Power of 3

From left, Libo Wu, Zhangjie Chen (both are doctoral students on the ARPA-E project), Ya Wang, Xing Zhang (graduated), Muzhaozi Yuan and Jingfan Chen (both are doctoral students on the NSF project). Photo courtesy of Stony Brook University

By Daniel Dunaief

Picture a chalkboard filled with information. It could include everything from the basics — our names and phone numbers, to memories of a hike along the Appalachian Trail, to what we thought the first time we saw our spouse.

Diseases like Alzheimer’s act like erasers, slowly moving around the chalkboard, sometimes leaving traces of the original memories, while other times removing them almost completely. What if the images, lines and words from the chalk could somehow be restored?

Ya Wang with former student Wei Deng at Stony Brook’s Advanced Energy Research and Technology Center. Photo courtesy of SBU

Ya Wang, a mechanical engineering assistant professor at Stony Brook University, is working on a process that can regenerate neurons, which could help with a range of degenerative diseases. She is hoping to develop therapies that might restore neurons by using incredibly small magnetic nanoparticles.

Wang recently received the National Science Foundation Career Award, which is a prestigious prize given to faculty in the early stages of their careers. The award lasts for five years and includes a $500,000 grant.

Wang would like to understand the way small particles can stimulate the brain to rebuild neurons. The award is based on “years of effort,” she said. “I’m happy but not surprised” with the investment in work she believes can help people with Alzheimer’s and Parkinson’s diseases.

“All neuron degeneration diseases will benefit from this study,” Wang said. “We have a large population in New York alone with patients with neuron degeneration diseases.” She hopes the grant will help trigger advancements in medicine and tissue engineering.

Wang’s “work on modeling the dynamic behavior of magnetic nanoparticles within the brain microenvironment would lay the foundation for quantifying the neuron regeneration process,” Jeff Ge, the chairman and professor of mechanical engineering, said in a statement.

Wang said she understands the way neurodegenerative diseases affect people. She has watched her father, who lives in China, manage through Parkinson’s disease for 15 years.

Ge suggested that this approach has real therapeutic potential. “This opens up the exciting new possibility for the development of a new microchip for brain research,” he said.

At this point, Wang has been able to demonstrate the feasibility of neuron regeneration with individual nerve cells. The next step after that would be to work on animal models and, eventually, in a human clinical trial.

That last step is a “long way” off, Wang suggested, as she and others will need to make significant advancements to take this potential therapeutic breakthrough from the cell stage to the clinic. 

She is working with a form of coated iron oxide that is small enough to pass through the incredibly fine protective area of the blood/brain barrier. Without a coating, the iron oxide can be toxic, but with that protective surface, it is “more biofriendly,” she said.

The size of the particles are about 20 nanometers. By contrast, a human hair is 80,000 nanometers thick. These particles use mechanical forces that act on neurons to promote the growth or elongation of axons.

Ya Wang. Photo from SBU

As a part of the NSF award, Wang will have the opportunity to apply some of the funds toward education. She has enjoyed being a mentor to high school students, some of whom have been Siemens Foundation semifinalists. Indeed, her former students have gone on to attend college at Stanford, Harvard and Cal Tech. “I was very happy advising them,” she said. “High school kids are extremely interested in the topic.”

A few months before she scored her NSF award, Wang also won an Advanced Research Projects Agency–Energy award for $1 million from the Department of Energy. In this area, Wang also plans to build on earlier work, developing a smart heating and cooling system that enables a system to direct climate control efforts directly at the occupant or occupants in the room.

Extending on that work, Wang, who will collaborate in this effort with Jon Longtin in the Department of Mechanical Engineering at SBU and Tom Butcher and Rebecca Trojanowski at Brookhaven National Laboratory, is addressing the problem in which the system no longer registers the presence of a person in the room.

Wang has “developed an innovation modification to a simple, inexpensive time-honored position sensor, but that suffers from requiring that something be moving in order to detect motion,” Longtin explained in an email. The sensors can’t detect a person that is not moving. The challenge, Longtin continued, is in fooling the sensor into thinking something is there in motion to keep it active.

Wang described a situation in which a hotel had connected an occupant-detecting system to its HVAC system. When a person fell asleep in the room, however, the air conditioning turned off automatically. On a hot summer night, the person was frustrated. She put colored paper and a fan in front of the sensor, which kept the cool air from turning off.

Instead of using a fan and colored paper, the new system Wang is developing cuts the flow of heat to the sensor, which enhances its ability to recognize stationary or moving people.

Wang and her colleagues will use low-power liquid crystal technology with no moving parts. “The sensor detects you because you are a human with heat,” she said. “Even though you are not moving, the amount of heat is changing.”

The sensor will be different in various locations. People in Houston will have different temperature conditions than those in Wisconsin. Using a machine-learning algorithm, Wang said she can pre-train the system to respond to different people and different conditions.

She has developed a smart phone app so that the house can react to the different temperature preferences of a husband and wife. People can also choose night or day modes.

Wang also plans to work on a system that is akin to the way cars have different temperature zones, allowing one side of the car to be hotter than the other. She intends to develop a similar design for each room.

From left, Jon Longtin, Sotirios Mamalis and Benjamin Lawler. Photo courtesy of Stony Brook University

By Daniel Dunaief

It’s not exactly Coke and Pepsi designing a better soda. It’s not Nike and Reebok creating a more efficient sneaker. And, it’s not McDonald’s and Burger King uniting the crown and the golden arches. At Stony Brook University, it is, however, a combination of energy systems that haven’t historically worked together.

“Fuel cells and engines have been seen as competing technologies,” said Sotirios Mamalis, an assistant professor of mechanical engineering at SBU. “The truth of the matter is that these two technologies are very complementary because of their operating principals.”

Indeed, Mamalis is the principal investigator on a multi-year project to create a hybrid fuel cell-engine system that recently won a $2.3 million award from the Department of Energy’s Advanced Research Projects Agency-Energy.

Working with Benjamin Lawler and Jon Longtin at Stony Brook and Tom Butcher, leader of the Energy Conversion Group at Brookhaven National Laboratory, Mamalis plans to build a system that uses solid oxide fuel cells partnered with a split-cylinder, internal combustion engine. The engine system will use the tail gas from the fuel cell to provide additional power, turning the inefficiency of the fuel cell into a source of additional energy.

“These ARPA-E awards are extremely competitive,” said Longtin, adding “If you land one of these, especially a decent-sized one like this, it can move the needle in a lot of ways in a department and at the university level.” The group expects that this design could create a system that generates 70 percent fuel to electricity efficiency. That is well above the 34 percent nationwide average.

Reaching that level of energy efficiency would be a milestone, said Longtin, a Professor in the Department of Mechanical Engineering at Stony Brook. The core of the idea, he suggested, is to take the exhaust from fuel cells, which has residual energy, and run that through a highly tuned, efficient internal combustion engine to extract more power. The second part of the innovation is to repurpose the cylinders in the engine to become air compressors. The fuel cell efficiency increases with higher pressure.

A fuel cell is a “highly efficient device at taking fuel and reacting it to produce DC electricity,” Lawler said. One of its down sides, aside from cost, is that it can’t respond to immediate needs. An engine is the opposite and is generally good at handling what Lawler described as transient needs, in which the demand for energy spikes.

The idea itself is ambitious, the scientists suggested. “These projects are high-risk, high-reward,” said Mamalis. The risks come from the cost and the technical side of things.

The goal is to create a system that has a disruptive role in the power generation market. To succeed, Mamalis said, they need to bring something to market quickly. Their work involves engineering, analysis and design prior to building a system. The project could involve more tasks to reduce technical risk but “we’re skipping a couple of steps so we can demonstrate a prototype system sooner than usual,” Mamalis said.

They will start by modeling and simulating conditions, using mathematical tools they have developed over the years. Once they have modeling results, they will use those to guide specific experimental testing. They will take data from the engine simulation and will subject the engine to conditions to test it in a lab. 

“The biggest challenges will be in changing the operation of each of these two technologies to be perhaps less than optimal for each by itself and then to achieve an integrated system that ends up far better,” Butcher explained in an email. “The target fuel-to-electricity efficiency will break barriers and be far greater than is achieved by conventional power plants today.”

Butcher, whose role will be to provide support on system integration concepts and testing, suggested that this could be a part of distribution power generation, where power is produced locally in addition to central power plants. People have looked into hybrid fuel cell-gas turbine systems in the past and a few have been installed and operational, Mamalis explained. The problem is with the cost and reliability.

Mamalis and his colleagues decided they can tap into the inefficiency of fuel cells, which leaves energy behind that a conventional engine can use. The reason this works is that the fuel cell is just inefficient enough, at about 55 percent, to provide the raw materials that a conventional engine could use. A fuel cell that was more efficient, at 75 or 80 percent, would produce less unused fuel in its exhaust, limiting the ability of the system to generate more energy.

The team needs to hit a number of milestones along the way, which are associated with fuel cell development and engine and hybrid system development.

The first phase of the work, for which the team received $2.3 million, will take two years. After the group completes Phase I, it will submit an application to ARPA-E for phase II, which would be for an additional $5 million.

Lawler suggested that fundamental research made this kind of applied project with such commercial potential possible. “The people who did fundamental work and [were involved in] the incremental steps led us to this point,” he said. “Incremental work leads to ground-breaking ideas. You can’t predict when groundbreaking work will happen.”

The other researchers involved in this project credit Mamalis for taking the lead on an effort that requires considerable reporting and updating with the funding agency.

Every three months, Mamalis has to submit a detailed report. He also participates in person and on conference calls to provide an update. He expects to spend about 90 percent of his time on a project for which the team has high hopes.

“It’s an exciting time to be a part of this,” Longtin said. “These folks are pivotal and we have developed into a very capable team, and we have been setting our sights on larger, more significant opportunities.”

Gholson Lyon. Photo courtesy of Cold Spring Harbor Laboratory

By Daniel Dunaief

With the cost of determining the order of base pairs in the human genome decreasing, scientists are increasingly looking for ways to understand how mutations lead to specific characteristics. Gholson Lyon, an assistant professor at Cold Spring Harbor Laboratory, recently made such a discovery in a gene called NAA15.

People with mutations in this gene had intellectual disability, developmental delay, autism spectrum disorder, abnormal facial features and, in some cases, congenital cardiac anomalies.

In a recent interview, Lyon explained that he is trying to understand how certain mutations influence the expression of specific traits of interest, such as intelligence, motor development and heart development. He’s reached out to researchers scattered around the world to find evidence of people who had similar symptoms, to see if they shared specific genetic mutations in NAA15 and found 37 people from 32 families with this condition.

“I really scoured the planet and asked a lot of people about this,” said Lyon, who recently published his research in The American Journal of Human Genetics. The benefit of this kind of work, he explained, is that it can help screen for specific conditions for families at birth, giving them an ability to get an earlier diagnosis and, potentially, earlier treatment. “Being able to identify children at birth and to know that they are at risk of developing these disorders would, in a perfect world” allow doctors to dedicate resources to help people with this condition, he said.

Lyon published a similar study on a condition he named Ogden syndrome seven years ago, in which five boys in a single family died before they reached the age of 3. A mutation in a similar gene, called NAA10, led to these symptoms, which is linked to the X chromosome and was only found in boys.

Lyon found the genes responsible on NAA15 by comparing people with these symptoms to the average genome. The large database, which comes from ExAC and gnomAD, made it possible to do a “statistical calculation,” he said. The next steps in the research is to look for protein changes in the pathway in which these genes are involved. The people he studied in this paper are all heterozygous, which means they have one gene that has a mutation and the other that does not.

With this condition, they have something called haploinsufficiency. In these circumstances, they need both copies of the fully functioning gene to produce the necessary proteins. These mutations likely decrease the function of the protein. Lyon would like to study each of these cases more carefully to understand how much the mutation contributes to the various conditions. He looked for evidence of homozygous mutations but didn’t find any. “We don’t know if they don’t exist” because the defective gene may cause spontaneous miscarriages or if they just didn’t find them yet, he said.

Lyon plans on reaching out to geneticist Fowzan Alkuraya, who was trained in the United States and is working at King Faisal Specialist Hospital and Research Centre clinic in Saudi Arabia. The geneticist has studied the genes responsible for a higher rate of genetic disorders linked to the more common practice of people having children with cousins in what are called consanguineous marriages. 

Alkuraya works on the Saudi Human Genome Program, which studies the inherited diseases that have a higher incidence in Saudi Arabia.

For Lyon, finding the people who carry this mutation was challenging, in part because it hasn’t run in the family for multiple generations. Instead, Lyon and his colleagues, including Holly Stessman of Creighton University in Omaha, Nebraska and Linyan Meng at Baylor College of Medicine in Houston, Texas, found 32 unrelated families. In some of these families, one or two siblings carried this mutation in a single mutation.

By defining a new genetic disease, the scientists could help families seeking a diagnosis, encourage the start of early intervention such as speech therapy and connect patients with the same diagnosis. This can provide a support network in which people with this condition and their families know they are not battling this genetic challenge alone, Meng, the assistant laboratory director at Baylor Genetics and assistant professor at Baylor College of Medicine, explained in an email.

Every patient with an NAA15 mutation won’t have the same symptoms. “We see a range of phenotypes in these patients, even though they carry the same diagnosis with defects in the same disease,” Meng added. “Early intervention could potentially make a difference for NAA15 patients.”

Lyon works as a psychiatrist in Queens providing medication management. During his undergraduate years at Dartmouth College, in Hanover, New Hampshire, Lyon said he was interested in neurology and psychology. As he went through his residency at NYU, Columbia and New York State Psychiatric Institute, he gravitated toward understanding the genetic basis of autism, which he said is easier than conditions like schizophrenia because autism is more apparent in the first few years of life.

Lyon recently started working part time at the Institute for Basic Research in Developmental Disabilities on Staten Island. While Lyon appreciates the opportunity to work there, he is concerned about a potential loss of funding. “These services are vital” on a clinical and research level, he said. He is concerned that Gov. Andrew Cuomo (D) is thinking about decreasing the budget for this work. Reducing financial support for this institution could cause New York to lose its premiere status in working with people with developmental disabilities, he said.

“It has this amazing history, with an enormous number of interesting discoveries in Down syndrome, Alzheimer’s disease and Fragile X,” he said. “I don’t think it gets enough credit.”

As for his work with NAA, Lyon plans to continue to search for other people whose symptoms are linked to these genes. “I am looking for additional patients with mutations in NAA10 or NAA15,” he said.

Romeil Sandhu with his dog June. Photo courtesy of Romeil Sandhu

By Daniel Dunaief

Romeil Sandhu has had a busy year.

Last fall, the U.S. Air Force awarded him a $450,000 three-year grant, called the Young Investigator Research Program. At the beginning of this year, Sandhu won a $500,000 National Science Foundation Career Award.

The assistant professor in the Department of Biomedical Informatics at Stony Brook University is working in several directions on basic research that could help with everything from network security to autonomous cars.

The awards are a “tremendous accomplishment,” Allen Tannenbaum, a distinguished professor of computer science and applied mathematics/statistics at SBU, explained in an email. Sandhu won the career award on his “first try, which is very unusual. The Air Force award is a very high honor for a young researcher.”

Tannenbaum was Sandhu’s doctoral thesis adviser at Georgia Tech. Tannenbaum recruited Sandhu to join Stony Brook University and described Sandhu’s work as going in a “very promising direction.”

The Air Force funding is a new direction in which Sandhu is developing a theory around how to incorporate user input in three-dimensional autonomous systems that rely on two-dimensional imaging information.

An example of this, Sandhu explained, is where a soldier might make judgments maneuvering a vehicle around potentially deadly situations. His work involves translating three-dimensional interactive feedback controls based on two-dimensional imaging systems.

“When you take a video of a car, it’s in two dimensions,” he explained. The computer link between the collected images and the reality relies on geometric properties.

With most autonomous computer systems, a human is involved in the process, to prepare for what is called the “unknown unknown.” That is a term used to describe situations in which there is no way to predict all possible events.

Through his Air Force work, Sandhu ideally would like to seek greater autonomy for some of these self-directed systems. Removing human input entirely, however, generates a risk that may be too great. That is the case in cancer treatment as well as the systems used to protect soldiers. The work he is doing with the Air Force explores how to fuse human and computer-assisted decision making.

The NSF award, meanwhile, will use the confluence of geometry and control to explore vulnerability in time-varying networks. Sandhu is tackling problems in social systems, communication systems and cancer biology and biomedical informatics.

“We can devise this idea of a network, which is the same way with cancer and proteins,” he said. One protein sends a signal to another, causing a cascade of reactions that often promote cancer.

Sandhu is interested in how microfluctuations can pave the way to larger disruptions. In the social setting, such information may infect individuals or groups and such dynamics may allow it to influence macroscopic audiences.

“The prevailing idea is that there exist several changes that pave the way to a larger catastrophic failure,” he explained in an email. 

The grant is designed to exploit everything that can be modeled as a part of a network, to understand their vulnerability. Viral information and trending stories, Sandhu said, might have one dynamic, while conspiracy theories might have another. He would like to see how such information gains traction and spreads.

The way people interact occurs through multiple networks. Sandhu is studying how models can exploit real-world behavior. Geometry, he suggests, can begin to assist on more complex modeling problems that are time varying and multilayered.

When he describes how he studies systems such as cancer, he likens the process to a waterbed. A drug or therapy may knock out a specific gene, which could limit cancer’s growth. When that gene changes, however, it creates a wave along the bed, enabling another potential genetic process to occur. While it has a more precise definition in control, it is akin to sitting on a waterbed in suppressing one sequence only to give rise to another.

Sandhu, who arrived at Stony Brook University in 2016, grew up in Huntsville, Alabama, and then spent over a decade going to school in Georgia, where he earned his doctorate at Georgia Tech.

In some ways, Sandhu’s Huntsville background, which includes lettering in high school soccer for four years as a center midfielder, is similar to one of the challenges in perception he studies through his work. 

“Think of me as one person in a network,” he said. “In a lot of the research we look at, we want to know how microfluctuations such as myself give way to a larger perception.”

Sandhu explained that the general perception of Huntsville and Alabama is different from his experience.

Most people are surprised that Huntsville has the second largest research park in the nation, at Cummings Research Park. Huntsville also has numerous aerospace companies.

The city generally ranks highly as one of the more educated in the country, he said. This is due in large part to the tech community that supports the government. The town is largely influenced by NASA and the surrounding military aerospace community, which Sandhu believes impacted his worldview, career path and research initiatives.

Indeed, one of the goals Sandhu has for his NSF grant is to help educate the high school students of people serving in the military. He said he appreciated the military families who were such an integral part of his upbringing.

Sandhu has two doctoral students and two master’s students in his lab. He also plans to participate in the Simons Summer Research Program at SBU where he will add a high school student. He is excited about the next phase of his research.

“The best part is the challenges that lie ahead,” he explained in an email. “Whether it is targeted therapy and cancer research, social computing and/or interactive computing, we are just beginning to understand very complex issues. Our hope is that we can make a contribution.”

Eli Stavitski. Photo by Alena Stavitski

By Daniel Dunaief

Humans learned to fly by studying birds and have learned to edit genes by understanding the molecular battle between bacteria and viruses. Now, we may also learn to take carbon dioxide, a necessary ingredient in photosynthesis, and use it to produce energy.

Eli Stavitski, a physicist at Brookhaven National Laboratory, is working with a new form of electrocatalyst to convert carbon dioxide into carbon monoxide, which can become part of an energy process.

Researchers have used noble metal electrocatalysts, such as gold and platinum, to promote this reaction. The problem with this method, however, is that these metals are rare and expensive.

In most of the reactions with other potential electrocatalysts, however, a competing reaction, called water splitting, reduces the amount of carbon monoxide produced.

Single atoms of nickel, however, woven into a lattice of graphene, which is a monolayer of carbon, produces a much higher amount of carbon monoxide, while minimizing the unwanted water splitting side reaction.

Indeed, these single atoms of nickel converted carbon dioxide to carbon monoxide with a maximum selectivity of 97 percent.

“The critical aspect of the work is that they show a change in chemical selectivity” resulting in the production of the desired products, Dario Stacchiola, a group leader in interface science and catalysis at the Center for Functional Nanomaterials at BNL, explained in an email. An important part of this study is the “ability to detect single atoms (atomic needles in a carbon-based graphene haystack) which is possible in [Stavitski’s] instrument.”

Stacchiola and Stavitski are collaborating on projects related to heterogeneous catalysis. They synthesize and test materials and then measure them in a state-of-the-art beamline. Carbon monoxide can be used to produce useful chemicals such as hydrogen, which can power fuel cell vehicles. The process can contribute to something called carbon sequestration, in which carbon dioxide is removed from the atmosphere.

While carbon monoxide is a deadly gas when it’s breathed in, Stavitski said manufacturing facilities deal with toxic substances regularly and have policies and procedures in place to minimize, monitor and contain any potential dangers. On the scale of toxicity, carbon monoxide isn’t the worst thing by far, he explained.

Indeed, in refining crude oil to fuels and chemicals, refining companies regularly produce highly toxic intermediates that they control during the manufacturing process.

The way researchers create the nickel catalysts is by taking a sheet of graphene and creating defects in it that they then fill with nickel. The defects define whether the atoms are in plane or stick out, which determines the rate of reaction.

Getting the defects at just the right size requires balancing between making them small enough so that it doesn’t disrupt the graphene, but large enough to accommodate the metal atoms.“There is an opportunity to lower the costs by designing conventional supports for single atom nickel,” Stavitski said.

At $6 a pound, nickel is considerably cheaper than platinum, which cost $150 a pound. Still, it is among the more expensive base metals.

“The single atom field is exploding,” he said. “Everyone is trying to develop this unique combination of support and metal that allows for the stabilization of single atoms. It’s very likely that we’re paving the way to a much larger adoption of this material in industry.”

Stavitski suggested that the field of electrocatalysts using nanomaterials has the potential to revolutionize industrial and commercial processes. The work he and his colleagues did with nickel, while compelling in its own right, is more of an evolutionary step, benefiting from some of the work that came before and finding a specific application that may become a part of a process that converts carbon dioxide into the energy-efficient carbon monoxide, while minimizing the production of an unwanted competing reaction.

The next set of experiments is to verify the same concept of graphene as a support for single atom catalyst, which can lead to a whole family of active and selective materials. Stavitski plans to explore combinations of metals, where he could link one metal to another to fine tune its electronic properties to develop metals that can target a wide spectrum of chemical reactions.

The work Stavitski is conducting with electrocatalysts is one of several areas he is exploring in his lab. He is also looking at developing types of batteries that are not based on lithium. 

With increased demand, primarily from electric vehicle manufacturing, lithium prices have “skyrocketed,” he explained in an email. “It’s important to develop batteries that employ sodium, which is cheap and abundant. Technologically, sodium batteries are much more difficult to deal with.”

Stavitski collaborates with a group at BNL led by Xiao-Qing Yang, who is the group leader for electrochemical energy storage.

Stacchiola has known Stavitski since 2010. He described him as “active and innovative” and suggested that this new capability of detecting single atoms in complex materials is “critical and is giving [Stavitski] significant growing exposure in the scientific community.”

Stacchiola appreciates how his colleague gets “fully immersed in every project he associates with.”

Stavitski grew up in the Soviet Union. After college, he moved to Israel and then the Netherlands. He arrived at BNL in 2010.

Currently a resident of South Setauket, Stavitski is married to Alena Stavitski, who works at BNL in the quality management office. The BNL couple have two sons who are 3 and 6 years old.

Stavitski, who speaks Russian, Hebrew and English, enjoys traveling.

As for his work, he is excited by the possibility of using the expanding field of nanomaterials to enhance the efficiency of commercial and energy-related processes.

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.

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.

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