Science & Technology

Annie Laurie W. Shroyer and Thomas Bilfinger

By Daniel Dunaief

Convenience can come at a cost, even in medicine. When it comes to a heart procedure called cardiac artery bypass surgery, that cost could make a difference in the outcome for the patient.

Annie Laurie W. Shroyer, vice chair for research and professor in the Department of Surgery at Stony Brook University School of Medicine, and Thomas Bilfinger, a professor of surgery in the Division of Cardiothoracic Surgery at SBU, found that the mortality and major morbidity rates were lower for patients of surgeons performing procedures at a single center compared to those performing procedures at more than one center. 

Among physicians who operated at two or more hospitals, these surgeons performed better at their home hospital than at a secondary center.

They’ve published their findings in the Annals of Thoracic Surgery. The Society of Thoracic Surgeons identified the article as the Continuing Medical Education article for the month. The article will provide a much more in-depth learning experience to a subgroup of the journal’s subscribers who seek Continuing Medical Education credits. This, Shroyer explained, will make it more likely that cardiac surgeons will read it thoroughly and discuss it.

“We believe that, based on the results, particularly complex coronary artery bypass grafting (CABG) procedures may have a better outcome at bigger institutions,” Bilfinger explained in an email. Mortality for these procedures overall in the United States is low and the analysis is about differences of a few tenths of a percent, which becomes statistically significant due to the low number.

The central issue, Bilfinger said, is whether “the mother ship does better or worse than the satellite. Decision making about centralizing versus a de-centralized approach seems to be less driven by outcomes and rather by business decisions in many circumstances. The study adds some subjective data to this discussion.”

Using a measure called observed-to-expected mortality ratios based on the health of the patient and risks of the procedure, the ratio for multicenter surgeons was higher for the satellite facilities compared to their home facilities. The ratios were 1.17 for surgeons operating at satellite facilities versus 1.01 for multicenter surgeons performing the procedure at their home hospital.

The volume of surgeries is a complicated issue, Bilfinger cautioned. “There are very well-performing smaller volume places throughout the country,” he explained in an email. “It involves dedication to the procedures from admission to discharge.”

Assuming the surgeon is just as effective in different hospitals, which is “open to discussion,” any observed difference could be attributable to the system, Bilfinger explained. Measuring the effectiveness of the participants in the process, including nurses, anesthesiologists and orderlies, is a question for ongoing research, he continued.

Joseph Carey, a cardiovascular and thoracic surgeon in Torrance, California, conducted a study based on information from California about a decade ago. In an email, Carey suggested that “you pay a price in quality working in unfamiliar conditions and I believe hospital managers do not want their surgeons traveling about.” He added that this paper “is an important reminder” of this.

Carey added that hospital systems and the makeup of the “heart team” may also be important to the outcome of a surgery.

Future research, which Shroyer plans to conduct, will evaluate other factors, such as patient risk, processes and structures of care, that impact cardiac surgical outcomes.

Other researchers could extend this study, which compares the quality of care for surgeons who work at single sites and multisites, to other areas of medical care, enabling hospital networks, insurance companies and patients to make informed risk-based decisions prior to approving difficult procedures.

The challenge, however, with similar studies for other conditions, is in finding national information. “This is the best documented group of procedures there is in the country,” Bilfinger said. For a procedure like back surgery, it might be difficult to come up with a comparable study, although Bilfinger said he “suspects strongly that this is a very similar relationship.”

Shroyer and Bilfinger will extend their work to another cardiothoracic operation. They have submitted a proposal to the Society of Thoracic Surgeons to start a parallel project to look at the difference in risk-adjusted outcomes for mitral valve procedures that compare single-center versus multicenter surgeons. The diversity of procedures may need to be considered in comparing single and multicenter surgeons.

Bilfinger said he recognizes that some doctors and hospital networks may find these conclusions disconcerting. It may give them pause in the internal discussion about value added by new satellites in any system, he explained. “This is worth a public debate. This is one of these aspects of modern health care that the consumer is not aware of.” The average consumer may not put too much emphasis on this, although the sophisticated consumer on Long Island may change or make decisions based on this type of information, he said.

Shroyer and Bilfinger, who have worked on the same floor at the Health Sciences Center since Shroyer arrived from Colorado in 2007, decided to collaborate on this project after a discussion during lunch. The duo were eating at SBU’s Simons Center Café when they were discussing the differences in outcomes for single and multicenter surgical procedures. They submitted a request to access the National Adult Cardiac Surgery Database in 2014 to the Society of Thoracic Surgeons.

For patients who are going to have a cardiac surgical procedure, Shroyer recommends that people choose their surgeon and surgery center “wisely.” She recommends researching the surgeons and their corresponding center’s bypass specific outcomes. She highlights two publicly available resources, which are Adult Cardiac Surgery Database Public Reporting|STS Public Reporting Online and Doctor Ratings — Consumer Reports.

Shroyer cautions that these ratings are somewhat outdated, so she suggests patients ask their surgeons directly about their more recent outcomes. She would also recommend contacting patients.

After conducting this study, Shroyer believes it would likely help patients if they searched for doctors who only perform bypass procedures at a single hospital. She also believes it is important for patients to consider surgeon-specific and center-specific risk-adjusted outcomes.

Ultimately, she said, the decision about a surgeon and a site for surgery is an important one that patients should make based on the likelihood of the best outcome.

“Patients should research their cardiac surgeon-hospital decision even more carefully than if they were buying a new home or a new car,” she explained in an email. “Their future health lies in their cardiac surgeon’s hands.”

Maurizio Del Poeta. File photo from SBU

By Daniel Dunaief

Sometimes, fixing one problem creates another.

People with multiple sclerosis have been taking a medication called fingolimod for a few years. The medicine calms immune systems that attack the myelin around nerve cells. Fingolimid decreases the lymphocyte number in the bloodstream by trapping them in the lymph nodes.

In a few cases, however, the drug can reduce the immune system enough that it allows opportunistic infections to develop. Cryptococcosis, which is a fungal infection often spread through the inhalation of bird droppings or from specific trees such as eucalyptus, is one of these infections, and it can be fatal if it’s not caught or treated properly, especially for people who have weakened immune systems.

Swiss pharmaceutical giant Novartis contacted Stony Brook University fungal expert Maurizio Del Poeta, a professor in the Department of Molecular Genetics & Microbiology, to understand how this drug opens the door to this opportunistic and problematic infection. He is also exploring other forms of this drug to determine if tweaking it can allow the benefits without opening the door to problematic infections.

Most of the human population has been exposed to this fungus. In a study in the Bronx, over 75 percent of children older than 2 years of age had developed an antibody against Cryptococcus neoformans, which means they have been exposed to it. It is unknown whether these people harbor the fungus or if they have just mounted an immune reaction. Exposure may be continuous, but infections may only occur if a person is immunocompromised.

Fingolimid “inhibits a type of immunity” that involves the movement of lymphocytes from organs into the bloodstream,” Del Poeta said. “Because of this, there are certain infections that can develop.”

Through a spokeswoman, Novartis explained that the company was “happy to have started a scientific collaboration” with Del Poeta to understand the role of a specific pathway in cryptococcus infections.

Cryptococcal meningitis is one of several infections that can develop. Others include herpes meningitis and disseminated varicella zoster. Before starting fingolimid, patients need to receive immunization for varicella zoster virus. At this point, doctors do not have a vaccine for cryptococcosis.

To study the way this drug and its derivatives work, Del Poeta recently received a $2.5 million grant over a five-year period from the National Institutes of Health.

Yusuf Hannun, the director of the Cancer Center at SBU, was confident Del Poeta would continue to be successful in his ongoing research.

Del Poeta “does very important and innovative work on fungal pathogenesis and he is a leader in the field,” Hannun wrote in an email. “His work will enhance our understanding of the molecular mechanisms.”

Fingolimid mimics a natural lipid. Years ago, Del Poeta showed that this sphingolipid, which is on the external surface of the membrane, is important to contain cryptococcosis in the lung. If its level decreases, the fungus can move from the lung to the brain.

While people with multiple sclerosis have developed signs of this infection, it is also prevalent in areas like sub-Saharan Africa, where people with AIDS battle cryptococcosis. About 40 percent of this HIV population develops this fungal infection, Del Poeta said. About 500,000 people die of cryptococcosis every year.

In certain areas of the United States, such as the Pacific Northwest, this fungus is also endemic. On Vancouver Island, about 19 people died from Cryptococcus gattii infections between 1999 and 2007. Most of those patients were immunocompromised.

When the fungus migrates from the lung to the brain, it is “very difficult, if not impossible in most cases, to eradicate,” Del Poeta explained in an email. If the diagnosis is made early enough before the infection spreads to the brain, the recovery rate is high, he suggested. In people whose immune systems are not compromised by drugs or disease, “death is rare.” 

Del Poeta plans to study the interaction between the drug and the fungal infection through a mouse model of the disease. The mouse model mimics the human disease and will provide insights on how to control the infection, particularly when the fungus reaches the brain.

Some of the derivatives Novartis has developed do not cause a fungal infection. Del Poeta is working with Novartis to study other forms of fingolimid that do not reactivate cryptococcosis. Del Poeta said Novartis is currently in Phase III clinical trials for another drug for multiple sclerosis. The new drug acts on a different receptor.

“We think the reason the fingolimid reactivates cryptococcosis is that it is blocking one receptor, which is important for the containment” of the fungus. The other drug doesn’t allow the disease-bearing agent to escape.

“This is a hypothesis,” Del Poeta said. He is waiting to corroborate the cell culture data in animal models.

Del Poeta has been working with Novartis for over three years. The Stony Brook scientist used some preliminary studies on the way fingolimid analogs behave as part of the research grant application to the NIH that led to the current grant.

Del Poeta said he is excited about the possibility of contributing to this area.

“Not only will this work contribute to the field of MS, but it will also have a contribution to the field of cryptococcosis,” he said. “This will have important implications for MS patients [and] for the entire HIV population.” He said he believes patients may have some other defect. If he is able to discover what that is, he may be able to protect them from a cryptococcosis infection.

Ultimately, Del Poeta hopes this work leads to a broader understanding of fungal infections that could apply to other pathogens as well.

Mycobacterium tuberculosis causes a granuloma very similar to the one caused by the cryptococcosis and we could potentially study whether the same molecular mechanisms involved in the control of the infection in the lung are similar between the two infections,” he explained in an email.

First Row from Left to Right: Kapeel Chougule, Computational Science Developer II; Mariana Neves Dos Santos Leite, Lab Aide (no longer at CSHL); Sharon Wei, Computational Science Analyst II; Andrew Olson, Computational Science Analyst II Second Row from Left to Right: Joshua Stein, Computational Science Manager III; Christos Noutsos, Postdoctoral Fellow (no longer at CSHL); Vivek Kumar, Computer Scientist; Doreen Ware, CSHL Adjunct Associate Professor & USDA/ARS Research Scientist; Yinping Jiao, Post Doc Computational; Sunita Kumari, Computational Science Analyst III; Marcela Tello-Ruiz, Computational Science Manager II; Young Koung Lee, Post Doc 11; Jerry Lu, Computational Science Developer III; Michael Regulski, Research Investigator Third Row from Left to Right: Christophe Liseron-Monfils, Post Doc Computational (no longer at CSHL); Bo Wang, Post Doc Computational; Liya Wang, Computational Science Manager III; Joseph Mulvaney, Computational Science Analyst III (no longer at CSHL); Lifang Zhang, Research Associate; James Thomason, Computational Science Developer III; Peter Van Buren, Systems Engineer III Not Pictured but in Ware Lab: Nicholas Gladman, Post Doc III; Fangle Hu, Research Technician II; Demitri Muna, Computational Science Analyst III; Pragati Muthukumar, Lab Intern, High School; Xiaofei Wang, Computational Science Analyst I; George Wang, Lab Intern, College; Christy Bedell, Senior Scientific Administrator. Photo by William Ware

By Daniel Dunaief

In a two-month span, members of Doreen Ware’s lab at Cold Spring Harbor Laboratory have published three articles that address fundamental properties of plants. 

Doreen Ware. Photo by Gina Motisi, Cold Spring Harbor Laboratory

Printed in the journal Nature Genetics, researchers in her lab studied the genes involved in conferring disease resistance across a range of species of rice. Another study, featured in Nature Communications, found the genes and the molecular pathway that determines the number of fertile flowers in the cereal crop sorghum.

In Frontiers in Plant Science, her productive team identified the causal genes that enable sorghum to develop a waxy outer layer that allows it to resist drought by containing water vapor.

 

“I am pleased with the recent publications from the laboratory,” Ware, who is also a computational biologist for the U. S. Department of Agriculture, explained in an email. “This is a sign of productivity, as well as the impact [technological] advances and drop in sequencing [costs] that is supporting these science advancements.”

Her lab is interested in the link between the genes in a plant and the way it develops.

“I want to understand mechanistically how the outputs in a genome interact with one another to produce a product,” Ware said. This will allow the lab to inform breeding models. “We would like to use the biological mechanism to support predictive modeling.”

In the rice article, Ware, informatics manager Joshua Stein at Cold Spring Harbor Laboratory and University of Arizona plant scientist Rod Wing searched for the specific genetic sequences different species of rice around the world use to develop resistance to infections by fungi, bacteria and other pathogens.

They used wild varieties of rice that had not been domesticated and looked for signals in the DNA. These were selected by their collaborators based on phenotypes that may be of value to introduce into domesticated varieties.

Stein looked at rice in areas including Asia, Africa, South America and Australia. Through this analysis, he was able to focus on specific genetic sequences that helped these species survive local threats.

As a first step, Stein explained, they have identified all of the genes in these species, but do not yet know which are important for local adaption. This article could provide information on the region of the genome that had disease genes that have been successful over time against threats in the environment.

One potential route to reducing dependency on pesticides is to introduce natural resistance or tolerance. By providing multiple ways of defending itself, a plant can reduce the chance that a pathogen can overcome all of these defenses.

“This is a similar strategy that is used to address both viral diseases and cancer treatment,” Ware explained.

Boosting the defenses of some of these crops with genes that have worked in the past is one strategy toward sustainability, although the scientists would need to work on the specifics to see how they were deployed.

Stein explained that his role in this specific study was to annotate the genes by using computer programs to look at DNA sequences. Stein used a process called comparative genomics, in which he studied the genes of numerous species of rice and compared them to look for similarities and differences.

“Because these different species grow in different climates and geographical ranges, they will be locally adapted to those regions,” Stein said. “Those genes might be important to improve cultivated rice.”

As climates change and people and materials such as seed crops move around the world, rice may need to develop a resistance to a bacteria or fungi it hasn’t encountered much through its history. Indeed, even those species of rice that haven’t moved to new areas may face threats from new challenges, such as insects, fungi, bacteria and viruses, that have moved into the area.

By understanding successful adaptive strategies, researchers like Ware and Stein can look for ways to transfer these defenses to other rice varieties.

Stein likens the process to an arms race that pits pathogens against food crops. “There are real examples of where a resistance gene has been transferred from a wild species to a cultivated species using traditional approaches,” he said. This includes knocking out specific genes in wheat that provide powdery mildew resistance.

Ware’s lab also produced an article in which they explored the genetic pathway that tripled the grain number of sorghum. The grain is produced on the panicle, which has many branches. In a normal plant, more than half of the flowers are not fertile, producing fewer grains.

“We have recently published a paper on a variety of sorghum where nearly all of the flowers are fertile, increasing the grain number on each head,” said Ware.

The work was led by Yinping Jiao and Young Koung Lee, postdoctoral researchers in Ware’s lab. Jiao focused on the computational analysis while Lee explored the development.

The researchers reduced the level of a hormone, which generated more flowers and more seeds. Other researchers could take a similar approach to boost yield in other grain crops.

Employing a commonly used technique to introduce new variation to support trait development, Department of Agriculture plant biologist Zhanguo Xin created a new variant that resulted in a change in a protein. This plant had a lower level of the hormone jasmonic acid in the developing flower. The researchers believe a reduction in the activity of a transcription factor that controls gene regulation caused this.

“We are currently exploring if this is associated with a direct or indirect interaction with biosynthetic genes required to make the plant hormone,” Ware said.

Early in January, Ware’s lab also produced a study in which they used mutations in sorghum to reveal the genetic mechanism that enables the plant to produce a wax that helps with its drought resistance.

Ware suggested these studies are linked to an underlying goal. “In human health, genomics and mechanism support the development of management of disease and in some cases cures,” she explained. “In agriculture, it leads to improved germplasm development and sustained agriculture.”

Sherif Abdelaziz. Photo by Juliana Thomas, SBU

By Daniel Dunaief

When the temperature drops dramatically, people put on extra layers of clothing or rush inside. At the other extreme, when the mercury climbs toward the top of thermometers, they turn on sprinklers, head to the beach or find cold drinks.

That, however, is not the case for the clay that is often underneath buildings, cliffs or the sides of hills on which people build picturesque homes. Clay shrinks after heating-cooking cycles in summer and also after freezing-thawing cycles in winter. “We want to understand why and how this behavior happens,” said Sherif Abdelaziz, an assistant professor in the Department of Civil Engineering at Stony Brook University.

Sherif Abdelaziz. Photo by Juliana Thomas, SBU

Abdalaziz recently received a prestigious Young Investigator Program award from the U.S. Army Research Office, which will provide $356,000 in funding over three years to study these properties. While the work will explore the basic science behind these clay materials, his findings could have a broad range of applications, from providing potential early-warning systems for future landslides or mudslides to monitoring coastal bluffs to keeping track of the soil around high-temperature nuclear waste buried in the ground.

Miriam Rafailovich, a distinguished professor in the Department of Materials Science at SBU who is beginning a collaboration with Abdelaziz, suggested that Abdelaziz’s work is relevant in multiple areas. “It applies to shoring infrastructure,” she wrote in an email. “The collapse of roadbeds under heavy traffic is a very common problem.”

Additionally, the clay around nuclear waste is subjected to very high temperatures during the period the waste is active. These temperatures recover to initial temperature with time, which will mainly subject the clay to a heating-cooling cycle that is part of this study, Abdelaziz explained. He is pleased to have the opportunity to explore these kinds of questions.

The Young Investigator Program award is “one of the most prestigious honors bestowed by the Army on outstanding scientists beginning their independent careers,” explained Julia Barzyk, a program manager in earth materials and processes at the U.S. Army Research Office, in an email. Abdelaziz’s research “is expected to contribute to improved approaches to mobility and siting and maintenance of infrastructure, especially in cold regions such as the Arctic.”

The field in which Abdelaziz works is called the thermomechanical behavior of soil. The challenge in this area, he said, is that the scientists are often divided into two groups. Some researchers focus on the heating effect on soil, while others explore cooling. In the real world, however, soil is exposed to both types of conditions, which could affect its ability to support structures above or around it.

In general, Abdelaziz has focused on clay. So far, scientists have looked at a piece or chunk of clay to see how it behaves. They haven’t done enough exploration at the microscale level, he said. “Our scientific approach crosses between the scales,” he said. In conducting experiments at SBU and at Brookhaven National Laboratory, he starts at the microscale and looks at the larger macroscale.

At the National Synchrotron Light Source II at BNL, Abdelaziz and his partners at BNL, including Eric Dooryhee, the beamline director for the X-ray Powder Diffraction beamline, change the temperature of the clay and look at the microstructure.

The challenge in the experiments they conducted last year was that they could change the temperature, but they couldn’t mimic the pressure conditions in the ground. Recently, they conducted the first experiments on a sample environment that involved a change in temperature and pressure and they got “good results so far,” Abdelaziz said in an email. He is looking for more beam time in the summer to finish the development of the sample environment. He is also seeking funding for a project to develop an early-warning system for coastal bluff stability.

“We are pretty good at predicting the weather,” Abdelaziz said. “What we don’t know is how this storm will impact our slopes.” The goal of the work he’s exploring now is to use what he learns from these experiments to predict potential changes in the soil. The purpose of this work is to better engineer mitigation techniques to avoid evacuations.

Abdelaziz’s work has focused on one clay type. He has, however, built a numerical model using experimental data. Once that model is validated, it will be able to predict the behavior of other clay, and he can include the heterogeneity of earth surface material in his numerical studies.

Rafailovich appreciates Abdelaziz’s dedication to his research. “He is very passionate about his work,” she wrote in an email. “He really hopes that he can change the world, one small road at a time.”

A native of Cairo, Egypt, Abdelaziz lives in Smithtown with his wife Heba Elnoby and their children Mohamed, 10, and Malak, 7. The father of two suggested that he “owes every single piece of success” in his career to the support he received from his wife.

The idea to study coastal bluff stability came to Abdelaziz when he was grilling on the beach a few years ago. He saw a sign that indicated that a bluff was unstable and that there was excessive movement. He related that to what he was studying. Abdelaziz is pleased with the funding and with the opportunity to contribute basic knowledge about clay to civil and military efforts. The financial support from the Army suggests that his “work is meaningful to the nation in general,” he said.

The flowering plant Amborella trichopoda is the oldest ancestral form of the angiosperms .

By Elof Axel Carlson

Elof Axel Carlson

Flowering plants are familiar to us as bouquets and garden plantings that delight us as they emerge in spring and summer. They are collectively part of the angiosperms, which also include familiar trees with generous-sized leaves that are shed in the fall.

They first appear in the fossil record about 130 million years ago. For those not familiar with how old life on Earth is estimated to be by biologists, that is about 60 million years before the dinosaurs went extinct.

Ferns, mosses and conifer trees (like gingkoes) existed long before the angiosperms. If the angiosperms are arranged in a sequence from oldest to most recent types, the oldest ancestral form of the angiosperms alive today is found in the Pacific Ocean on New Caledonia, an island northeast of Australia and northwest of New Zealand. That flowering plant is known as Amborella trichopoda.

A lot has been learned about the biology and history of Amborella. Its pollen, or ovule, has 13 chromosomes (and thus its leaf, stem and root cells have 26 chromosomes each). The Amborella ancestor gave rise to 250,000 species of flowering plants. About 75 percent of them have seeds with two fleshy modified leaves called cotyledons.

If you eat a fresh green pea from a pod and look at it before you pop it into your mouth, it has two halves, which is why you call it split pea soup when you cook a bag of dried peas.

The flower of the Amborella trichopoda

The DNA of Amborella has been worked out. It has 870 million base pairs. These are organized as 25,347 genes. Shortly before Amborella arose, it had experienced a doubling of its chromosome number. No major changes have occurred in its chromosomes since that event. Its nuclear genes have few inserted repetitive sequences. But, curiously, its mitochondrial DNA has many horizontally transferred genes from algae, mosses and lichens.

The ancestral genome of the angiosperms can be inferred because the major branches of the angiosperms share that core set of genes. This will allow botanists and chemists studying plant evolution to work out the functions of these shared genes as well as the distinctive genes that gave rise to the six major branches of flowering plants.

Quite different is the loblolly pine. It is a gymnosperm rather than angiosperm. They have a much longer history on Earth than the angiosperms. The conifers are the most familiar of the gymnosperms whose seeds are “naked” and enclosed in cones. Imagine the pine cones used in foods and compare them to the peas and beans in your soups.

The loblolly pine can live up to 300 years.

The loblolly pine, or Pinus taeda, is a common pine tree found from Florida to Texas and as far north as New Jersey. The trees can live 300 years and they are a major source of industrial lumber and paper pulp. The name loblolly is from an English idiom for food boiled in pots producing soups, broths or porridges. It has the largest known genome of any living organism, 23.2 billion base pairs (about seven times more than human cells and about 22 times that of Amborella. Unlike Amborella, 82 percent of its DNA is repetitive (formerly called junk DNA) caused by infectious insertions of tiny sequences of DNA. It has 50,172 genes in its pollen, or ovule, genome and they are located in 12 chromosomes per gamete.

One of my six students who got their doctorates with me at UCLA, Ronald Sederoff, pioneered the molecular biology of woody plants using the loblolly pine. He devised a technique to insert genes into woody plants, enabling his laboratory to study how wood is formed and how genes could be studied without waiting many years to study their genetics.

I was very pleased to learn that he was the recipient of the Wallenberg Prize, which is given by the king of Sweden for a contribution to plant biology, a field that is usually overlooked in the Nobel physiology and medicine prize. He attended the ceremony in Stockholm last October.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

From left, Jason Sheltzer, Nicole Sayles (who is a former lab technician and a co-author of an earlier MELK paper) and SBU undergraduates Chris Giuliano and Ann Lin. Photo by Constance Brukin

By Daniel Dunaief

If eating macaroni and cheese made Joe sick, he might conclude he was allergic to dairy. But he could just as easily have been allergic to the gluten in the macaroni, rendering the dairy-free diet unnecessary.

Scientists try to connect two events, linking the presence of a protein, the appearance of a mutation or the change in the metabolic activity of a cell with a disease. That research often leads to targeted efforts to block or prevent that protein. Sometimes, however, that protein may not play as prominent a role as originally suspected. That is what happened with a gene called MELK, which is present in many types of cancer cells. Researchers concluded that the high level of MELK contributed to cancer.

Jason Sheltzer, a fellow at Cold Spring Harbor Laboratory, and Ann Lin and Christopher Giuliano, undergraduates at Stony Brook University who work in Sheltzer’s lab, proved that wasn’t the case. By rendering MELK nonfunctional, Sheltzer and his team expected to block cancer. When they knocked out MELK, however, they didn’t change anything about the cancer, despite the damage to the gene. But, Sheltzer wondered, might there be some link between MELK and cancer that he was missing? After all, scientists had found a drug called OTS167 that was believed to block MELK function.

To test this drug’s importance for MELK and cancer, Sheltzer used this drug on cancer cells that didn’t have a functioning MELK gene or protein. Even without MELK, the drug “killed cancer cells,” regardless of the disappearance of a gene that researchers believed was important for cancer’s survival, he said.

“We showed for the first time that [the drug] was killing cells that didn’t express MELK,” Sheltzer said. The drug had to have another, unknown target.

Sheltzer suggested that this is the first time someone had used CRISPR, a gene-editing technique, to take a “deep dive” into what a drug is targeting. This drug, he said, has a different mechanism of action from the one most people believed.

Sheltzer, whose work was published in early February in eLife, expanded the research from a petri dish, where researchers grow and study cells, to mouse models, which are often more similar to the kinds of conditions in human cancers. In those experiments, he found no difference between the tumors that grew with a MELK gene and those that didn’t have the MELK protein, continuing to confirm the original conclusion. “The tumors that formed in cells that had MELK and the tumors that formed in cells that didn’t have MELK were the same size,” he said.

Originally, Sheltzer believed the MELK protein might be involved in chemotherapy resistance. His lab found, however, that no matter what they did to MELK in these cells, the cancer appeared indifferent. Other researchers suggested that Sheltzer’s work would be instructive in a broader way for scientists.

Sheltzer’s research on MELK “will motivate a new set of standards for target discovery and validation in the field going forward,” Christopher Vakoc, an associate professor at CSHL, explained in an email. Sheltzer “brings a rigorous approach to cancer research and an impressive courage to challenge prevailing paradigms.” Sheltzer’s work highlights the challenge of understanding the mechanism of action of new medicines, Vakoc added.

Sheltzer plans to explore several other genes in which a high concentration of a specific protein coded by that gene correlates with a poor prognosis.

Using CRISPR, Sheltzer believes his lab can get precise information about drug targets and their effect on cancer. He’s also tracing a number of other types of cancer drugs that he thinks might have compelling properties and will use CRISPR to study the action of these drugs. “We want to know not just that a drug kills cancer cells: We want to know how and why,” he said.

By figuring out what a drug targets, he might be able to identify the patients who are most likely to respond to a particular drug. So far, the finding that a drug doesn’t work by interfering with a specific gene, in this case MELK, has been easier than finding the gene that is the effective target, he explained.

One of Sheltzer’s goals is to search for a cancer cell that is resistant to the drug, so that he can compare the genes of the vulnerable one with those of the cell that’s harder to treat. Detecting the difference in the resistant cell can enable him to localize the region critical for a drug’s success.

Sheltzer said finding that MELK was not involved in a cancer’s effectiveness was initially “depressing” because researchers believed they had found a cancer target. “We hope that by publishing these techniques and walking through the experiments in the paper that other labs can learn from this and can use some of the approaches we used to improve their drug discovery pipelines,” he said.

Sheltzer is pleased that Lin and Giuliano made such important contributions to this paper. CRISPR has made it possible for these undergraduates to “make these really important discoveries,” he said. Lin, who has worked in Sheltzer’s lab for two and a half years, was pleased. “It is very exciting to share my knowledge of MELK in regards to its role in cancer biology,” she wrote in an email. “Authoring a paper requires a great deal of work and I am super thrilled” to see it published.

Sheltzer, who lives with his partner Joan Smith, who is a software engineer at Google, said he was interested in science during his formative years growing up in Wayne, Pennsylvania, which is just outside of Philadelphia, and appreciates the position he has at Cold Spring Harbor Laboratory. Soon after earning his doctorate at MIT, Sheltzer set up his own lab, rather than conducting research for several years as a postdoctoral researcher. “I was really fortunate to be given that opportunity,” he said.

As for his work with MELK, Sheltzer hopes he’s saved other labs from pursuing clinical dead ends.

Adélie penguins jump off an iceberg of one of the Danger Islands. Photo by Rachel Herman from Stony Brook University/ Louisiana State University

By Daniel Dunaief

In October of 1957 when the Soviet Union launched the satellite Sputnik, people imagined that satellites hovering over their heads could see everything and anything down below. Indeed, in the early days, some Americans rushed to close their blinds, hoping the Kremlin couldn’t see what they might be eating for dinner or watching on TV.

Satellites today collect such a wealth of information about the world below that it’s often not easy to analyze and interpret it.

That’s the case with the Danger Islands in the Antarctic. Difficult for people to approach by boat because of treacherous rocks around the islands and sea ice that might trap a ship, these islands are home to a super colony of Adélie penguins that number 1.5 million.

Nesting Adelie penguins. Photo by Michael Polito from Louisiana State University

This discovery of birds that were photographed in a reconnaissance plane in 1957 but haven’t been studied or counted since “highlights the ultimate challenge of drinking from the firehose of satellite-based information,” said Heather Lynch, an associate professor of ecology and evolution at Stony Brook University and a co-author on a Scientific Reports publication announcing the discovery of these supernumerary waterfowl.

Adélie penguins are often linked to the narrative about climate change. Lynch said finding this large colony confirms what researchers knew about Adélie biology. In West Antarctic, it is warming and the population is declining. On the eastern side, it’s colder and icier, which are conditions more suited for Adélie survival. The Danger Islands are just over the edge of those distinct regions, on the eastern side, where it is still cold and icy.

A population discovery of this size has implications for management policies. At this point, different groups are designing management strategies for both sides of the peninsula. A German delegation is leading the work for a marine protected area on the east side. An Argentinian team is leading the western delegation.

Adelie penguins on sea ice next to Comb Island. Photo by Michael Polito, Louisiana State University

This discovery supports the MPA proposal, explained Mercedes Santos, a researcher from the Instituto Antártico Argentino and a co-convener of the Domain 1 MPA Expert Group. The MPA proposal was introduced in 2017 and is under discussion in the Commission for the Conservation of Antarctic Marine Living Resources, where the United States is one of 25 members.

Said Santos in a recent email, “This publication will help us to show the importance of the area for protection, considering that decisions should be made [with the] best available information.” The location of the Danger Islands protects it from the strongest effects of climate change, as the archipelago is in a buffer zone between areas that are experiencing warming and those where the climate remains consistent over longer periods of time.

Whales and other mammals that eat krill create an unknown factor in developing fisheries plans. While penguins spend considerable time above water and are easier to monitor and count, the population of whales remains more of a mystery.

Heather Lynch with a penguin. Photo from Heather Lynch

Lynch said the more she studies penguins, the more skeptical she is that they can “stand in” as ecosystem indicators. Their populations tend to be variable. While it would be simpler to count penguins as a way to measure ecosystem dynamics, researchers also need to track populations of other key species, such as whales, she suggested. Humpback whales are “in competition with penguins for prey resources,” Lynch said.

The penguin data is “one piece of information for one species,” but MPAs are concerned with the food web for the entire region, which also includes crabeater seals. For the penguin population study, Lynch recruited members of her lab to contribute to the process of counting the penguins manually. “I figured I should do my fair share,” she said, of work she describes as “painstaking.” Indeed, Lynch and her students counted over 280,000 penguins by hand. She and her team used the hand counting effort to confirm the numbers generated by the computer algorithm.

“The counting was done to make sure the computer was doing its job well,” she said. She also wanted to characterize the errors of this process as all census counts come with errors and suggested that the future of this type of work is with computer vision.

Lynch appreciated the work of numerous collaborators to count this super colony. Even before scientists trekked out to the field to count these black and white birds, she and Matthew Schwaller from NASA studied guano stains on the Danger Islands in 2015 using existing NASA images.

The scientific team at Heroina Island in Antarctica. Photo by Alex Borowicz, Stony Brook University

This penguin team included Tom Hart from Oxford University and Michael Polito from Louisiana State University, who have collaborated in the field for years, so it was “natural that we would work together to try and execute an expedition.” Stephanie Jenouvrier, a seabird ecologist at the Woods Hole Oceanographic Institute, has considerable expertise in the modeling side, especially with the climate; and Hanumant Singh, a professor of mechanical and industrial engineering at Northeastern University has experience using drones in remote areas, Lynch said.

The penguins on the Danger Islands react to the presence of humans in a similar way to the ones elsewhere throughout the Antarctic. The birds generally don’t like creatures that are taller than they are, in part because they fear skuas, which are larger predatory birds that work together to steal an egg off a nest. Counting the penguins requires the researchers to stand, but when the scientists sit on the ground, the penguins “will approach you. You have to make sure you’re short enough.”

Lynch would like to understand the dynamics of penguin nest choices that play out over generations. She’s hoping to use a snapshot of the layout of the nests to determine how a population is changing. Ideally, she’d like to “look at a penguin colony to see whether it’s healthy and declining.” She believes she is getting close.

From left, Karen Chen-Wiegart, Silvia Centeno from the Metropolitan Museum of Art and BNL’s Juergen Thieme and Garth Williams in front of a computer image of Jan Van Eyck’s ‘Crucifixion,’ which they used to study the effects of soap formation in oil paintings. Photo from BNL

By Daniel Dunaief

Paintings can be so evocative that they bring images and scenes to life, filling a room with the iridescent flowers from an impressionist or inspiring awe with a detailed scene of human triumph or conflict. While the paints themselves remain inanimate objects, some of them can change over time, as reactions triggered by anything from light to humidity to heat can alter the colors or generate a form of soap on the canvas.

Recently, a team led by Silvia Centeno, a research scientist of the Department of Scientific Research at the Metropolitan Museum of Art in New York City, explored the process that caused lead-tin yellow type I to form an unwanted soap. Soap formation “may alter the appearance of paintings in different ways, by increasing the transparency of the paints, by forming protrusions that may eventually break through the painting surface, or by forming disfiguring surface crusts,” Centeno explained in an email.

Karen Chen-Wiegart with her husband Lutz Wiegart at Paumanok Vineyards in Aquebogue in November of 2017. Photo by Jen You

A team that included Karen Chen-Wiegart, who is an assistant professor at Stony Brook  University and has a joint appointment at Brookhaven National Laboratory, looked specifically at what caused a pigment common in numerous paintings to form these soaps. The research proved that the main component in lead-tin yellow pigment reacts, Centeno said. The causes may be environmental conditions and others that they are trying to discover. Lead-tin yellow changes its color from yellow to a transparent white. The pigment was widely used in oil paintings.

The pigment hasn’t shown the same deterioration in every painting that has the reactive ingredients, which are heavy-metal-containing pigments and oil. This suggests that specific environmental conditions may contribute to the pace at which these changes occur. Most of the time, the changes that occur in the paintings are below the surface, where it may take hundreds of years for these soaps to form.

The scientists are hoping this kind of research helps provide insights that allow researchers to protect works of art from deterioration. Ideally, they would like a prognostic marker that would allow them to use noninvasive techniques to see intermediate stages of soap formation. That would allow researchers to follow and document change through time. The scientists analyzed a microscopic sample from the frame of a painting from Jan Van Eyck called “Crucifixion,” which was painted in 1426.

Samples from works of art are small, around several microns, and are usually removed from areas where there is a loss, which prevents any further damage. Samples are kept in archives where researchers can do further analysis. In this case, a microscopic sample was taken from the frame of the painting, from an area where there was already a loss.

Centeno worked with a group led by Cecil Dybowski, a professor in the Department of Chemistry and Biochemistry at the University of Delaware, who has used solid-state nuclear magnetic resonance spectroscopy available at the university to study soap formation since 2011.

She also partnered with Chen-Wiegart to work at BNL’s National Synchrotron Light Source II, a powerful tool with numerous beamlines that can see specific changes on an incredibly fine scale. Centeno said she was very pleased to add Chen-Wiegart’s expertise, adding that she is “an excellent collaborator.”

When they started working together, Chen-Wiegart worked at BNL as an assistant physicist, and then became an associate physicist. As a beamline scientist, she worked at a beamline led by Juergen Thieme, who is a collaborator on this project as well. The researchers see this as an initial step to understand the mechanism that leads to the deterioration of the pigment.

The team recently applied for some additional beamline time at the NSLS-II, where they hope to explore how porosity, pore size distribution and pore connectivity affect the movements of species in the soap formation reactions. The humidity may have more impact in the soap formation. The researchers would like to quantify the pores and their effects on the degradation, Chen-Wiegart said.

In addition, Centeno plans to prepare model samples in which she accelerates the aging process, to understand, at a molecular level, what might cause deterioration. She is going to “try to grow the soaps in the labs, to see and study them with sophisticated techniques.”

Chen-Wiegart will also study the morphology at microscopic and macroscopic levels from tens of nanometers to microns. Both Centeno and Chen-Wiegart are inspired by the opportunity to work with older paintings. “I feel fortunate to have the opportunity to enjoy works of art as part of my daily work,” Centeno said.

Chen-Wiegart was eager to work with art that was created over 500 years ago. “The weight of history and excitement of this connection was something enlightening,” she said. “Thinking about it and processing it was a unique experience.”

A resident of Rocky Point, Chen-Wiegart lives with her husband Lutz Wiegart, who is a beamline scientist working at the Coherent Hard X-ray Scattering beamline at BNL. People assume the couple met at BNL, but their relationship began at a European synchrotron called ESRF in France, which is in Grenoble.

The couple volunteers at the North Shore Christian Church in Riverhead in its Kids Klub. For five days over the last five summers, they did science experiments with children who are from 4 to 11 years old.

The scientific couple enjoys the natural beauty on Long Island, while traveling to the city for cultural events. They kayak in the summer and visit wineries.

As for her work, Chen-Wiegart is excited about continuing her collaboration with Centeno.“The intersection between science, art and culture is inspiring for me.”

Anil Yazici, center, with Eren Ozguven, right, and Ayberk Kocatepe, left, who worked in Ozguven’s lab as a doctoral student, at a conference in Florida last year.Photo from Anil Yazici

By Daniel Dunaief

Anil Yazici wants to help the elderly population with transportation, public safety and emergency services and housing.

An assistant professor in civil engineering at Stony Brook University, Yazici is organizing a series of meetings to address the needs of the elderly. He is recruiting a host of speakers from around the world and is inviting the public to listen and participate in roundtable discussions for a two-day event at the Hilton Garden Inn at Stony Brook as a part of a Research Coordination Network.

The workshop schedule with a list of speakers will be available around mid-March. Those interested in attending can visit the website https://you.stonybrook/edu/agingpopulationrcn/events/rcn-workshops/.

Yazici received a $499,999 four-year grant from the National Science Foundation last fall to develop a way to study the connection between smart and connected communities and areas with varying resources and population densities. The group will host workshops at the University of Michigan and at Florida State University.

Anil Yazici, right, with Harold Walker, left, a professor and chair in the Department of Civil Engineering and Laura Coronel, center, a member of the class of 2017.Photo by Erin Giuliano

The goal is to maintain mobility and access to services for the aging population. “Our focus is to involve aging populations within smart and connected communities … which generally employ technology to address mobility and access,” he explained in an email.

Yazici would like to get the government, communities and researchers to work together to address these issues. Groups involved in the effort will produce white papers, which can provide a proposal to help governments and community organizations plan various services.

Jacqueline Mondros, the dean of SBU’s School of Social Welfare and assistant vice president for Social Determinants of Health, described housing and transportation as “two of the most problematic issues of older adults, particularly in suburbia and rural areas.”

Mondros, who will be giving one of the talks in April, hopes the tech sector and engineering dedicate more attention to this area. She believes this effort will provide a greater understanding of the kind of connectedness that will help seniors and their caregivers. She also hopes the initiative helps people learn “about the intersection between connectivity and technology and social intervention.”

The funding for this effort is designed to create networks and develop ideas. Further work to develop projects, however, would require additional financial support.

Developing a broad plan in an area such as transportation will require flexible and location-specific solutions. Indeed, Long Island reflects such varying dynamics. Areas in or closer to the city have higher population density and a deeper transportation infrastructure, with subways, buses and trains offering transportation throughout the area. Further out east, however, the population density drops considerably, limiting such options.

“Once you don’t drive” when you’re in suburbia “it’s almost impossible to get around and go where you need to go,” Mondros said. People end up in “social isolation [which] clearly creates poor health outcomes and depression.”

Presenters will include people with expertise from Europe and Australia who can bring the solutions they have developed through smart and connected communities. Some locations have developed a system to help the aging population with routine transportation.

Anil Yazici after he went spearfishing for Mediterranean parrotfish in Turkey.Photo by Meliha Yazici

In one community, Yazici learned about a personal network in which people call each other to provide rides for regular travel, like weekly doctor or hospital visits. The network, which was organized through a church, involved calls to find rides through church members.

Eren Ozguven, who met Yazici in high school in Turkey and is a collaborator on the project, plans to do a presentation at Stony Brook on the challenges the aging population faces during hurricanes.

That includes a look at “how the technology usage is shaping this and how [to] provide better accessibility and safety during evacuations and sheltering,” Ozguven, who is an assistant professor in the Department of Civil and Environmental Engineering at FAMU-FSU College of Engineering in Tallahasse, Florida, explained in an email. “We are hoping to have very fruitful brainstorming sessions with practitioners, researchers, students and the public.”

More broadly, Yazici’s work is focused on the resilience of various civil engineering systems, such as transportation.

Organizational networks require contact among all the various infrastructure agencies, he said. They need to keep in contact and make decisions through context. He is working on a way to measure resiliency, so that when storms break communication links and disrupt power grids, the agencies in charge of those systems can restore them to previous levels.

He would like to see how to make an agency’s response to a disruption more efficient. Resilience can be improved through developing sound models for a physical infrastructure response.

A resident of Harlem where he lived during his postdoctoral training, Yazici has had to create his own system to ensure a successful commute. He leaves early, before much of the reverse commuting traffic builds, and returns home late. Yazici, who has been at Stony Brook since the fall of 2014, said he appreciates the opportunity to contribute to a new and growing department.

Yazici moved eight times when he was younger, as the family followed his father Mesut, who was also a civil engineer, from projects including water treatment plants to industrial waste processing. His father tried to dissuade him from following in his footsteps. His academic position, however, doesn’t require Yazici to follow projects from one place to another.

Starting in his first year in college, Yazici played bass in a band. He performed mostly ’70s Turkish progressive rock. He enjoys making music and plans to start an ensemble with his students to have a live music event after graduation.

As for his work, Yazici appreciates the opportunity to study areas that cross disciplines and that help people. “What drives me and most of the academics I know is to make a difference in people’s lives,” he explained in an email. “This could be through teaching and seeing students evolve personally and professionally or researching a topic to solve a problem and improve someone’s life.”

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

By Daniel Dunaief

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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