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Power of 3

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Leemor Joshua-Tor. Photo from CSHL

By Daniel Dunaief

Like many of the other talented and driven professionals at Cold Spring Harbor Laboratory, Leemor Joshua-Tor often works far from the kind of spotlight that follows well-known actors or authors.

That changed in April and early May. First, the American Academy of Arts and Sciences elected her a member on April 11. Other members joining the academy this year include Carol Burnett, New York Times columnist Nicholas Kristof, actor Ian McKellen, who played Gandalf in the Hobbit films and Magneto in the X-Men movies, and Israeli writer David Grossman.

Then, on May 2, the National Science Foundation elected the Cold Spring Harbor Laboratory professor and Howard Hughes medical investigator to join its ranks. “I got a huge amount of congratulatory emails from many friends, some of which I haven’t been in touch with for a while,” Joshua-Tor said. “It’s humbling.”

Joshua-Tor’s research covers a range of areas in structural and molecular biology. She works with RNA interference, where she focuses on how small molecules regulate gene expression or translation. She has also worked with Cold Spring Harbor Laboratory President Bruce Stillman on the early stages of DNA replication.

Early this year, Joshua-Tor and Stillman published a paper in eLife Sciences in which they offered more details about the human origin recognition complex. Stillman suggested that Joshua-Tor was the “main driver” for the research, studying the structure of a protein he had isolated years ago. “I am not a structural biologist, but she is an outstanding one and together, we came up with a very satisfying result.”

The origin recognition complex begins the process of replication, recruiting a helicase, which unwinds DNA. It also brings in regulatory factors that ensure smooth timing and then other factors such as polymerase and a clamp that keeps the process flowing and ensures accurate copying of the genetic code. “We don’t know how ORC’s motor activity is used,” Joshua-Tor explained. “We don’t really know what it is on the DNA that the ORC likes to bind to.”

In the recent work, the scientists explored the ORC’s structure and tinkered with it biochemically to understand it. The ORC binds and hydrolyzes the energy molecule adenosine triphosphate, or ATP, in the same way a motor would, although it probably isn’t continuous. “It might use ATP hydrolysis to perform one sort of movement, perhaps a detachment,” Joshua-Tor suggested.

In the early stages of replication, ATP is necessary for the integrity of the ORC complex, as well as the helicase that gets recruited. “We knew from biochemistry that ORC bounds multiple ATP molecules, but we did not know precisely how,” Stillman explained in an email. “The structure told us. ORC does not open the DNA by itself, but loads a protein complex onto the DNA that, when activated, can open the DNA.” Stillman is working on that process now. The next step for the CSHL collaborators is to get a structure of human ORC bound to DNA.

In their recent work, the researchers characterized how mutations involved in ATP hydrolysis affect a condition called Meier-Gorlin syndrome. Of the mutations they characterized, one affects the ability to hydrolyze ATP. Patients with this syndrome have one copy of the gene with typical function and the other that doesn’t. This likely leaves the patient with half of the molecules to do the required job.

The misregulation of replication is often associated with cancer and is something Joshua-Tor and others consider when they conduct these studies.

ATP, meanwhile, is associated with all kinds of activities, including cell adhesion and taking down misfolded proteins. Many processes in the cell connect to these types of molecular machines.

In her research with RNA interference, she is studying how a microRNA called Let7 is produced. Let7 is involved in development. Before cells differentiate when they are stem cells, they make Let7 continuously and then destroy it. She is studying the pathway for this process. Let7 is absent from stem cells and in some cancers.

Interested in science and theater when she was young, Joshua-Tor grew up in Israel, where she participated in activities at the Weizmann Institute of Science. The institute has biology, biochemistry, chemistry, math, computer science and physics, as well as an archeology unit that didn’t exist when she was there. Later, when she was a graduate student, Joshua-Tor returned to the institute and became an instructor.

An important moment in her scientific development occurred when she was in seventh grade. She was learning about elements and she put each one on a card. She brought these cards to class to study them. Her mother gave her a container that had housed her perfumes, which created a positive association for chemistry every time she studied the elements.

Joshua-Tor was also interested in theater, where she was initially in shows and then became an assistant director. The researcher lives with her daughter Avery, who is 8 and attends the Jack Abrams Magnet School. The tandem have a Schnauzer named Charles Darwin. Her daughter is proud of her mother and tells “anyone that would listen” about the awards her mother recently won, Joshua-Tor said.

Joshua-Tor, whose lab now has 11 people, said she is excited for the opportunity to meet some of her fellow honorees this fall.

Stillman expressed pride in “all our scientists and especially when they make major discoveries and they receive such peer recognition,” he wrote in an email. Joshua-Tor is “one of our best, but we have many scientists who will go on to gain substantial peer recognition. This is her turn, at least for these two awards!”

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Fan Ye. Photo from SBU

By Daniel Dunaief

Fan Ye has a vision for the future filled with high service and efficiency that doesn’t involve butlers or personal attendants. The assistant professor of electrical and computer engineering in the College of Engineering and Applied Sciences at Stony Brook University is focused on creating smart environments in which window blinds open as people pull into their driveways, lights turn off in unoccupied rooms and the building guides a new student turn by turn through complex floors and hallways from entrance to the registrar’s office.

“The physical environment would be like a caring mother,” said Ye. It would sense and figure out people’s needs and “take care of the occupants inside the building.”

In Ye’s vision, which he estimates is about one year to decades away from a reality, objects that rely on people to turn them on or off, reposition them or alter their settings would have chips embedded in them, working together to create an environment that anticipates and learns in response to the need around it.

“With sensors, [a smart environment] can sense both physical conditions and human activities and adjust the environment in manners that create/improve comfort, safety, convenience” and the productivity of the occupant, he explained in an email.

Ye recently received a $450,000 award over the next five years from the National Science Foundation for early-career faculty for his study of smart environments. The prestigious award is the highest honor given by the government to scientists and engineers beginning their independent careers.

Initially, Ye is developing and testing a security system with the Stony Brook University Police Department and the Center of Excellence in Wireless and Information Technology that grants specific access to buildings or facilities depending on the specifications of an administrator.

Many of the buildings on campus have electric locks, which someone can open with a badge where there’s a badge reader. A badge, however “isn’t that flexible,” Ye said. If an administrator would like to grant someone one-time access to open a door that doesn’t provide ongoing access, that is difficult to do with a badge system.

“What’s lacking in this closed proprietary system is flexible access control, which can determine who has what access based on context factors,” he said. Ye, his team, the police department and the CEWIT are building a system that can enable greater flexibility that allows someone to open an office door for five minutes during a specific hour. “If any of these context factors is not satisfied, they don’t have access,” he said.

Ultimately, he would like to construct a system using modern mobile technology, like smartphones, instead of physical badges. The system would include embedded security that employs modern cryptography so a hacker or attacker can’t trick the system.

By using software and hardware security, Ye is hoping to develop a system that prevents the most common attacks at a reasonable cost, which he hopes would prevent someone from gaining access.

Ye is building real systems and testing them. The cost-benefit of these systems depends on the object. A motor to open and close a window would cost money to manufacture, install and operate. As with any technological innovation, he said, “the question comes down to, How do you invest versus how much do you get in return?”

Looking at the historical trend for computation resources, Ye said computing and storage costs are falling at an exponential rate, while the price for radio and sensing is also falling rapidly, although not at the same pace.

“I believe this trend will continue, especially for a lot of these objects that need small embedded systems” that can be manufactured at a scale with low cost, he continued. The process of turning the environment into an efficient, high-service system isn’t an all-or-nothing proposition. Consumers might decide to focus on the air-conditioning or heat use in their homes.

Other researchers are developing ways to harness the vibrational energy of movement or sound, which, conceivably, could power some of these electronics without requiring the delivery and consumption of more energy.

Ye recognizes that these parts can and will break down and require repair, just as dishwashers sometimes stop working and iPhones can lose a list of contacts. So many small electronic parts in a smart environment could seem like an invitation to malfunctions.

He likens the repair process to cloud computing, which allows small to medium-sized companies to rent computing resources from larger companies. “A smart environment, especially for public buildings like a university or office, could potentially run in a similar model,” he said. Individuals might rely on IT support from dedicated personnel who, like a superintendent in a building, could be responsible for a host of smart products.

A native of Hubei Province in China, Ye, who now lives in Setauket, loves to hike in national parks. His favorite is Canyonlands in Utah. Ye had worked at IBM for about 10 years before joining Stony Brook almost three years ago. While he was there, Ye worked on numerous projects, including distributed stream processing, cloud-based queueing and wide-area dependable messaging. “I learned tremendously at IBM,” he said.

Ye is “”well known and respected in the mobile and wireless computing research community,” Hui Lei, an IBM distinguished engineer, wrote in an email. “He conducted pioneering work on scalable message delivery, robust coverage and security in wireless sensor networks, which are well received and highly cited and closely related to the smart environment work he is doing now.”

Lei suggested that Ye’s experience and accomplishments provide him with a solid track record and he is “confident that [Ye] will be able to come up with innovative solutions in this area.”

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From left, Christopher Gobler with his research team Andrew Griffith, Theresa Hattenrath-Lehmann and Yoonja Kang. Photo from SBU

By Daniel Dunaief

Christopher Gobler searches the waters around Long Island for signs of trouble, which can appear starting in April. This year, he found it, in Shinnecock Bay. Monitoring for a toxin carried by algae called Alexandrium, Gobler recently discovered levels that were three times the allowable limit from the Food and Drug Administration. His finding, along with measurements from the New York State Department of Environmental Conservation of toxins in shellfish in the bay, have caused the recent closure of shellfishing in the bay for the fourth time in seven years.

While Gobler, a marine science professor at the School of Marine and Atmospheric Sciences at Stony Brook University, watches carefully for the appearance of red tides from these algae locally, he recently completed a much broader study on the spread of these toxins.

Gobler led a team that explored the effect of ocean warming on two types of algae, Alexandrium and Dinophysis. Since 1982, as the oceans have heated up, these algae have become increasingly common, particularly in the northern Atlantic and Pacific oceans, according to a study Gobler and his colleagues recently published in the Proceedings of the National Academy of Sciences. When they become concentrated in shellfish, these algae can lead to diarrhea, paralysis and even death if people consume enough of them.

Over the course of the study, algae have begun to form “denser populations that are making shellfish toxic,” Gobler said. Temperature is one of many factors that can affect the survival, growth and range of organisms like the algae that can accumulate toxins and create human illness. “As temperatures get higher, they are becoming closer to the ideal for some species and out of the ideal for other species,” Gobler said.

The strongest effect of changing temperatures are at higher latitudes, which were, up until recently, prohibitively cold for these types of algae. The biggest changes over the course of the study came in the Bay of Fundy in Canada, in Scotland, Ireland, Scandinavia, Iceland, Greenland and Alaska. The toxic algal blooms increased in frequency between 40 and 60 degrees north latitude, according to the study. These are places where toxic algae lived but weren’t as prevalent, but the warming trend has created a more hospitable environment, Gobler said.

Raphael Kudela, a professor of ocean sciences at the University of California, Santa Cruz who wasn’t involved in this research, explained that other papers have suggested a similar link between temperature and the movement of these algae. “We’ve seen the expansion of ciguatera fish poisoning, as the temperature range has moved poleward for those algae,” Kudela wrote in an email. NOAA biological oceanographer Stephanie Moore has documented an expanded window of opportunity for paralytic shellfish poisoning linked to changes in temperature, Kudela said. “While we can point to specific events, and it makes intuitive sense, the Gobler paper actually documented these trends using a long time series, which hasn’t been done before,” Kudela continued.

R. Wayne Litaker, a supervisory ecologist at NOAA’s National Ocean Service, collaborated with Gobler on the project. He said small differences in temperature are significant for the growth rate of these toxic algae. Extending this to other organisms, Litaker explained that fish are also extending their ranges amid a rise in global temperatures. “There’s been a general movement of temperate species toward the poles,” Litaker said. He’s seen tropical fish, such as butterfly fish, off the docks of North Carolina that he hadn’t seen that far north before.

Gobler and his colleagues estimate that the need to close shellfish beds, the increase in fish kills, and the health care damage to people has exceeded a billion dollars since 1982. The largest problem for people in areas like Alaska is their lack of experience with red tides.

“Communities are being exposed to these blooms where they had not been in the past,” Gobler said. “[The blooms] can be most dangerous when they take a community by surprise.” Gobler said this happened in Alaska during the study. In the last decade, shellfish toxins that are 1,000 times more potent than cyanide caused illnesses and were suspected in two deaths in Haines, Alaska.

Litaker said he gave a talk several years ago at a conference. Gobler approached him and asked if they could work together. “One of the wonderful things about these meetings is that you see things that trigger possibilities and whole new projects are born,” Litaker said.

Litaker described Gobler as a “major player in the field” who has done “fantastic work over the years.” Litaker said he was “quite impressed with what he’s done.” Litaker explained that the climate is changing and urged fisheries and shellfish experts to prepare to respond throughout the country. “As we get warmer and more run off of nutrients, toxic cyanobacteria [algal blooms] are causing problems in all 50 states,” Litaker said.

Kudela suggested that the “new records every year for the last several years … will undoubtedly continue to impact the range, duration and toxicity of blooms.”

Locally, Gobler continues to monitor dozens of sites on Long Island, where he suggested that Alexandrium could become less prevalent with warming, while Dinophysis could become more common. Temperature and other factors favorable for algae growth have led to red tides in the past.

In oceans across the world, Kudela said the next logical step would be to explore the interaction of temperature and nutrients. “We know both are changing, and they are likely to have additive or synergistic effects, but we haven’t done the same careful study as the Gobler paper looking at how the trends are interacting,” he explained.

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Student Giancarlos Llanos Romero will be joining the SBU team on a trip to Kenya this summer. Photo by Phoebe Fornof

By Daniel Dunaief

In a region known for the study of fossils left behind millions of years ago, a team of students from Stony Brook University’s College of Engineering and Applied Sciences is planning to travel to Kenya this summer to learn about and try to solve the challenges of today.

The university will send eight undergraduates to the Turkana Basin Institute for the engineering department’s first program in Kenya, which will run for over four weeks. In addition to classroom study, the students will seek opportunities to offer solutions to problems ranging from refrigeration, to energy production, to water purification.

The students learned about the opportunity in the spring, only a few months before they would travel to a country where the climate and standard of living for Kenyans present new challenges. “We were skeptical about how many students we would be able to get,” said Fotis Sotiropoulos, the dean of the College of Engineering and Applied Sciences, who “didn’t start marketing this” until after he took a trip to Kenya and the Turkana Basin Institute, which Stony Brook created at the direction of world-renowned anthropologist Richard Leakey.

Giancarlos Llanos Romero, who is interested in robotics and nanotechnology and is finishing his junior year, had originally planned to spend the summer seeking an internship in the Netherlands or Germany. When he learned about this opportunity, he immediately changed his focus. “I need to do this,” Romero said. “This is much more important than anything I could do in an internship.”

On first blush, the trip is anything but ideal for Romero, whose skin is sensitive to extreme heat, which he can expect to encounter in the sub-Saharan African country. He didn’t want that, however, to stop him and is planning to travel with seven other people he met for the first time last week. Romero said his immediate family, which is originally from Colombia, supported the trip.

Sotiropoulos, who is in his first year as dean, embraced the notion of connecting the engineering department with the Turkana Basin Institute. “Before I came here” said Sotiropoulos, “I felt very passionately about making sure that engineering students became familiar with the rest of the world” and that they understood global challenges, including issues like poverty and water scarcity.

Sotiropoulos met with TBI Director Lawrence Martin during one of his interviews prior to his arrival at SBU. Martin invited Sotiropoulos to visit with Richard Leakey, the founder of TBI whose family has been making scientific discoveries in Kenya for three generations.

Women and children in Kenya searching for, and drinking from, water found beneath the dry riverbed. Photo by Lynn Spinnato

This program quickly came together after those meetings. The two courses will teach students about design thinking, said Robert Kukta, the associate dean for undergraduate programs in the College of Engineering and Applied Sciences. Stony Brook would like to help students develop “the ability to think broadly about solutions and boil it down to the essence of the problem,” Kukta said. This, he said, will all occur in the context of a different culture and local resources.

Students will start their summer experience in Nairobi and then they will travel to Princeton University’s Mpala Research Centre, Martin said. “The journey through Kenyan towns opens visitors’ eyes tremendously to how different peoples’ lives are in different parts of the world,” Martin explained by email. “The goal is not so much to contribute immediately but to understand the challenges that people face, the resources available locally and then to improve their ability to think through possible solutions.”

Once students arrive at TBI, they will have an opportunity to see fossils from many time periods, including those from late Cretaceous dinosaurs. “Every visitor I have ever taken to TBI is amazed and in awe of the abundance of fossil evidence for past life on Earth,” Martin said.

A distinguished professor in the Department of Chemistry at SBU, Benjamin Hsiao, who traveled with Sotiropoulos to Kenya in the spring, is a co-founding director of Innovative Global Energy Solutions Center. Hsiao has been developing water filtration systems through IGESC, which brings together TBI with universities, industry, international governments and foundations. He is well acquainted with the challenges the first set of students will face.

“Once we bring technologies over to Kenya, [sometimes] they do not work for reasons we have not thought of,” which include dust or a broken part for which it’s difficult to find a replacement, he said. “Those failed experiments give us tremendous insight about how to design the next-generation systems which will be much more robust and sustainable and easier to operate by local people.”

Acacia Leakey, who grew up in Kenya and is Richard Leakey’s grandniece, recently completed her senior design project as an undergraduate at Stony Brook. Her work is intended to help farmers extend the life of their tomato plants when they bring them to market.

About 32 percent of the tomatoes go to waste from the extreme heat. Acacia and her team developed a vegetable cooler that employs solar panels to reduce the temperature from 32 degrees Celsius to 15 degrees Celsius, which should extend the life of the tomatoes. Her classmates were “surprisingly supportive” of her work, she said, as some of them hadn’t considered applying their skills in a developing country.

Leakey, who will train for her master’s degree at Stony Brook this fall, will continue to provide insights into Madagascar, another developing African nation where the university has an internationally acclaimed research center. This summer, she will produce a video that will record information from villages near Centre ValBio in Madagascar, which she will bring back to Stony Brook in the hopes of encouraging others to use that information to create their own design projects next year.

As for Romero, who is raising money for the trip through a GoFundMe page, he is prepared to discover opportunities amid the challenges of his upcoming trip and is eager “to be able to actually help a community and say I left a mark.”

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Patricia Wright speaks at the Earth Optimism Summit in April. Photo by Ronda Ann Gregorio

By Daniel Dunaief

Determined to share success stories instead of doom and gloom, Nancy Knowlton, the Sant Chair of Marine Science at the Smithsonian Institution’s National Museum of Natural History, decided to change the tone of the conservation dialog.

Knowlton organized the first Earth Optimism Summit around the most recent Earth Day this April. She searched for speakers who could share their progress and blueprints for success. That included Patricia Wright, a Stony Brook University distinguished professor who has developed an impressive legacy during her 25 years in Madagascar.

Nancy Knowlton, organizer of the first Earth Optimism Summit in April. Photo by Ronda Ann Gregorio

In Madagascar, the 10th poorest country on Earth, optimism has been growing, perhaps even more rapidly than the 1,000 endemic trees that have been making a comeback in the island nation off the southeast coast of Africa. The growth of those trees has encouraged the return of animals that had retreated from an area thinned out by selective logging.

“This year, the rare and furtive bird, the scaly ground roller, came back and nested,” Wright reported. The “black and white ruffed lemur gave the area the thumbs up and reestablished territories and reproduced.”

The critically endangered golden bamboo lemur also doubled the size of its population. “The forest took 25 years to recover, but it can recover,” Wright said in her speech. Dedicated to the study of lemurs, Wright in 1991 helped create Ranomafana National Park, which is the third largest park in Madagascar. She served as a plenary speaker for a gathering that drew over 1,400 people to Washington. Scientists and policymakers held sister summits in nine other countries at the same time.

“You can’t possibly make progress in conservation if you only talk about the problems,” said Knowlton, a co-host of the summit. Knowlton knew Wright from serving on the Committee for Research and Exploration, where the two interacted six times a year. When she was putting together the list of speakers, Knowlton approached the 2014 winner of the Indianapolis Zoo Prize to see if she could share a positive message in conservation.

When Wright accepted, Knowlton was “thrilled, not only because she’s a good storyteller, but because she’s also done incredibly important work in Madagascar.” Indeed, Wright said national parks have greatly expanded from only two in the 1980s. “Now with the work of many dedicated environmentalists, including the enlightened policy of the U.S. government through USAID, we have 18 National Parks and a National Park Service to manage and protect them,” she told the session.

Restoring trees to the area also offers economic opportunity, Wright said. Under the endemic trees, farmers can grow crops like vanilla, chocolate, cinnamon and wild pepper, she said. “All these products can be marketed for high prices. We will take back that land and make it productive again, doubling or tripling its value,” Wright continued.

A scientist featured in the 2014 film “Island of Lemurs: Madagascar,” Wright has engaged in a wide range of efforts on behalf of the Malagasy. Last year, she negotiated with a mayor on the island to pick up trash in exchange for the purchase of several wheelbarrows. She also helped encourage the renovation of 35 schools in communities around Ranomafana, where students learn critical thinking and molecular biology. This, Wright said, is occurring in a country where three out of five students don’t remain in school past fifth grade. “More children in this region are graduating from high school and over a handful have received university degrees,” she explained.

A health team also walks to 50 nearby villages, carrying medicines and basic health lessons. SBU brought drones last year, which can fly medicines as far as 40 miles away. Drones could monitor the outbreak of any unknown and potentially dangerous disease and can offer health care for people who live in ares that are inaccessible by road.

The financial support of the National Science Foundation helped create Centre ValBio, a field station and campus in the middle of the rainforest. The research station has modern facilities and equipment to conduct genetics and disease analyses. “We provide tools and training and even fiber-optic cable internet, the fastest in the region,” Wright said. They are expanding the research facilities this year.

Through research efforts, Wright and other scientists have also discovered two new species of lemurs and found two others that were considered extinct. Restoring the national forest not only brought back animals that had retreated into the inner part of the forest, but it also encouraged the growth of ecotourism.

In 1991, there was only one tourist hotel and now there are 32 hotels, providing facilities for the 30,000 tourists. “That can start to change an economy,” Wright suggested. “Cottage industries have developed like the woman’s weaving group and the basket weavers and blacksmiths who all make a good living from selling to tourists and researchers.”

Wright attributes these positive steps to a dedication to working with residents in the area. “We have been successful by training local residents and university students, by listening to what the communities want, rather than what we think is best,” she said.

Knowlton suggested that “you can’t helicopter conservation into a particular place. It’s got to be built from the ground up. She’s done it in Madagascar.” While these are positive steps, Wright declared this is just the beginning. “There are endless possibilities of scientific knowledge and research,” she said. “They all matter and impact our daily lives.”

As for the Earth Optimism Summit, Knowlton said this is just the beginning as well, originally thinking of organizing a second summit in 2020, but may hold the next one sooner. “We’re identifying what’s working and putting a spotlight on it,” Knowlton said. “The feedback has been extraordinarily, unbelievably positive. We’ve come to realize that people are demanding” another conference.

She appreciated Wright’s contribution to April’s conference.“By sharing her successes, Pat Wright brings home the message that if she can do it, so can we all,” Knowlton said. “The summit succeeded because Wright and over 240 other speakers made it obvious, through the successes that they shared, that solving the environmental problems we face is not out of reach.”

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Escobar-Hoyos, center, holds her recent award, with Kenneth Shroyer, the chairman of the Department of Pathology at Stony Brook on the left and Steven Leach, the director of the David M. Rubenstein Center for Pancreatic Cancer Research on the right. Photo by Cindy Leiton

By Daniel Dunaief

While winter storm Niko in February closed schools and businesses and brought considerable precipitation to the region, it also coincided with great news for Luisa Escobar-Hoyos, who earned her doctorate from Stony Brook University.

Escobar-Hoyos, who is a part-time research assistant professor in the Department of Pathology at Stony Brook University and a postdoctoral fellow at Memorial Sloan Kettering Cancer Center, received word that she was the sole researcher selected in the country to receive the prestigious $600,000 Pancreatic Cancer Action Network–American Association for Cancer Research Pathway to Leadership Award.

When she heard the news, Escobar-Hoyos said she was “filled with excitement.” After she spoke with her husband Nicolas Hernandez and her current mentor at MSKCC, Steven Leach, the director of the David M. Rubenstein Center for Pancreatic Cancer Research, she called her parents in her native Colombia.

Her mother, Luz Hoyos, understood her excitement not only as a parent but as a cancer researcher herself. “My interest in cancer research started because of my mom,” Escobar-Hoyos said. Observing her example and “the excitement and the impact she has on her students and young scientists working with her, I could see myself” following in her footsteps.

The researcher said her joy at winning the award has blended with “a sense of responsibility” to the growing community of patients and their families who have developed a deadly disease that is projected to become the second leading cause of cancer-related death by 2020, according to the Pancreatic Cancer Action Network, moving past colorectal cancer.

The Pancreatic Cancer Action Network has awarded $35 million in funding to 142 scientists across the country from 2003 to 2016, many of whom have continued to improve an understanding of this insidious form of cancer.

David Tuveson, the current director of the Cancer Center at Cold Spring Harbor Laboratory, received funds from PanCan to develop the first genetically engineered mouse model that mimics human disease. Jiyoung Ahn, the associate director of the NYU Cancer Institute, used the funds to discover that two species of oral bacteria are associated with an over 50 percent increased risk of pancreatic cancer.

Over the first decade since PanCan started awarding these grants, the recipients have been able to convert each dollar granted into $8.28 in further pancreatic cancer research funding.

In her research, Escobar-Hoyos suggests that alternative splicing, or splitting up messenger RNA at different locations to create different versions of the same protein, plays an important part in the start and progress of pancreatic cancer. “Her preliminary data suggest that alternative splicing could be associated with poorer survival and resistance to treatment,” Lynn Matrisian, the chief science officer at PanCan, explained in an email. “The completion of her project will enhance our understanding of this molecular modification and how it impacts pancreatic cancer cell growth, survival and the progression to more advanced stages of this disease.”

Escobar-Hoyos explained that she will evaluate how mutations in transcriptional regulators and mRNA splicing factors influence gene expression and alternative splicing of mRNAs to promote the disease and aggression of the most common form of pancreatic cancer. Later, she will evaluate how splicing regulators and alternatively spliced genes enriched in pancreatic ductal adenocarcinoma contribute to tumor maintenance and resistance to therapy.

Escobar-Hoyos will receive $75,000 in each of the first two years of the award to pay for a salary or a technician, during a mentored phase of the award. After those two years, she will receive $150,000 for three years, when PanCan expects her to be in an independent research position.

Escobar-Hoyos said her graduate research at Stony Brook focused on ways to understand the biological differences between patients diagnosed with the same cancer type. She helped discover the way a keratin protein called K17 entered the nucleus and brought another protein into the cytoplasm, making one type of tumor more aggressive.

While Escobar-Hoyos works full time at Memorial Sloan Kettering, she continues to play an active role in Kenneth Shroyer’s lab, where she conducted experiments for her doctorate. She is the co-director of the Pathology Translational Research Laboratory, leading studies that are focused on pancreatic cancer biomarkers. The chair in the Department of Pathology, Shroyer extended an offer for her to continue to address the research questions her work addressed after she started her postdoctoral fellowship.

“When you do research projects and you develop them from the beginning, they are like babies and you really want to see how they evolve,” Escobar-Hoyos said. Numerous projects are devoted to different aspects of K17, she said.

Shroyer said Escobar-Hoyos had already been the first author on two landmark studies related to the discovery and validation of K17 even before her work with pancreatic cancer. “She has also conducted highly significant new research” that she is currently developing “that I believe will transform the field of pancreatic cancer research,” Shroyer wrote in an email.

Shroyer hopes to recruit Escobar-Hoyos to return to Stony Brook when she completes her fellowship to a full-time position as a tenure track assistant professor. “Based on her achievements in basic research and her passion to translate her findings to improve the care of patients with pancreatic cancer, I have no doubt she is one of the most promising young pancreatic cancer research scientists of her generation,” he continued.

Yusuf Hannun, the director of the Stony Brook Cancer Center, said Escobar-Hoyos’s work provided a new and important angle with considerable promise in understanding pancreatic cancer. “She is a tremendous example of success for junior investigators,” Hannun wrote in an email.

Escobar-Hoyos said she is hoping, a year or two from now, to transition to becoming an independent scientist and principal investigator, ideally at an academic institution. “Because of my strong ties with Stony Brook and all the effort the institution is investing in pancreatic research” SBU is currently her first choice.

Escobar-Hoyos is pleased that she was able to give back to the Pancreatic Cancer Action Network when she and a team of other friends and family helped raise about $4,000 as a part of a PurpleStride 5K walk in Prospect Park earlier this month.“I was paying forward what this foundation has done for me in my career,” she said.

Matrisian said dedicated scientists offer hope to patients and their families. “Researchers like Escobar-Hoyos spark scientific breakthroughs that may create treatments and ultimately, improve the lives of patients,” she suggested.

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Ride For Life presents CSHL with $300,000 for ALS research: from left, CSHL Director of Annual Giving and Donor Relations Karen Orzel, CSHL Assistant Professor Molly Hammell, Ride for Life Founder Chris Pendergast, Stony Brook Associate Professor Josh Dubnau and Ride for Life board member Frank Verdone. Photo by Jessa Giordano, Cold Spring Harbor Laboratory

By Daniel Dunaief

The past can come back to haunt us, even in the world of genetics. Over the course of millions of years, plants and animals have battled against viruses, some of which inserted their genes into the host. Through those genetic struggles, explained Molly Hammell, an assistant professor at Cold Spring Harbor Laboratory, cells develop “elaborate ways to fight back,” even as they continue to make copies of these pieces of DNA.

Sometimes, when our defenses break down, these retrotransposons, or jumping genes, can become active again. Indeed, that appears to be the case in a fly model of amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease.

Working on a fruit fly model of ALS, Joshua Dubnau, an associate professor at Stony Brook University, Lisa Krug, who earned her doctorate at Cold Spring Harbor Laboratory and is now working at Kallyope in New York, and Hammell showed that these ancient genetic invaders play an important role in the disease amid activation by a protein often linked to ALS called TDP-43.

A recent study, published in PLOS Genetics, “really proves that retroviral reactivation (as a consequence of TDP-activity) is … central to either causing or accelerating neuronal cell death when TDP-43 inclusions are present,” explained Hammell in an email. If TDP-43 plays the same role for humans, this would suggest that targeting this protein or the jumping genes, it activates could lead to potential treatment for ALS.

These collaborators showed that an aggregation of this protein turned on jumping genes. These genes can make copies of themselves and insert themselves in other parts of the genetic code. In this case, TDP-43 expression disrupts the normal immune-like system that silences retrotransposons such as gypsy, which is a particular type of jumping gene in the fruit fly.

When gypsy was activated, the fruit fly exhibited many of the features of ALS, including protein pathology, problems with movement, shortened life span and cell death or glia and neurons in the brain. The scientists were also able to turn gypsy off, which improved the health and extended the life span of the fly.

Mimicking this protein results in broad activation of several retrotransposons. If this also occurs in people, the disease may activate a retrotransposon that is the human analog to gypsy, called HERV-K, as well as other retrotransposons. The study also suggests that DNA damage caused by retrotransposons may active a cell suicide mechanism. Finally, this effort showed a means by which the protein disrupts the normal immune surveillance that keeps retrotransposons quiet.

To be sure, Dubnau cautioned that animal models of a disease may not translate when returning to people. Researchers need to look at more patients at all the retrotransposons in the human genome to monitor its prevalence, Dubnau suggested. If the link between retrotransposon activation and the development of ALS is as evident in humans as it is in the fruit fly, scientists may take an approach similar to that which they took to battle the human immuno-deficiency virus, or HIV. Retrotransposons have an RNA genome that needs to be copied to DNA. This, Dubnau explained, is the step in the process where researchers attacked the virus.

In a small subset of HIV patients who have motor neuron symptoms that are similar to ALS, Avi Nath, a senior investigator at the National Institutes of Health discovered that treating patients with the typical HIV medication cocktail helped relieve their ALS symptoms as well.

“What is not known is whether, for some reason, this subset of patients had an ALS syndrome caused by HIV or they were curing them” by treating HIV, Dubnau said. Nath is currently involved in one of two clinical trials to see if HIV medications help ALS patients. The next step for Dubnau and Hammell is to screen the tissue of numerous ALS patients after their death to see if their retrotransposons were elevated.

In addition to NIH funding, the scientists received financial support from Ride for Life, which is a not-for-profit organization started in 1997 that raises funds for research to find a cure for ALS, supports patients and their families through patient services and raises awareness of ALS. Every May, Ride for Life conducts a 12-day, 100-mile patient wheelchair ride across Long Island. Dubnau and Hammell, who received a $300,000 grant from Ride for Life in 2015, said they have been inspired by Ride for Life founder Chris Pendergast.

Meeting Pendergast “has had a big impact,” Dubnau said. “He’s a force of nature. He’s an incredibly strong and intelligent person.” Receiving funds from Ride for Life created a sense of personal obligation to Pendergast and many other people who “had raised that money through sweat and effort.”

Without funding from the Ride for Life Foundation, “We would not have the resources to obtain these samples and do the sequencing experiments necessary to prove that this is a clinically relevant phenomenon in a large number of ALS patients,” Hammell said.

Through an email, Pendergast explained that Ride for Life chose to fund the work by Dubnau and Hammell because the research met several criteria, including that it might lead to new strategies to treat ALS and the research was on Long Island, which is a “powerful affirmation for our generous donors.”

Pendergast emphasized the importance of funding basic ALS research. “We need to know why it develops, how it progresses [and] how it can be diagnosed and monitored,” he urged.

A resident of Huntington, Dubnau and his wife Nicole Maher, who works at the Nature Conservancy as a climate scientist, have a nine-year-old daughter, Caitlin. Reflecting both of her parents’ professional interests, Caitlin is going to a statewide science fair, where she is presenting her work on how temperature affects the life span of insects.

As for his research, Dubnau hopes a further exploration of TDP-43 might reveal an important step in the progression of ALS. He hopes this discovery may suggest a strategy researchers and clinicians can take that might “stop the cascade of events” in ALS.

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Percy Zahl. Photo courtesy of BNL

By Daniel Dunaief

When he was in high school in Negenborn, Germany, Percy Zahl built his own computer, with some help from one of his father’s friends. Nowadays, Zahl spends considerable time improving the computer capability of an open-source community drive software project that helps researchers see structures and interactions at a subatomic level.

Recently, Zahl, who is an associate scientist in the Proximal Probe Microscopy facility at the Center for Functional Nanomaterials at Brookhaven National Laboratory, completed an extensive upgrade to software called Gnome X Scanning Microscopy, or GXSM, that adds a whole suite of new features. Zahl re-coded about half of the original 300,000 lines of code during this project.

The software, which is used to operate any kind of scanning probe microscopy system which includes atomic force microscopy and scanning tunneling microscopy, has a wide range of applications, from understanding catalysts that facilitate chemical reactions, to capturing gases, to biomedical sensors.

Oliver Monti, a professor of chemistry and biochemistry and a professor of physics at the University of Arizona, has been working with Zahl for over four years and has been using this system to explore atomic and molecular-scale processes that determine efficiency in plastic solar cells and other next-generation low-energy-use technologies. He said he uses the GXSM for data analysis.

Zahl “often introduces modifications and upgrades as instantaneous response to some scientific need,” which has “helped us solve specific problems efficiently,” Monti explained in an email. A former student of Monti’s needed to analyze molecule-to-molecule interactions. The two came up with an algorithm to study that and, unprompted, Zahl “introduced a version of this algorithm to his software.”

Percy Zahl (front of line) during a Tour of Somerville race in 2011. Photo by Anthony Skorochod.

Monti said he is “very much aware of the most recent release,” which he considers a “major upgrade” and he is in the process of installing it. The new software allows the export of images in formats such as PDF and SVG, which are editable and resolution independent, Zahl explained. A PDF output of a graph has publication quality, while the images with high-resolution displays are enhanced and sharper than the previous bitmap PNG files.

The upgrade also includes making a remote control process for automating scanning and manipulation tasks “easy to use,” which is a “big plus for less experienced users,” Zahl explained. It can help automate complex or tedious repetitive jobs. As an example, Zahl said the need to scan an image that takes 10 minutes each for 20 different settings creates a laborious task. “I can either sit there and enter manually a new number every 10 minutes” or he can program a script that he made to use a list of bias voltages and hit execute in the new remote console, he explained, leaving him time to work on other projects for the next two hours and 20 minutes.

Recently, Zahl ran a spectra covering the area of a molecule, which is a task he can do reliably without worrying about user typos or errors. An additional noncontact atomic force microscopy simulation plug-in module provides researchers with a more efficient way to generate data. The new approach measures the force between atoms and molecules of the surface of a sample and a probe smaller than the diameter of an atom. Zahl has calculated and simulated forces between atoms, taking into account all atoms of a molecule and the probe atom and finds the equilibrium position of his probe. Using that three-dimensional force field, he can extract an image that he compares to the model.

Zahl spends about three quarters of his time working with users like Monti, while he dedicates the remaining time to his own projects. He appreciates the opportunity to work with many different systems and with people in a wide range of scientific disciplines.

“It’s really as diverse as it can get in this particular field of fundamental surface science — a specialty of solid state physics,” Zahl explained in an email. He has the experience to work with many different sample types while still continuing to learn “all the tricks on how to get the best images possible.”

Monti appreciates Zahl’s dedication to his work. “Data processing and analysis can be challenging,” he explained. His students often compare a trip to BNL to drinking from a firehose.

Zahl has been “essential in helping us figure out how to sift through the data and quickly focus on the most important observations,” Monti added. That appreciation extends well beyond Monti’s lab. “Whenever I meet colleagues across the world who had the pleasure to interact with [Zahl], they lavish praise on his scientific and technical expertise,” Monti said.

Bruce Koel, a professor in the Department of Chemical and Biological Engineering at Princeton University, appreciated Zahl’s contribution to his research on chemical reactions at surfaces. Zahl has “enabled us to do very high impact research,” Koel explained in an email. This work would “not have been possible without [Zahl’s] technical support and guidance about what experiments could be done.”

A resident of Rocky Point, Zahl rides the 20 miles to work as often as he can on one of several of his bicycles. An avid cyclist, Zahl has a high-end racing bike, a commuter bike and a mountain bike from those “beloved times” riding mountain trails in Switzerland.

In Chile, he reached a top speed of around 56 miles per hour descending the Osorno Volcano. In a YouTube video of his ride, he can be seen passing a car in a clearing along the windy road.

As for his work, Zahl remains committed to continuing to improve the software scientists use to enhance their visual understanding of the small surfaces of the substances they study. “I am pretty much always working on some new details or fixing this and that tiny issue,” he said. “No software is ever done. It’s evolving.”

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Jun Wang in her laboratory with a transmission x-ray microscope. Photo from BNL

By Daniel Dunaief

The first time is most definitely not the charm. That’s what Jun Wang and her colleagues at Brookhaven National Laboratory discovered about sodium ion batteries.

Wang, a physicist and lead scientist at the facility, looked deep into the inner workings of a sodium ion battery to determine what causes structural defects as the battery functions. As it turns out, the first time a sodium ion battery charges and discharges, it develops changes in the microstructure and chemical composition of iron sulfide. These changes, which degrade the performance of the battery, are irreversible during the first charging cycle.

“We found that the cracks happened during the first cycle, then, after that, the structure kind of reached equilibrium,” said Wang, who published her research in the journal Advanced Energy Materials. “All these changes happen during the first cycle.”

Collaborators from Brookhaven’s Photon Sciences and Sustainable Energy Technologies groups stand behind the new transmission x-ray microscope (TXM) at BNL’s National Synchrotron Light Source. From left: Yu-chen Karen Chen-Wiegart, Can Erdonmez, Jun Wang (team leader), and Christopher Eng. Photo from BNL

Sodium ion batteries are considered an alternative to lithium ion batteries, which are typically found in most consumer electronics. Like lithium, sodium is an alkali metal, which means that it is in the same group in the periodic table. Sodium, however, is more abundant and, as a result, considerably less expensive than lithium.

Using a synchrotron-based hard X-ray full-field microscope, Wang was able to see what happened when sodium ions moved into and out of an iron sulfide electrode through 10 cycles. “We can see this microstructure evolution,” she said.

Wang monitored the evolution as a function of time while the battery is charging and discharging. The results are the first time anyone has studied a sodium-metal sulfide battery with these tools, which provides information that isn’t available through other methods. “It is challenging to prepare a working sodium ion battery for the in operandi/in situ TXM study to correlate the microstructural evolution with its electrochemical performance,” she said.

Other researchers suggested that Wang has developed a following in the scientific community for her ground-breaking research. “She has a very good reputation in the area of X-ray nanotomography, applied to a wide range of different materials,” Scott Barnett, a professor of materials science and engineering at Northwestern University, explained in an email. “I am most familiar with her work on fuel cell and battery electrodes — I think it is fair to say that this work has been some of the best pioneering research in this area,” he said.

Barnett, who started collaborating with Wang in 2010 on measuring fuel cell and battery electrodes with X-ray tomography, suggested that Wang’s work on capacity loss “could certainly lead to new breakthroughs in improved batteries.”

In her most recent work with sodium ion batteries, Wang found that the defects start at the surface of the iron sulfide particles and move inward toward the core, Wang said. The microstructure changes during the first cycle and is more severe during sodiation. The particles don’t return to their original volume and shape. After the first cycle, the particles reach a structural equilibrium with no further significant morphological changes, she said.

In other cycles, the material does not show further significant morphological changes, reach a structural equilibrium and electrochemical reversibility. Wang and her colleagues confirmed these observations with X-ray nanotomography, which creates a three-dimensional image of the battery material while recording the change in volume.

Wang suggested that a way to reduce these structural defects could be to reduce the size of the iron sulfide particles to create a one-phase reaction. She will work with other collaborators on modeling and simulations that will enhance the design of future battery materials.

In addition to conducting research on batteries, Wang is an industrial program coordinator in the Photon Science Directorate at BNL. She works with industrial researchers and beamline staff to find and explore new opportunities in industrial applications using synchrotron radiation. She leads the industrial research program, interacting with user groups through consultation, collaboration and outreach.

To manage her research, which includes a lab of three other researchers, and to accomplish her mission as manager of an industrial research program, Wang jokes that she “spends 100 percent of her time” with each responsibility. “I try to do my best for the different things” she needs to do with her time, she said.

Jun Wang with her husband Qun Shen and their 11-year old son Sam in Waikiki last year. Photo from Jun Wang

A native of Wuhu, China, Wang earned her bachelor’s degree in physics from Anhui University in China and her doctorate in physics from the Chinese Academy of Sciences in Beijing. She worked at the Beijing Synchrotron Radiation Facility, which was the first synchrotron light source in China. During her doctoral training, she studied multilayer films using X-ray diffraction and scattering.

A resident of Poquott, Wang is married to Qun Shen, who is the deputy director for science at the NSLS-II. The couple has an 11-year-old son, Sam, who is a sixth-grade student at Setauket Elementary School. Shen and Wang met at an international X-ray crystallography conference in the early 1990s.

Shen trained in the United States after he graduated from Beijing University in 1980, when he went to Purdue University for his doctorate through the China-US Physica Examination and Application Program. The couple have worked together a few times over the years, including publishing a paper in Nature Communications. Wang is hoping that her work with battery research will lead to improvements in the manufacture and design of sodium ion batteries.

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Above, members of the New York Chapter of The Children’s Heart Foundation present CSHL Research Assistant Professor Michael Ronemus with a $50,000 check from The Children’s Heart Foundation for his recently funded research grant on Feb. 23. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

By Daniel Dunaief

Just before he took a holiday break in December, Michael Ronemus received a welcome surprise. “In the last afternoon before the holidays, I got a call from William Foley. He said, ‘Congratulations,’” recalled Ronemus, a research assistant professor at Cold Spring Harbor Laboratory. “I submitted the application in May and I didn’t know what to expect.”

Foley, the executive director at the Children’s Heart Foundation, was reaching out to Ronemus to let him know he was one of seven researchers — six in North America and one in Europe — to receive funding for his research. Ronemus received a check for $50,000 at a presentation ceremony on Feb. 23.

Scientists are seeking out private foundations more as they search for sources of funding, said Ronemus. The funds will help Ronemus use next-generation sequencing to look closely at 120 families for evidence of copy number variation in their genes.

 

When a person has a different number of copies of a part of a specific gene, that can be a positive, neutral or negative event, depending on the consequence for the individual. Most copy number variations are neutral, which is why people have hundreds of them in their genes. Copy number variations can contribute, however, to de novo mutations, presenting changes in a genetic code that can make the genes of an offspring different from those of his or her parents. If these mutations damage a gene that’s essential for normal development of the heart, they can contribute to congenital heart defects.

Michael Ronemus explains the relevance of his research to the community at the check presentation event on Feb. 23. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

Indeed, the Children’s Heart Foundation has contributed $8.7 million to research, hoping to improve the ability to prevent, diagnose and treat the 40,000 people born each year in the United States with a heart defect. Of the children born with a heart defect, about one in four, has a form of critical congenital heart disease, said Jon Kaltman, the chief in the Heart Development and Structures Diseases Branch of the National Heart, Lung and Blood Institute. That means he or she will most likely require surgery within the first year of life, although most have it within the first month.

At this point, doctors and researchers understand the genetic cause of congenital heart disease for a small percent of people. The work of the Pediatric Cardiac Genomics Consortium hopes to make this true for a larger number of people with a congenital heart defect, Kaltman said.

Knowing the genetics of a patient and his or her family could be “helpful for that family to understand what might have caused the congenital heart disease” said Kaltman, who has been a pediatric cardiologist since 2005. “If that family were to have another child” the genetics could help assess the “risk that a second child will also have a congenital heart defect.”

A greater awareness of the genes involved in heart disease could also provide a guide for the way the defect might react to treatment. “We see patients with identical looking hearts [on an echocardiogram] from different families in which they undergo surgery” and have different reactions, Kaltman said. “One does well and has few complications and the other develops arrhythmias at 15 and heart failure at 25.”

The differences in respones to treatment for those patients may be genetic. “For the patient with the genetic signal for the complicated course, we can do more interventions early on,” Kaltman said, which could include earlier valve replacements or more aggressive arrhythmia surveillance.

Working with Bruce Gelb, a professor in pediatrics and cardiology at Mount Sinai Hospital, Ronemus is focusing on a group of patients with a condition called tetralogy of Fallot. Children with this defect develop a bluish color in their skin and can have trouble breathing when they exercise.

New York Chapter president of the Children’s Heart Foundation Jackie Pecora speaks at the check presentation event. Photo courtesy of ©C. Brukin, 2017/Cold Spring Harbor Laboratory

Doctors treat people with this condition with open heart surgery, which fixes a hole between the ventricles and opens up a narrowed right ventricular outflow tract. “Early diagnosis can lead to a straightforward procedure and good outcome,” Ronemus said. “If there is any reason to suspect [that a developing fetus has this condition], we’d like to know.”

By studying copy number variation, Gelb and Ronemus can search for signatures or markers in prenatal screening, which doctors can do through amniocentesis or cell-free fetal DNA analysis, which is a noninvasive form of prenatal testing. A definitive diagnosis even before birth could help doctors prepare for quick intervention that could be more effective, Ronemus said. If not diagnosed, a third of the children with the condition die within the first year and 50 percent in the first three years, Ronemus explained. If doctors know a child has the condition, they can take precautions, like have supplementary oxygen or drugs nearby.

Ronemus, who started his career in plant genetics and then became involved in the study of autism, is applying a genetic technique he co-developed at CSHL for copy number variation detection called SMASH. He applied for the Children’s Heart Foundation grant because of a meeting at CSHL with Jackie Pecora, a resident of East Northport, who is New York Chapter president of the Children’s Heart Foundation. The foundation has 11 chapters throughout the country and raises funds through events like the Long Island Congenital Heart Walk, which will take place on May 21 in Sunken Meadow State Park. Ronemus will be an honorary co-chair for the walk.

Foley said Ronemus’ approach is a “unique way” of looking at congenital heart defects. During the medical advisory board’s discussion of which projects to fund “there was a lot of enthusiasm” for this project. Ronemus is the first New York researcher to receive CHF funds since 2009.

A resident of East Meadow, Ronemus lives with his wife Ana Rodriguez-Fernandez, who is an associate professor of microbiology at the NYU School of Medicine. The couple has three children, Martin, 14, Silvia, 12, and Daniel, 11.

Pecora has family experience with congenital heart disease. After she gave birth to twins 18 years ago, doctors discovered that her daughter Chloe had a heart defect that required surgery. Nine days after she was born, Chloe died from an infection. Pecora got involved because of a bumper sticker for another grassroots fundraiser for a baby with the same heart condition as Chloe. That led her to the Children’s Heart Foundation. While the awareness among the public is improving, there’s still a way to go to combat a prevalent condition, Pecora said. “Look at the clock: Every 15 minutes a baby is born with congenital heart disease. People don’t realize the magnitude.”

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