Madagascar.

The university president agreed that the experience of seeing these animals in the wild brings a new perspective.

“Observing [creatures] in their natural habitat brings a completely new level of awareness and appreciation for them and it is an extraordinary experience,” Stanley said.

Wright, who has studied lemurs for over a quarter of a century, was recently featured in an Imax movie narrated by Morgan Freeman called “Island of Lemurs: Madagascar.” The film, which Wright has seen 16 times and includes footage of lemurs on that island, shows the interactions of lemur social groups. Back in her office after the tweet up, Wright shared a chart that tracks how one female lemur leader lost her role in a “hostile takeover,” only to assume the same position with another group.

Wright, who helped establish Ranomafana National Park in 1991, calls the lemurs “her family,” along with her daughter and her well-traveled graduate students who have been to Madagascar and Peru.

Mittermeier, meanwhile, discussed how conservation groups are looking to turn the 2016 Olympic spotlight for host city Rio de Janeiro on some of Brazil’s conservation efforts.

Conservation International is joining other groups to suggest that the mascot could either be the muriqui or the golden lion tamarin. The muriqui, which weighs between 10 and 20 pounds, is an endangered monkey that is found only in the Atlantic coast forests of Brazil. Mittermeier also is urging the Olympics to use the tamarin, a monkey with reddish brown hair around its head and face that is considered a conservation success story, as an image on gold medals.

While he won’t likely be making an appearance in Brazil, Stony Brook’s own mascot Wolfie prowled around the ballroom during the Earth Day Tweet-Up.

Stony Brook officials said they were pleased with their first-ever tweet up and are interested in hosting this type of event again. The talented trio said it would be an honor to win the prize and that it underscores the appreciation for the value of their work.

As for why conservation is important, Safina explained, “it’s about trying to be human without ruining the world.”

Wright said she felt she “couldn’t be a person if she let all these animals go extinct.”

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Ivan Iossifov is using computer programs to try to understand the genetic piece of the autism puzzle. An assistant professor at Cold Spring Harbor Laboratory, Iossifov is comparing the genome of people with autism with the sequences from their unaffected siblings.

Iossifov explores areas of the genome where mutations might increase the risk of autism. He is searching for a “list of genes that, when you take it, can lead to autism directly or can increase the risk of a child being autistic,” he said. “Some genes are frequently mutated in autism.”

He can approach this mission by looking at “every nucleotide in each parent and each sibling,” he said. “We can zoom in on very particular genes.”

Historically, he said, genetic technology first allowed scientists to look for large-scale copy-number events, where a sequence of DNA might be repeated more frequently for one group of people than for another. As genetic sequencing has matured, however, he has been able to focus on nucleotide-level genetic variants, such as single base-pair substitutions.

“The new-generation sequencing technology becomes cheaper and faster amazingly quickly,” he said. “That does allow us to perform research that was unfeasible even five years ago.”

Iossifov said the research he’s conducting may help doctors and scientists understand some of the genetic components of autism. So far, his research shows that early genetic-based diagnosis is difficult. He estimates that he needs about ten times more genetic data in families before genetic-based diagnoses can become useful. While he said he is not an expert in autism, he said he strongly believes “that the earlier a child can be reliably diagnosed, the better.”

More broadly, Iossifov is interested in a large scope of neurodevelopment disorders as well as cancer. In the last few years, however, he’s focused considerable effort and attention on autism.
Autism, he explained, seems to require the kind of approach he has to research, looking at the big picture and narrowing that down to individual genes or even base pairs. So far, he has looked at the 1 percent of the nucleotides in the human genome that encode genes.

“We have been carefully examining each variant for its potential effect on the gene it belongs to,” he said. “We analyze thousands of families, focusing in on de novo variants,” variants present in a child and not in her parents.

Iossifov is now planning to extend his analysis over the complete genome. He is hoping to hire new staff before long, to help with data collection and analysis.

Iossifov is grateful for the backing of the Simons Foundation, which provided funding and supported the collection of many of the genetic samples he is studying. He hopes the foundation will continue to endorse efforts to scrutinize additional areas of the genome, even those that other scientists hadn’t previously considered, to find other regions where he might discover “interesting variants.”

Iossifov splits his time between Philadelphia, where his wife Ani Nenkova works in the Department of Computer and Information Science at the University of Pennsylvania, and Long Island. The couple have a four-year old son Pascal, whom they call “Paco.”
When he’s on Long Island, he enjoys visiting beaches. Iossifov said he speaks “one and a half” languages, although, at this point, he’s not sure which is the half. He grew up speaking Bulgarian, but his friends at home suggest he’s developed an American accent in his native tongue. “I apparently sound funny” speaking Bulgarian, he said.

Iossifov said his parents didn’t push him to do anything in particular, although he is following somewhat in the footsteps of his father, who is a retired chemist.

In terms of teaching their son about the world, Iossifov and Nenkova encourage him to understand that “he can go deeper,” in whatever he learns.

Iossifov is excited to continue working with autism. “Autism is a complex disorder and is highly prevalent. Any progress on autism would be great on many aspects.”