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Power of 3

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0 1888
Wellington Rody. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

Straightening teeth involves moving, changing and reconfiguring the bone and the gums that hold those teeth in place. While the gums and bone adapt to the suddenly straight teeth, the roots may encounter unusual stress that makes them more prone to deterioration.

That’s not particularly welcome news for hormone-riddled teenagers who are maneuvering through the minefield of adolescence with a mouth full of metal. Fortunately, however, significant root damage that threatens the health and stability of teeth occurs in only about 5 percent of the cases of people with braces.

Wellington Rody. Photo by John Griffin/Stony Brook University

The challenge for people whose roots resorb in response to orthodonture is that most patients don’t show signs of problems until the process is well under way.

Wellington Rody Jr., the chair of the Department of Orthodontics and Pediatric Dentistry at the Stony Brook University School of Dental Medicine, hopes to change that.

Rody, who joined the staff at Stony Brook last May, received a $319,000 grant from the National Institute of Dental and Craniofacial Research to find biomarkers that may show early signs of periodontal disease and dental resorption.

Rody explained that he is “searching for noninvasive markers of root destruction.” Once orthodontists start moving teeth around, a major side effect can be that roots are compromised, to varying degrees. It’s a “common side effect with everybody that wears braces,” but it is usually minor with no clinical relevance.

Currently, the only way to discover root destruction from braces is through X-rays or CT images. “The problem is that when we find those things, as a clinical orthodontist, sometimes, it’s already too late,” Rody said.

Since biomarkers of bone destruction and root destruction may overlap, the focus of his research is to search for biomarkers that can differentiate between the two processes and find the markers that are more specific to root destruction. A few biomarkers of root destruction have been proposed, but there aren’t enough studies to validate those markers. 

Rody will be searching for markers in both saliva and gum fluid. He anticipates that a panel of biomarkers may be more successful than trying to focus on one marker only.

If the markers, which Rody has been developing in collaboration with Shannon Holliday, at the Department of Orthodontics at the University of Florida, and Luciana Shaddox, from the Department of Periodontology at the University of Kentucky, are effective, they will likely provide guidance to clinicians so that high-risk patients may have their treatment plan adapted to prevent further damage.

The type of molecules Rody is searching for include proteins, lipids, metabolites and RNAs. He has been using proteomics, but in this NIH grant, he received enough funding to extend the analysis to other molecules.

According to Rody, there are many predisposing factors for bone loss in the literature. Predisposing factors for root destruction in the dentition also exist but are not well validated.“Genetics definitely plays a major role,” but as far as he is concerned “there is not genetic testing that is 100 percent reliable.”

Until he discovers a reliable biomarker, Rody, who maintains a clinical practice at Stony Brook about one and a half days a week, suggests taking follow-up X-rays after initiating orthodontic treatment, to make sure the “roots are behaving properly,” he said.

A patient who develops serious root destruction may need active monitoring. If the resorption is severe enough, orthodontists typically recommend stopping treatment for a period of one to five months, which is called a “holiday,” and then resume treatment. 

Wellington Rody on vacation in California with his family. Photo from W. Rody

It is only recommended if the patient shows signs of moderate or severe root destruction. Another option is to interrupt treatment early and accept some compromises in the final results 

“We try to get the patient out of braces as soon as possible” in cases of severe root resorption, Rody explained.

Rody has been working in this area since 2014. He received initial funding from the American Association of Orthodontists Foundation. He started by simulating bone and root destruction in a lab and looking for different molecular signatures between the two processes and has already published articles that highlight these differences.

The current NIH study will allow for the search for potential biomarkers. If the group finds them, the next step would be to try to validate them through a process that is expensive and requires large trials.

Ultimately, if and when he finds those biomarkers, Rody said he can use them in a noninvasive way to closely monitor a patient with periodic X-rays. He also might adjust the treatment regime to make sure the patient receives positive results without compromising the prognosis for his or her teeth in the longer term.

Rody believes orthodontics are worth the risk of root resorption, as patients who develop this side effect will likely keep their teeth for many years if not for their whole lives, even with some reduction in their roots.

“Considering all the benefits that orthodontic treatment can bring, in terms of function and cosmetics, it’s still justifiable” but the patient and his or her parents need to understand the risks and benefits associated with braces, he said. 

The teeth that are typically affected by root resorption are the upper front teeth.

Originally from Vitória in Brazil, which is six hours by car north of Rio de Janeiro, Rody lives in Port Jefferson with his wife, Daniela, and their 14-year-old daughter, Thais. 

As for his research, Rody explained that a major goal is to “detect the process [of root resorption] before it becomes severe.” If he does, he will be able to “revise the course of treatment and make sure we don’t allow destruction” of roots and the potential consequences for teeth to reach a high level.

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0 2009
Maureen O’Leary wraps fossils during an expedition in Mali. Photo by Eric Roberts

By Daniel Dunaief

Mali is filled with challenges, from its scorching hot 125 degree temperatures, to its sudden rainstorms, to its dangers from militant and terrorist-sponsored groups.

The current environment in the landlocked country in West Africa makes it extraordinarily difficult to explore the past in a region that includes parts of the Sahara Desert, but that, at one point millions of years ago, was part of a waterway called the Trans-Saharan Seaway.

Maureen O’Leary, professor of anatomical sciences at the Renaissance School of Medicine at Stony Brook University, led three expeditions to Mali, in 1999, 2003 and 2008, collecting a wide array of fossils and geological samples from areas that transitioned from an inland seaway that was about 50 meters deep on average to its current condition as a desiccated desert.

Maureen O’Leary and Eric Roberts with Mali guards. Photo from Maureen O’Leary

On her third trip, O’Leary quickly left because she decided the trip was too dangerous for her and the scientific team. Rather than rue the lack of ongoing access to the region, however, O’Leary pulled together an international team of researchers from Australia, the United States and Mali to look more closely and categorize the information the research teams had already collected from the region.

“We made the most of a bad situation,” O’Leary said. “It is a silver lining, to some degree.”

Indeed, O’Leary and her collaborators put together a paper for the June 28 issue of the Bulletin of the American Museum of Natural History that is over 170 pages and contains numerous images of fossils, as well as recreations of a compelling region during a period from 100 million to 50 million years ago. This time period coincided with one of the five great prehistoric extinction events, during the Cretaceous-Paleogene boundary.

O’Leary characterized some of the more exciting fossil finds from the region, which include the first reconstruction of ancient elephant relatives and large predators such as sharks, crocodiles and sea snakes.

The size of some of these creatures far exceeds their modern relatives. For example, O’Leary’s scientific colleagues estimate that a freshwater catfish was about 160 centimeters in length, which is four times the total size of a modern catfish. The larger catfish dovetails with similar observations the researchers had made about sea snakes in 2016 and 2017. They started to knit this trend into a preliminary hypothesis in which a phenomenon known as island gigantism may have played a role in selecting for these unusually large creatures.

“Species become bigger in these environments,” O’Leary said, suggesting that other scientists have made similar observations. “It’s not clear what causes that kind of selection.”

Above, some of the species that lived in and around the TransSaharan Seaway, including an extinct species of crocodile. Illustrated by Lucille Betti-Nash/ Department of Anatomical Sciences, Stony Brook University.

 

In addition to studying vertebrate and invertebrate fossils, scientists including Eric Roberts at James Cook University in Australia looked at the geology of the region. Roberts helped name and describe many of the formations in the area. This provides context for the lives of creatures who survived in an environment distinctly different from the modern milieu of the Sahara Desert.

Roberts, who is a part of the Sedimentary Geology & Paleontology Research Group that has nicknamed themselves Gravelmonkeys, explained that his initial efforts in Mali came from the fieldwork over a course of weeks when he explored the rock sequences and took copious notes on them.

He suggested that the region still represents a geoscience frontier, in part because it is so difficult to get to, takes serious logistics to do fieldwork and is hard to maintain research.“Over many years, I have worked with collaborators on the project to analyze the samples in many different ways and especially to compare our notes and analytical results with descriptions of rocks and geological formations in other parts of the Sahara and further afield in Africa to understand how they are different and how they correlate,” he said.

O’Leary suggested that the paper provides some context for climate and sea level changes that can and have occurred. During the period she studied, the Earth was considerably warmer, with over 40 percent of today’s exposed land covered by water. Sea levels were about 300 meters higher than current levels, although the Earth wasn’t home to billions of humans yet or to many of the modern day species that share the planet’s resources.

Robert Voss, the editor-in-chief of the series at the American Museum of Natural History, praised the work for its breadth. “This was an unusually large and multidisciplinary author team, as appropriate for the broad scope of the report,” he explained .

“Seldom is such a large geographic area so poorly known paleontologically, so there was a unique opportunity here to break new ground and establish a broad framework for future work,” he added.

Voss described O’Leary as a “force of nature” who “responds constructively to peer reviews.” Roberts, too, appreciated the effort O’Leary put into this work.

O’Leary “drove the entire process and product,” which was only possible with someone of her “vision to wrangle so much science from so many different scientists into one place,” he offered in an email.

Roberts is very pleased with the finished product and added that it is “something that I will be proud of for the rest of my career. This took a lot of effort over the years and it great to see the end product.”

O’Leary said that much of the literature for the science in Mali was in French, which had kept it a bit below the radar for scientific discourse, which tends to be in English.

Indeed, O’Leary was able to facilitate conversations among the many people involved in this project because French was the common denominator language. She studied French at the Holton-Arms School in Bethesda, Maryland. “When I was sitting in my high school French class, I didn’t think it would come in so handy to be fluent in French” in her career, O’Leary said. “It was helpful as a female leader in this situation to be able to speak for [myself], whether speaking to other Americans or collaborating or working with guards.”

O’Leary plans to look at different projects in the United States, including in Puerto Rico, and in Saudi Arabia next. “We now have this synthetic story for Mali [and will be] building out from this to other areas. I anticipate a large time to ramp up to study areas like deposits in Nevada.”

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Gábor Balázsi. Photo from SBU

By Daniel Dunaief

Take two identical twins with the same builds, skill sets and determination. One of them may become a multimillionaire, a household name and the face of a franchise, while the other may toil away at the sport for a few years until deciding to pursue other interests.

What causes the paths of these two potential megastars to diverge?

Gábor Balázsi, an associate professor in biomedical engineering at Stony Brook University, asked a similar question about a cellular circuit in the hopes of learning more about cancer. He wanted to know what is it about the heterogeneity of a cancer cell that makes one susceptible to treatment from chemotherapeutic drugs and the other resistant to them. Heterogeneity comes from molecular differences where the original causes may be subtle, such as two molecules colliding or a cell being closer to the tumor’s surface, while the consequences can create significant differences, even among cells with the same genes.

In research published this week in the journal Nature Communications, Balázsi used two mammalian cell lines that were identical except that each carried a different synthetic gene circuit that made one more heterogeneous than the other. He subjected the two cell lines, which would otherwise perform the same function, to various levels of the same drug to determine what might cause one to be treatable and the other to become resistant. 

Through these mammalian cells, Balázsi created two circuits, one of which kept the differences between the cells low, while the other caused larger differences. Once inserted in the cell, these gene circuits created uniform and variable populations that could serve as models for low and high heterogeneity in cancer.

Working with Kevin Farquhar, who recently graduated from Balázsi’s lab, and former Stony Brook postdoc Daniel Charlebois, who is currently at the Department of Physics at the University of Alberta, Balázsi tried to test how uniform versus heterogeneous cell populations respond to treatment with different drug levels. 

Using the two synthetic gene circuits in separate but identical cell lines, the Stony Brook scientists, with financial support from the National Institutes of Health and the Laufer Center for Physical and Quantitative Biology at SBU, could re-create high and low stochasticity, or noise, in drug resistance in two cell lines that were otherwise identical.

While the work is in its preliminary stages and is a long way from the complicated collection of genes responsible for various types of cancer, this kind of analysis can test the importance of specific processes for drug resistance.

“Only in the last decade or so have we come to realize how much heterogeneity (genetic and nongenetic differences) can exist within a tumor in a single patient,” Patricia Thompson-Carino, a professor in the Department of Pathology at the Renaissance School of Medicine at SBU, explained in an email. “Thinking of cancer in a single patient as several different diseases is a bit daunting, though currently, this heterogeneity and its direct effects on how the cancer behaves remains poorly understood.”

Indeed, Thompson-Carino added that she believes Balázsi’s work will “shed light on cancer cell responses to therapy. With the rise in cancer therapies designed to specific targets and the resistance that emerges in patients on these therapies, I think [Balázsi’s] work is of extremely high value” which may help with the puzzle of how nongenetic or epigenetic heterogeneity affects responses to treatment, she continued.

In the future, researchers and clinicians may look to develop new ways of biomarker analysis that considers the variability, rather than just the average level of a biomarker.

Balázsi suggested that looking only at the variability of cells is analogous to observing an iron block sinking in water. Someone might conclude that all solids sink in liquids. Similarly, scientists might decide that cellular variability always promotes drug resistance from observations when this happens. To gain a fuller understanding of the effect of variability, however, researchers need to equalize the averages. They then need to explore what happens at various levels of drug treatment.

Current therapies do not target heterogeneity. If such future treatments existed, doctors and scientists could combine ways of treating heterogeneity with attacking cancer, which might work in the short term or prevent cancer from recurring.

Balázsi suggests his paper is a part of his attempt to address three different areas. First, he’d like to figure out how to categorize patients better, including the variability of biomarkers. Second, he believes this kind of analysis will assist in creating future combinations of treatments. By understanding how the variability of cancer cells contributes to its reaction to therapies, he might help create a cocktail of treatments, akin to the effort that helped with the treatment of HIV in the lab.

Third, he’d like to obtain cancer samples and allow them to evolve in a lab, where he can check to see how they respond to treatment levels and administration scheduling. This effort could allow him to determine the optimal drug combination and dosing for a patient.

For the work that led to the current Nature Communications paper, Balázsi explored how mammalian cells respond to various concentrations of a drug. Over 80 percent of the genes in these cells are also present in human cells, so the mechanisms he discovered and conclusions he draws should apply to human cancer cells as well.

He concluded that cells with more heterogeneity, where the cells deviate more from the average, resist drugs better when the drug level is high. These same cells, show greater sensitivity when the drug is low.

Balázsi recognizes that the work he’s exploring is a “complex problem” and that it requires considerable additional research to understand and appreciate how a therapy might kill one cancer cell, while the same treatment in the same environment doesn’t have the same effect on a genetically identical cell.

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0 1683
Ela Elyada. Photo by Giulia Biffi

By Daniel Dunaief

They have the ability to call the body’s armed forces. They may interact with the immunological foot soldiers and, then, somehow, inactivate them, allowing the destructive cancer they may aid and abet to continue causing havoc.

This is one hypothesis about how a newly discovered class of fibroblasts may play a role in the progression of pancreatic cancer.

Ela Elyada, a postdoctoral fellow in David Tuveson’s lab at Cold Spring Harbor Lab, partnered up with Associate Professor Paul Robson at the Jackson Laboratory in Farmington, Connecticut, to find a new class of fibroblast in pancreatic cancer.

This cell, which they called antigen-presenting cancer-associated fibroblasts (or apCAFs) had the same kind of genes that are usually found in immune cells. Cells with these genes have signals on their surface that present antigens, or foreign parts of viruses and bacteria to helper T-cells. Elyada and Robson showed that the apCAFs can use their immune cell genes to present peptides to helper T-cells.

With the apCAFs, the researchers hypothesize that something about the immunological process goes awry, as the T-cells show up but don’t engage.

Elyada and Robson suspect that the activation process may be incomplete, which prevents the body’s own defense system from recognizing and attacking the unwelcome cancer cells.

While she was excited about the potential of finding a different type of cell, Elyada needed to convince herself, and the rest of the scientific community, that what she’d found was truly original, as opposed to a scientific mirage.

“We spent hours and hours trying to understand what is different in this type of cell,” Elyada said. “Like everything new you find, as a scientist, you really question yourself, ‘Is it real? Is it an artifact of the single cell?’ It was really important for me to do everything I could from every angle to make sure they were not macrophages that looked like fibroblasts or cancer cells that looked like fibroblasts.”

After considerable effort, Elyada was sure without a doubt that the group had found fibroblasts and that these specific cells, which typically are involved in connective tissue but which pancreatic cancer uses to form a shell around it, contained these immunological genes.

She sees these cells in different experiments from other people inside and outside the lab, which further supports her work and found the apCAFs in mice and human pancreatic ductal adenocarcinoma, which is the fourth leading cause of cancer-related deaths in the world.

The fibroblasts, which are not cancerous, play an unclear role in pancreatic cancer. 

Elyada explained that single-cell sequencing enables scientists to look at individual cells, instead of at a whole population of cells. Scientists “have started to utilize this method to look at differences between cells we thought were the same,” she said. “It’s useful for looking at the fibroblast population. Scientists have appreciated that there’s probably a lot of heterogeneity,” but they hadn’t been able to describe or define it as well without this technique.

The results of this research, which was a collaboration between Elyada, Robson and others, were recently published in the journal Cancer Discovery. Robson said it was a “great example of how [single-cell RNA sequencing] can be very useful in revealing new biology, in this case, a new subtype of cancer-associated fibroblast.”

Earlier work in the labs of Robson and Tuveson, among others, have shown heterogeneity within cancer-associated fibroblast populations. These often carry a worse prognosis.

“We are very interested in continuing to explore this heterogeneity across tumor types and expect we will continue to find new subtypes and, although we have yet to confirm, would expect to see other solid tumor types to contain apCAFs,” Robson said.

“We still need to work hard to reveal their function in the full animal, but if they turn out to be tricking the immune cells, they could be a target for different immune-related inhibition methods,” explained Elyada.

The newly described fibroblast cells may be sending a signal to the T-cells and then either trapping or deactivating them. Elyada and Robson both said these results, which they developed after working together since 2016, have led to numerous other questions. They want to know how they work, what the mechanisms are that allow their formation, what signals they trigger in T-cells and many other questions.

Elyada is working with Pasquale Laise in Andrea Califano’s lab at Columbia University to gather additional information that uses this single-cell sequencing data.

Laise has “a unique way of analyzing [the information] to look at how the sequencing can predict if proteins are active or not active in a cell,” she said. Laise is able to predict the activity of transcription factors according to the expression level of their known target.

Elyada may be able to use this information to understand the source cell from which the fibroblasts are coming.

Originally from Israel, Elyada has been working as a postdoctoral researcher in Tuveson’s lab for about six years. She lives in Huntington Village with her husband Gal Nechooshtan, a postdoctoral researcher at Cold Spring Harbor Laboratory’s Woodbury complex. The couple has two daughters, Maayan, who is 10, and Yael, who is 8.

Elyada hopes to return to Israel next year, where she’d like to secure a job as a professor and build on the work she’s done at CSHL.“I definitely want to keep working on this. This would hopefully be a successful project in my future lab.”

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0 1976
Mircea Cotlet. Photo courtesy of BNL

By Daniel Dunaief

An innovative scientist in the world of nanostructures, Mircea Cotlet recently scored Inventor of the Year honors from Battelle.

A principal investigator and materials scientist in the Soft and Bio Nanomaterials Group at the Center for Functional Nanomaterials at Brookhaven National Laboratory, Cotlet has conducted a wide range of research over his dozen years on Long Island.

The distinction from Battelle, which manages BNL through Brookhaven Sciences Associates, honors researchers who have made significant scientific or engineering contributions that have societal or financial impacts.

“The award recognizes [Cotlet’s] ongoing contributions to materials science at BNL, specifically his work on low-dimensional semiconductors, 1-D nanowires, and tiny 0-D nanocrystals called quantum dots,” Katy Delaney, a Battelle spokesperson, explained in an email.

Researchers who have worked with Cotlet believe he deserves the honor.

Cotlet is an “extraordinary scientist” who “stands out” for his thorough work and creative approach” said Deep Jariwala, an assistant professor in the Department of Electrical and Systems Engineering at the University of Pennsylvania. Jariwala has known Cotlet for over two years and has collaborated with him over the last year.

Cotlet has “really laid the foundational ground in understanding the rules that govern charge and energy transfer across hybrid quantum confined materials systems that comprise quantum dots, organic molecules–two-dimensional materials as well as biologically photoactive materials,” Jariwala added.

The technologies will impact the science and technologies of sensing, displays and energy harvesting in the future, Jariwala predicted.

Eric Stach, a professor in the Department of Materials Science and Engineering at the University of Pennsylvania who had previously worked at the CFN, said Cotlet “tries to figure out ways of putting together disparate systems at the nanoscale.”

By combining these materials, Cotlet is able to “improve the overall performance” of systems, Stach continued. “He’s trying to tune the ability of a given material system to capture light and do something with it.”

Cotlet recently partnered self-assembled two-dimensional nanoparticles, such as the one-atom-thick graphene, with light-absorbing materials like organic compounds.

The result enhances their ability to detect light, which could be valuable in medical imaging, radiation detection and surveillance applications. The mini-partnership boosted the photoresponse of graphene by up to 600 percent by changing the structure of the polymer.

Indeed, a defense contractor has shown an interest in research they could use for low light level detection applications, Cotlet said.

Like other scientists at BNL, Cotlet not only conducts his own research, but he also helps other scientists who come to the Department of Energy facility to use the equipment at the CFN, to make basic and translational science discoveries.

Cotlet patented a self-assembly process before he published it.

He is continuing conversations with a big company that is exploring the benefits of this type of approach for one of its product, while he is also working with the technology transfer office at BNL to look at the development of photodetectors for low light applications.

“Having graphene and the conductor polymer would absorb light from ultraviolet to visible light,” Cotlet said.

The physics changes from bulk to nanoparticles to nanocrystals, Cotlet said, and he engineers the smaller materials for a given function.

“We basically like to play with the interface between different types of nanomaterials,” he said. “We like to control the light-simulated process.”

Working at an energy department site, he also has experience with solar panels and with light-emitting diodes.

Jariwala described the science as extending to interfaces that also occur in nature, such as in photosynthesis and bioluminescence. “By combining techniques and materials that we have developed and looked at, we hope to answer fundamental mechanistic questions and provide insights into long-standing questions about biological energy conversion processes,” he wrote.

As far as some of the current materials he uses, Cotlet works on graphene and the transition metal dichalcogenides and he explores their potential application as quantum materials. He tries to look for emerging properties coming out of nanomaterials for various applications, but most of his efforts are in basic science.

Jariwala explained that he and Cotlet are seeking to understand the efficient transduction of energy in quantum sized systems when they are brought close to one another in an orderly fashion.

After his upbringing in Romania, where he attended college, Cotlet appreciated the opportunity to learn from one of the pioneering groups in the world in single-molecule microscopy at the Katholieke Universiteit Leuven in Belgium, where he studied for his doctorate.

He also did a fellowship at Harvard, where he worked on unique microscopy, and then went on to conduct postdoctoral work at Los Alamos National Laboratory, where he worked on protein folding and on optimal imaging methods.

Cotlet arrived at the CFN just as the facility was going online.

“The CFN went beyond its original promise for cutting edge science,” he said. The center has been, and he continues to hope it will be, the best place he could dream of to conduct research.

The postdoctoral researchers who have come through his lab have all been successful, either leading their own projects or joining commercial teams.

Up until he was 18, Cotlet wasn’t focused on science, but, rather, anticipated becoming a fighter pilot. He discovered, however, that he had a vision defect.

“All my childhood, I was set up to become a fighter pilot,” but the discovery of a condition called chromatopsy changed his plans.

A resident of Rocky Point, Cotlet lives with his wife, Ana Popovici, who is an administrative assistant at BNL, and their middle school daughter.

As for his future work, he is interested in building on the research into quantum materials.

“I’m looking forward to trying to integrate my research” into this arena, he said.

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0 2195
Fusheng Wang. Photo from SBU

By Daniel Dunaief

Long Island’s opioid-related use and poisoning, which nearly doubled from 2015 to 2016, was higher among lower income households in Nassau and Suffolk counties, according to a recent study in the American Journal of Preventive Medicine.

Looking at hospital codes throughout New York to gather specific data about medical problems caused by the overuse or addiction to painkillers, researchers including Fusheng Wang, an assistant professor in the Department of Biomedical Informatics at Stony Brook University, George Leibowitz, a professor in Stony Brook’s School of Social Welfare, and Elinor Schoenfeld, a research professor of preventive medicine at the Renaissance School of Medicine at Stony Brook, explored patterns that reveal details about the epidemic on Long Island.

“We want to know what the population groups are who get addicted or get poisoned and what are the regions we have to pay a lot of attention to,” Wang said. “We try to use lots of information to support these studies.”

Data from The Journal

The Stony Brook team, which received financial support from the National Science Foundation, explored over 7 years of hospital data from 2010 to 2016 in which seven different codes — all related to opioid problems — were reported.

During those years, the rates of opioid poisoning increased by 250 percent. In their report, the scientists urged a greater understanding and intervening at the community level, focusing on those most at risk.

Indeed, the ZIP codes that showed the greatest percentage of opioid poisoning came from communities with the lowest median home value, the greatest percentage of residents who completed high school and the lowest percentage of residents who achieved education beyond college, according to the study.

In Suffolk County, specifically, the highest quartile of opioid poisoning occurred in communities with lower median income.

Patients with opioid poisoning were typically younger and more often identified themselves as white. People battling the painkilling affliction in Suffolk County were more likely to use self-pay only and less likely to use Medicare.

In Suffolk County, the patients who had opioid poisoning also were concentrated along the western section, where population densities were higher than in other regions of the county.

The Stony Brook scientists suggested that the data are consistent with information presented by the Centers for Disease Control and Prevention, which has found significant increases in use by women, older adults and non-Hispanic whites.

“The observed trends are consistent with national statistics of higher opioid use among lower-income households,” the authors wrote in their study. Opioid prescribing among Medicare Part D recipients has risen 2.84 percent in the Empire State. The data on Long Island reflected the national trend among states with older residents.

“States with higher median population age consume more opioids per capita, suggesting that older adults consume more opioids,” the study suggested, citing a report last year from the American Journal of Preventive Medicine.

Nationally, between 21 to 29 percent of people prescribed opioids for pain misused them, according to the study, which cited other research. About 4 to 6 percent of people who misuse opioids then transition to heroin. Opioid costs, including treatment and criminal justice, have climbed to about $500 billion, up from $55.7 billion in 2007, according to a 2017 study in the journal Pain Physician.

The findings from the current study on Long Island, the authors suggest, are helping regional efforts to plan for and expand capacity to provide focused and targeted intervention where they are needed most.

Limited trained staff present challenges for the implementation of efforts like evidenced-based psychosocial programs such as the Vermont Hub and Spoke system.

The researchers suggest that the information about communities in need provides a critical first step in addressing provider shortages.

New York State cautioned that findings from this study may underreport the burden of opioid abuse and dependence, according to the study. To understand the extent of underreporting, the scientists suggest conducting similar studies in other states.

Scientists are increasingly looking to the field of informatics to analyze and interpret large data sets. The lower cost of computing, coupled with an abundance of available data, allows researchers to ask more detailed and specific questions in a shorter space of time.

Wang said this kind of information about the opioid crisis can provide those engaging in public policy with a specific understanding of the crisis. “People are not [generally] aware of the overall distribution” of opioid cases, Wang said. Each hospital only has its own data, while “we can provide a much more accurate” analysis, comparing each group.

Gathering the data from the hospitals took considerable time, he said. “We want to get information and push this to local administrations. We want to eventually support wide information for decision-making by the government.”

Wang credited his collaborators Leibowitz and Schoenfeld with making connections with local governments.

He became involved in this project because of contact he made with Stony Brook Hospital in 2016. Wang is also studying comorbidity: He’d like to know what other presenting symptoms, addictions or problems patients with opioid-related crises have when they visit the hospital. The next stage, he said, is to look at the effectiveness of different types of treatment.

A resident of Lake Grove, Wang believes he made the right decision to join Stony Brook. “I really enjoy my research here,” he said.

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0 1983
Brendan Boyce, center, with Xiangjiao Yi, left, and Jinbo Li, who are graduate students at the University of Rochester. Photo by Jianguo Tao.

By Daniel Dunaief

Chances are high you won’t see Dr. Brendan Boyce when you visit a doctor. You will, however, benefit from his presence at Stony Brook University Hospital and on Long Island if you have bone or soft tissue lesions and you need an expert pathologist to diagnose what might be happening in your body.

A professor at the University of Rochester for 20 years, the internationally renowned Boyce joined the Renaissance School of Medicine at SBU in November, splitting his time between Rochester and Long Island.

Dr. Ken Shroyer, the chair of the Department of Pathology, reached out to Boyce with an unusual bone tumor case last spring. After that discussion, the two considered the possibility of Boyce adding his bone and soft tissue pathology expertise to the growing department. Boyce was receptive to the idea, particularly because his daughter Jacqueline lives in Woodbury with two of his seven grandchildren.

For local patients, Boyce adds a relatively rare expertise that could shorten the time for a diagnosis and improve the ability for doctors to determine the best course of action during surgeries.

“While the patient is already undergoing a surgical procedure, the preliminary diagnosis can guide the process of the surgery,” said Shroyer. “That’s difficult to achieve if we are dependent on an outside consultant. It happens, more or less in real time, if Boyce can look at the slides as they are being prepared and while the patient is still on the operating table.”

Prior to Boyce’s arrival, Stony Brook functioned the same way most academic medical centers do around the country when it came to bone and soft tissue cancers or disorders.

“There are only a handful of soft tissue and bone surgical pathology subspecialists around the country,” Shroyer said. “There’s an insufficient number of such individuals to make it practical like this at every medical school in the country.”

Many of these cases are “rare” and most pathologists do not see enough cases to feel comfortable diagnosing them without help from an expert, Boyce explained.

Boyce “was recruited here to help this program at Stony Brook continue to grow,” Shroyer said. “He enhances the overall scope of the training we can provide to our pathology residents through his subspecialty expertise. Everything he does here is integrated with the educational mission” of the medical school.

While bone and soft tissue tumors are relatively rare compared to other common cancers, such as colorectal or breast cancer, they do occur often enough that Stony Brook has developed a practice to diagnose and treat them, which requires the support of experts in pathology. Stony Brook hired Dr. Fazel Khan a few years ago as the orthopedic surgeon to do this work.

“To establish a successful service, there needs to be a mechanism to financially support that service that’s not solely dependent on the number of cases provided,” Shroyer said.

Boyce’s recruitment was made possible by “investments from Stony Brook University Hospital and the School of Medicine, in addition to support from the Department of Orthopedics and Pathology.”

Shroyer was thrilled that Boyce brings not only his expertise but his deep and well-developed background to Stony Brook.

It was “important to me that he was not only a highly skilled surgical pathologist, but also was a physician scientist, which made him a very attractive recruit,” Shroyer said.

Indeed, while Boyce will provide pathology services to Stony Brook, he will continue to maintain a laboratory at the University of Rochester.

Boyce’s research is “focused on the molecular mechanisms that regulate the formation of osteoclasts and their activity,” Boyce said. He emphasizes the effects of pro-inflammatory cytokines and NF-Kappa B, which are transcription factors that relay cytokine signaling from the cell surface to the nucleus.

These factors drive osteoclast formation and activity in conditions affecting the skeleton, which include rheumatoid arthritis, postmenopausal and age-related osteoporosis and cancers affecting the skeleton.

Osteoclasts degrade bone, which carve out deformities or the equivalent of potholes in the bone, while osteoblasts help rebuild the bone, repaving the equivalent of the roads after the osteoclasts have cleared the path. There are over a million sites of bone remodeling in the normal human skeleton and the number of these increases in diseases.

Boyce has studied various aspects of how bone remodeling occurs and how it becomes disturbed in a variety of pathological settings by using animal models. He uses cellular and molecular biological techniques to answer these questions.

On behalf of Boyce and three other researchers, the University of Rochester Medical Center just finished licensing a compound to a company in China that he recently contacted, which will do animal studies that will test the toxicity of a treatment for myeloma.

At this point, Boyce is applying in July for another five-year grant from the National Institutes of Health for research in his Rochester lab. He hopes to renew another NIH grant next year, which he has for four years. After he renews that grant, he will continue writing up papers and studies with residents and collaborating on basic science at Stony Brook as well.

Boyce and his wife Ann, have three children and seven grandchildren. Originally from Scotland, Boyce has participated in Glasgow University Alumni activities in the United States, including in New York City, where he walked in this year’s Tartan Parade with his daughters and their children.

As for his work at Stony Brook, Boyce is enjoying the opportunity to contribute to the community.

“The setting and faculty are very nice and congenial and I’ve been made to feel welcome,” he said.

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Many of Madagascar’s iconic lemur species such as this black-and-white ruffed lemur are critically endangered. Photo by Daniel Burgas

By Daniel Dunaief

As a part of an ambitious reforestation plan announced in March, Madagascar’s newly elected president Andry Rajoelina explained that he wanted to change the way his nation off the southwest coast of the African continent was known, from the Red Island to the Green Island.

An international collection of scientists, including lemur expert and award-winning scientist Patricia Wright of Stony Brook University, recently weighed in on other ways Rajoelina can help conservation goals for the country through a five-step solution they outlined in the journal Nature Sustainability.

“We are all very concerned” about the fate of biodiversity in Madagascar, said Wright. “We know that only with a collaborative effort can we push things in the right direction.”

Madagascar, which has numerous species endemic to the island nation, including many of the lemurs Wright studies, is known as the island of red clay in part because deforestation has exposed much of the clay underlying the country. This clay has eroded into rivers, which have washed into the ocean.

“If you flew over the whole island, it would be very sad” because of all the exposed red clay from deforestation, Wright said.

She remains optimistic about Rajoelina’s goals and the potential for achieving them. The president “talked about going on the offensive and reforestation is one of his platforms,” she said. “It’s most important to reforest with endemic species,” as opposed to eucalyptus and pine.

Unlike in other countries, where politicians sometimes view conservation and economic development as forces pulling in opposite directions, Malagasy leaders acknowledge and recognize the benefit of preserving unique habitats that are home to the rare and threatened species of Madagascar.

“If you destroy all the forests, you destroy all the water and they will no longer be able to farm,” Wright said. “The natural wildlife and habitats are closely connected to their well-being. One of the biggest industries is ecotourism, which supports many industries on the ground. It’s not like there’s a line between people and wildlife.”

Indeed, the scientists acknowledge the importance of financial growth for the country that dovetails with their conservation goals.

“Conservation needs to contribute to, and not detract from, national efforts targeting economic development,” Julia Jones of Bangor University, in Wales, who led the study, said in a press release. “It must not make situations worse for the rural poor who are so often marginalized in decision making.”

The people of Madagascar have many of the same needs as those in other countries, as they seek jobs, health care, and good schooling, Wright said. “These families are closer to not having enough food to eat and they are much poorer if the natural resources are all destroyed.”

Concerned about the fate of biodiversity in Madagascar, Jones contacted Wright, who suggested the team enlist the help of Jonah Ratsimbazafy from the University of Antananarivo in Madagascar.

“It was just a matter of bringing together some of the key players in conservation for 20 years,” explained Wright.

The group generated a list of five priorities.

First on the list is tackling environmental crime. The scientists suggest using new technologies, including remote sensing and rapid DNA barcoding, to allow forest rangers and others to identify protected species. To improve this effort, however, the Ministry of Justice also needs to enhance the way it reacts to environmental crimes.

The researchers suggest prosecuting and fining those who traffic in rosewood or the critically endangered species for the pet trade. They see progress in this arena in the northeastern part of the island nation, where prosecutors have effectively charged some people who have sold rosewood.

Second, the group recommends investing in protected areas. The researchers urge greater investment in policy, legal and economic conditions that encourage additional investment in nature, which could include improving infrastructure to develop tourism around protected areas, payment for ecosystem services and debt for nature swaps.

Critically endangered species such as these ploughshare tortoises may be extinct in the wild within the next few years if illegal collection isn’t stopped. Photo by Chris Scarffe

Third, the scientists urge that major infrastructure developments limit the impact on biodiversity. The current environmental impact assessment law is over 20 years old and needs an update to require the use of environmental assessment. This component also includes a greater commitment to enforcement.

Fourth, the scientists suggest strengthening tenure rights for local people over natural resources. Most farmers can’t get certification for their land, which reduces the incentive for them to invest in settled agriculture and potentially exacerbates forest clearance. A review of tenure laws could help local landowners and biodiversity.

Finally, researchers recognize a growing crisis in fuel wood. They urge an investment in reforestation efforts, which could provide environmental and economic benefits.

While these steps are important for Rajoelina and the government in Madagascar, Wright suggests several ways Long Islanders can help. She urges school teachers to cover Madagascar in their classes. Teachers in the area who are interested in gathering information about the island nation can write to Wright at [email protected].

She also urges people to become involved through social media, which they can use to have fundraisers through organizations like PIVOT, an organization committed to improving health in developing nations like Madagascar and strongly encourages people to visit Madagascar, where they can enjoy the benefits of ecotourism.

Visitors to Madagascar would have the incredible opportunity to witness the varied biodiversity for themselves.“We have charismatic lemurs,” Wright said, although many of them are critically endangered. Even if they can’t travel that far, people can support students who wish to study abroad.

“I don’t think health and wildlife are separated,” Wright said. “The health of the people depends on us preserving natural resources.”

She is looking forward to the Annual Association for Tropical Biology and Conservation meeting in Antananarivo, Madagascar, from July 30 through August 3. “Hopefully, we will be going forward with the next step during or shortly after that meeting.”

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Bruce Stillman. Photo courtesy of CSHL

By Daniel Dunaief

Bruce Stillman, the president and CEO of Cold Spring Harbor Laboratory, was recently awarded the prestigious Canada Gairdner International Award for his contributions to research about the way DNA copies itself. The 60-year-old prize, which Stillman will receive in a ceremony in October and that he shares with his former postdoctoral fellow John Diffley, includes a financial award of $100,000 Canadian dollars that he can spend however he’d like.

A native Australian, Stillman, who has been at Cold Spring Harbor Laboratory since 1979, recently shared his thoughts about the award, research at the lab and his concerns about science in society with Times Beacon Record News Media. 

How does it feel winning the Gairdner Award?

It’s one of the most prestigious awards in the life sciences in the world and it’s certainly a great honor to win it and to join the list of spectacular scientists in the history of the award. There are some really fantastic scientists who I very much admire who have received this award.

How does it relate to the research you’ve conducted?

The field of DNA replication and chromosome inheritance was recognized. It is something I’ve devoted my entire career to. There are a lot of people that have made important contributions to this field. I’m pleased to be recognized with [Diffley] who was my former postdoc. [It’s validating] that the field was recognized.

Has CSH Laboratory been at the cutting edge of discoveries using the gene-editing tool CRISPR?

Cold Spring Harbor didn’t discover CRISPR. Like many institutions, we’ve been at the forefront of applying CRISPR and gene editing. The most spectacular application of that has been in the plant field. Zachary Lippman, Dave Jackson and Rob Martienssen are using genetic engineering to understand plant morphogenesis and development, thereby increasing the yield of fruit. Hopefully, this will be expanded into grains and have another green revolution.

CSHL has also been making strides in cancer research, particularly in Dave Tuveson’s lab, with organoids.

Organoids came out of people studying development. Hans Clevers [developed organoids] in the Netherlands … Tuveson is at the forefront of that. The full promise hasn’t been realized yet. From what I’ve seen, we are quite excited about the possibility of using organoids as a tool to get real feedback to patients. It is rapidly moving forward with the Lustgarten Foundation and with Northwell Health.

What are some of the other major initiatives at CSHL?

The laboratory’s investment about 10 or 15 years ago in understanding cognition in the brain has paid off enormously. Neuroscientists here are at the forefront of understanding cognition and how the brain does computation in complicated decisions. [Scientists are also] mapping circuits in the brain. It took a lot of investment and kind of the belief that studying rodent cognition could have an impact on human cognition, which was controversial when we started it here, but has paid out quite well. At the same time, we are studying cognitive dysfunction particularly in autism. 

Any other technological advances?

There’s been a real revolution in the field of structural biology… [Researchers] have the ability to look at single biological molecules in the electron microscope. It shoots electrons through a grid that has individual biological molecules. The revolution, which was done elsewhere by many people actually, led to the ability to get atomic resolution structures of macro molecular complexes. 

Cold Spring Harbor invested a lot of money, well over $10 million to build a facility and staff a facility to operate this new technology. I’ve been working on this area for about 12, 13 years now … Our structural biologists here in neuroscience, including neuroscientists Hiro Furukawa and Leemor Joshua-Tor have really helped introduce a lot of new biology into CSHL.

What are some of the newer efforts at the lab?

One of the big new initiatives we started is in the field of cancer. As you know by looking around, there’s an obesity epidemic in the Western world. We started a fairly large initiative, understanding the relationship between obesity and cancer and nutrition, and we’re not unique in this. We’re going to have some significant contributions in this area. 

Cancer cells and the tumor affect the whole body physiology. The most severe [consequence] is that advanced cancer patients lose weight through a process called cachexia. We hired [new staff] in this new initiative, renovated a historic building, the Demerec building at a fairly substantial expense, which was supported by New York State. 

What will CSHL researchers study related to obesity?

We’re absolutely going to be focusing on understanding mostly how obesity impacts cancer and the immune system, then how cancer impacts the whole body physiology. Hopefully, once we start to understand the circuits, [we] will be able to intervene. If we can control obesity, we will by logic reduce cancer impact.

What worries you about society?

What worries me is that there is a tendency in this country to ignore science in policy decisions … The number of people not getting vaccinated for measles is ridiculous. There is this kind of pervasive anti-science, anti-technology view that a lot of Americans have. They want the benefits of science and everything that can profit for them. 

There are certain groups of people who misuse data, deliberately abuse misinformation on science to promote agendas that are completely irrational. One of the worst is anti-vaccination. … We should as a society have severe penalties for those who choose to go that route. They shouldn’t send their children to schools, participate in public areas where they could spread a disease that effectively was controlled. Imagine if polio or tuberculosis came back?

How is the lab contributing to education?

People need to act like scientists. It’s one of the reasons we have the DNA Learning Center, to teach people to think like scientists. If 99.99 percent of the evidence suggests [something specific] and 0.01 percent suggest something [else], you have to wonder whether those very small and vocal minority are correct.

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Gordon Taylor with technician, Tatiana Zaliznyak. A Raman microspectrometer is pictured in the background. Photo by J. Griffin

By Daniel Dunaief

Something is happening in the Twilight Zone of the ocean, but it’s unclear exactly who is involved and how fast the process is occurring. 

Plants and animals are eating, living, defecating and dying above the so-called Twilight Zone and their bodies and waste are falling toward the bottom of the ocean. But most of that matter isn’t making it all the way to the ocean floor.

That’s where Gordon Taylor, a professor and director of the NAno-RAMAN Molecular Imaging Laboratory at the School of Marine & Atmospheric Sciences at Stony Brook University, comes in. 

Taylor and Professor Alexander Bochdansky of Old Dominion University recently received a $434,000 three-year grant to study the way microorganisms eat, process and convert organic carbon — i.e., carbon that’s a part of living organisms like plants, sea birds and whales — into inorganic carbon, which includes carbon dioxide, carbonate, bicarbonate and carbonic acid.

“The inorganic carbon moves back and forth among these four chemical species,” Taylor explained in an email. Understanding the rate at which carbonic acid builds up can and will help lead to a greater awareness of ways the ocean, which used to have a pH around 8.2 — which is slightly basic, as opposed to levels below the neutral 7— is becoming more acidic.

Above, incubators that Alexander Bochdansky has used in Bermuda. The ones Taylor and Bochdansky will analyze will be smaller than these, which won’t require such a large A-frame to deploy. Images courtesy of A. Bochdansky

They will start by deploying the traps at a single depth, about 985 feet, along the ocean off the coast of Virginia. “We are going to look at who the players are,” Bochdansky said. “There might be only a few key players that degrade this organic carbon. With [Taylor’s] great methods, we can measure the uptake rate in single microbes. This is really exciting.”

The Twilight Zone received its name because it is 650 to 3,300 feet below the surface of the water. Some faint light reaches the top of that zone, but most of that region, which includes creatures that use bioluminescence to attract or find prey, is pitch black.

“The directory of which inventories and fluxes decrease [is] still poorly understood,” Taylor said. “Animals eating the material is one mechanism and we don’t know how important that is compared to microbial decomposition or remineralization,” adding that the goal of this project is to “better define the role of microorganisms in returning carbon to the inorganic pool.”

Taylor is exploring this area with new tools that will allow a greater depth of understanding than previously possible. His group has developed new experimental approaches to apply Raman microspectrometry to this problem. The organisms they examine will include bacteria, fungi and protozoans.

Their experiment will explore which organisms are recycling organic carbon, how fast they are doing it and what factors control their activities. Through this approach, Taylor will be able to see these processes down to the level of a single cell as the instrument can identify organisms that have consumed the heavy isotope tracer.

The Raman microspectrometer uses an optical microscope with a laser and a Raman spectrometer. This tool will measure samples that are micrometers thick, which is smaller than the width of a human hair. The microspectrometer can obtain data from a 0.3-micrometer spot in a cell and he has even produced spectra from single viruses.

The scientists will place phytoplankton common to the region in incubators that Bochdansky developed. They will use a heavy carbon isotope, called carbon 13, that is easy to find through these experiments and see how rapidly microorganisms that colonize are incorporating the isotopically labeled carbon.

Taylor and Bochdansky received funding for the project through the Biological Oceanography Program at the National Science Foundation in the Directorate of Geosciences. Twice a year, the division makes open calls for proposals on any topic of interest to researchers. The scientists submit 15 pages of text that the NSF sends to peer reviewers. A panel meets to evaluate the reviews and ratings and decides which projects to fund.

Bochdansky and Taylor have been “acquainted for a long time and have shared similar interests,” Taylor said.

The carbon experiments in the Twilight Zone account for about a quarter of the work Taylor is doing in his lab. The other research also employs Raman microspectrometry. The United States only has one or two other facilities that do environmental research comparable to the one in Taylor’s lab at Stony Brook. Europe also has three such tools, which can look into single cells using lasers.

One of the other projects Taylor hopes to get funded involves studying the distribution of microplastics in the ocean. “The instrument I have is one of the best tools to look at microscopic plastic particles,” because it identifies the plastic polymer and its source, said Taylor, who is awaiting word on funding from the National Oceanic and Atmospheric Administration.

The other work involves exploring viruses that attack plankton.

“We are exploring Raman methods for early detection of viruses that attack plankton,” Taylor explained. Every organism in the ocean has at least one virus that has evolved to attack it.

As for his work on the Twilight Zone, Taylor said the area acts as a filter of sorts because less than 20 percent of the organic material entering at the top exits at the bottom.

Bochdansky added that these microbes are critical to processes that affect oceans and the planet.

“That’s something people often overlook,” Bochdansky said. “We can’t understand the ocean if we don’t understand it at the level or the scale that’s relevant to microbes.”

Bochdansky is thrilled to work with Taylor, who he’s known for years but will collaborate with for the first time on this project.

“In my lab, we have measured the turnover and release of carbon dioxide,” Bochdansky said. In Taylor’s lab, he measures “the actual feeding of microbial cells.”

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