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At the first meeting of the HiTOP consortium. Kotov is in the center. Photo from HiTOP consortium.

By Daniel Dunaief

Instead of lamenting the shortcomings of a system they felt didn’t work as well as it should, Roman Kotov and a growing group of collaborators whose numbers now exceed 50 decided to do something about it. An associate professor of psychiatry at Stony Brook University, Kotov and his collaborators are building their own mental health tool, which, they hope, will offer specific diagnoses for everything from anxiety to schizophrenia.

Roman Kotov. Photo from SBU School of Medicine

The current resource psychologists and psychiatrists use is called the “Diagnostic and Statistical Manual of Mental Disorders 5,” which came out in 2013. The latest version of the DSM, as the manual that offers psychologists and psychiatrists a way to link a collection of symptoms to a diagnosis is called, “felt far too limited,” Kotov said. “Once we started discussing [an alternative], almost everyone was interested in the scientific community. They thought it was a good and necessary idea.”

Called the Hierarchical Taxonomy of Psychopathology, or HiTOP, the developing classification system uses scientific evidence, illness symptoms and impaired functioning in its diagnoses. Another HiTOP co-creator, David Watson, the Andrew J. McKenna Family professor of psychology at the University of Notre Dame, recognized Kotov’s important early work on the project.

Kotov “deserves sole credit for the idea of putting all of our data together to provide the basis for an alternative model,” Watson explained in an email. “He did some preliminary work along these lines, which convinced us that this was a great idea that was worth pursuing.” Watson, who served as Kotov’s graduate adviser at the University of Iowa, said that his former student leads meetings and conference calls for the HiTOP group.

The HiTOP system, which was recently described in the Journal of Abnormal Psychology, views mental disorders along a spectra, while also using empirical evidence to understand overlap among disorders and classify different symptoms within a given diagnosis. As an example, Kotov said that depression in the DSM is “treated as one thing. We know that depression is heterogeneous.”

Indeed, some people with depression may have lost their appetite and have trouble sleeping, while others may be eating and sleeping considerably more than they would if they weren’t depressed. “In some ways, these are opposite presentations, yet they get the same diagnosis” in the DSM, Kotov said.

HiTOP unpacks this variability into seven dimensions, which describe symptom types. That is helpful not only for a diagnosis but also for a treatment. HiTOP also goes beyond the binary description of the presence or absence of a particular symptom, offering clinicians a way of indicating the severity of a problem. At this point, HiTOP is a developing prototype and not a completed diagnostic tool. The scientists developing this tool have made inroads in four primary areas: anxiety and depression, substance use problems, personality problems and psychotic disorders.

“The HiTOP system currently is incomplete, as it primarily focuses on more common and widely studied forms of psychopathology,” Watson suggested, “but mental health professionals certainly could use it to assess/ diagnose a broad range of conditions.” Mental health professionals can view this new resource at the website https://medicine.stonybrookmedicine.edu/HITOP.

Kotov hopes this new paradigm will “focus on science and do everything we can to keep unpolitical, nonscientific considerations out of it,” he said. “We hope that it provides the most up-to-date alternative” to the DSM. The HiTOP approach, Kotov said, relies more heavily on scientific evidence, which can include genetic vulnerabilities, environmental risk factors and neurobiological abnormalities.

Kotov, who is working on several projects, said HiTOP takes about a quarter of his time. He is also involved with a long-term study of schizophrenia and bipolar disorders, which was started in the early 1990s, before he arrived at Stony Brook in 2006.

Kotov is following up on this cohort, looking at outcomes for treatment and analyzing risk factors and processes that determine the course of an illness. He is also leading a study on first responders to the 9-11 attack on the World Trade Center, which is exploring the physical and emotional consequences of participating in the response to the unprecedented attack.

Kotov and his collaborators are investigating the health of responders in their daily life using mobile technology. They are also studying how personalities affect their health, which may soon help guide personalized treatment.

Another project involves the study of children who are 14 to 17 years old and explores the emotional growth and personality development. This study includes reports, surveys and interviews. During those years, “much happens as far as personality development,” Kotov said.

Colleagues at Stony Brook praised Kotov’s scientific contributions. Kotov is a “rising star” and is “perhaps best known for his work on the role of personality in psychopathology and, increasingly, for work on classification of psychiatric disorders,” Daniel Klein, a distinguished professor in the Department of Psychology at Stony Brook, wrote in an email.

A resident of Port Jefferson, Kotov lives with his wife Tatiana, who is a controller for a small company in Manhattan. The couple has two young daughters. Kotov grew up in Russia in a small town near Moscow. He was always interested in science and developed a particular curiosity about psychology when a high school psychology teacher sparked his interest when he was 15.

As for the HiTOP effort, Kotov is convinced this endeavor will offer the mental health community a valuable tool. “We believe that describing patients more accurately, precisely and reliably will help provide better and more personalized care,” he said.

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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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At the ribbon cutting of the Kavita and Lalit Bahl Center for Metabolomics and Imaging last December, from left, Lina Obeid; Yusuf Hannun; Kavita and Lalit Bahl; Samuel Stanley, President of Stony Brook University; and Kenneth Kaushansky, dean of Stony Brook University’s School of Medicine. Photo from SBU

By Daniel Dunaief

Many ways to kill cancer involve tapping into a cell’s own termination system. With several cancers, however, the treatment only works until it becomes resistant to the therapy, bringing back a life-threatening disease.

Collaborating with researchers at several other institutions, Dr. Lina Obeid, the director of research at Stony Brook University School of Medicine, has uncovered a way that cancer hides a cell-destroying lipid called ceramide from treatments. The ceramide “gets co-opted by fatty acids for a different species of fats, namely acylceramide, and gets stored side by side with the usual triglycerides,” Obeid explained in an email about her recent finding, which was published in the journal Cell Metabolism. “It makes the ceramide inaccessible and hence the novelty.” The ceramide gets stored as a lipid drop in the cell.

“We describe a completely new metabolic pathway and role in cell biology,” Obeid said. Other researchers suggested that this finding could be important in the battle against cancer. “That acylceramides are formed and deposited in lipid droplets is an amazing finding,” George Carman, the director of the Rutgers Center for Lipid Research, explained in an email. “By modifying the ceramide molecule with an acyl group for its deposit in a lipid droplet takes ceramide out of action and, thus, ineffective as an agent to cause death of cancer cells.”

Carman said Obeid, whom he has known for several years, visited his campus in New Jersey to share her results. “All of us at Rutgers were so excited to hear her story because we knew how important this discovery is to the field of lipid droplet biology as well as to cancer biology,” he said. Obeid conducted some of the work at the Kavita and Lalit Bahl Center for Metabolomics and Imaging at Stony Brook University. The center officially opened on Dec. 1 of last year on the 15th floor of the Health Sciences Center and will move to the Medical and Research Translation Building when it is completed next year. “This study is exactly the kind of major questions we are addressing in the center that [the Bahls] have generously made possible,” she explained.

Obeid discovered three proteins that are involved in this metabolic pathway: a ceramide synthesizing protein called CerS, a fatty acyl-CoA synthetase protein called ACSL and an enzyme that puts them together, called DGAT2, which is also used in fatty triglyceride synthesis. Her research team, which includes scientists from Columbia University, Northrop Veterans Affairs Medical Center and Mansoura University in Egypt is looking into implications for the role of this novel pathway as a target for cancer and obesity.

Indeed, obesity enables more frequent conversion of ceramide into acylceramide. “Fats in cells and in diets increase and predispose to obesity,” Obeid suggested. “This new pathway we found occurs when fatty acids are fed to cells or as high-fat diets are fed to mice.” In theory, this could explain why obesity may predispose people to cancer or make cancer resistance more prevalent for some people. According to Obeid, a high-fat diet can cause this collection of proteins to form in the liver of mice, and she would like to explore the same pathways in humans. Before she can begin any such studies, however, she would need numerous approvals from institutional review boards, among others.

Obeid and her collaborators hypothesize that a lower-fat diet could reduce the likelihood that this lipid would be able to evade cancer therapies.

These kinds of studies “provide the justification for looking at the effect of diet on acylceramide production,” Daniel Raben, a professor of biological chemistry at Johns Hopkins University School of Medicine, explained in an email. Further research could include “isocaloric studies with [high-fat diets] and [low-fat diets] in animals that are age and gender matched.”

Obeid was a part of the first group to describe the lipid’s role in cancer cell death in 1993. “We have been studying its metabolism and looking at how it’s made and broken down,” she said. “We found recently that it associates with these proteins to metabolize it.”

While the lipid provides a way to tackle cancer’s resistance to chemotherapy, it also has other functions in cells, including as a membrane permeability barrier and in skin. A therapy that reduced acylceramide could affect these other areas but “as with hair loss [with chemotherapy treatment], this will likely be easily managed and reversible,” Raben explained.

Obeid and Yusuf Hannun, the director of the Cancer Center at Stony Brook, are searching for other scientists to work at the Kavita and Lalit Bahl Center for Metabolomics and Imaging. “We are actively recruiting for star scientists” at the center, Obeid said. Other researchers suggested that the history of the work Obeid and Hannun have done will attract other researchers.

Hannun and Obeid are “considered the absolute leaders in the area of sphingolipid biochemistry and their clinical implications,” Raben said. “Simply put, they are at the top of this academic pile. Not only are they terrific scientists, they also have an outstanding and well-recognized reputation for training and nurturing young investigators.” Carman asked, “Who wouldn’t want to be associated with a group that continues to make seminal contributions to cancer biology and make an impact on the lives of so many?”

As for the next steps in this particular effort, Carman foresaw some ways to extend this work into the clinical arena. “I can imagine the discovery of a drug that might be used to combat cancer growth,” Carman said. “I can imagine the discovery of a drug that might control the acylation of ceramide to make ceramide more available as a cancer cell inhibitor. Clearly, [Obeid’s] group, along with the outstanding colleagues and facilities at Stony Brook, are positioned to make such discoveries.”

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Line Pouchard at the Great Smoky Mountains National Park in 2013. Photo by Allan Miller

By Daniel Dunaief

They produce so much information that they can’t keep up with it. They use the latest technology to gather data. Somewhere, hidden inside the numbers, might be the answer to current questions as well as the clues that lead to future questions researchers don’t know how to ask yet.

Scientists in almost every facility, including at Brookhaven National Laboratory, Cold Spring Harbor Laboratory and Stony Brook University, are producing information at an unprecedented rate. The Center for Data-Driven Discovery at Brookhaven National Laboratory can help interpret and make sense of all that information.

Senior researcher Line Pouchard joined BNL’s data team early this year, after a career that included 15 years at Oak Ridge National Laboratory (another Department of Energy facility) and more than two-and-a-half years at Purdue University. “The collaborations at the [DOE] lab are highly effective,” she said. “They have a common purpose and a common structure for the scientist.” Pouchard’s efforts will involve working with metadata, which adds annotations to provide context and a history of a file, and machine learning, which explores large blocks of information for patterns. “As science grows and the facility grows, we are creating more data,” she said.

Scientists can share large quantities of information, passing files through various computer systems. “You may want to know how this data has been created, what the computer applications or codes are that have been used, who developed it and who the authors are,” she said.

Knowing where the information originated can help the researchers determine whether to trust the content and the way it came together, although there are other requirements to ensure that scientists can trust the data. If the metadata and documentation are done properly “this can tell you how you can use it and what kind of applications and programs you can use to continue working with it,” Pouchard said. Working in the Computational Science Initiative, Pouchard will divide her time between responding to requests for assistance and conducting her own research.

“At Purdue, [Pouchard] was quite adept at educating others in understanding metadata, and the growing interest and emphasis on big data in particular,” explained Jean-Pierre Herubel, a professor of library science at Purdue, in an email. Herubel and Pouchard were on the research council committee, and worked together with other members to shepherd their research agendas for the Purdue University library faculty.

Pouchard “has a capacity to participate well with colleagues; regarding national and international venues, she will be a strong participating member,” Herubel continued. “She does well working and integrating with others.”

Pouchard recently joined a team that submitted a proposal in the area of earth science and data preservation. She has also worked on something called the Semantic Web. The idea, which was proposed by Tim Berners-Lee, who invented the World Wide Web, is to allow the use of data items and natural language concepts in machine readable and machine actionable forms. As an example, this could include generating rules for computers that direct the machines to handle the multiple meanings of a word.

One use of the Semantic Web is through searches, which allows people to look for information and data and, once they’re collected, gives them a chance to sort through them. Combined with other technologies, the Semantic Web can allow machines to do the equivalent of searching through enormous troves of haystacks.

“When I first started talking about the Semantic Web, I was at Oak Ridge in the early days,” Pouchard said. Since then, there has been considerable progress, and the work and effort have received more support from scientists.

Pouchard was recently asked to “work with ontologies [a Semantic Web technology] in a proposal,” she said, which suggests they are getting more traction. She is looking forward to collaborating with several scientists at BNL, including Kerstin Kleese van Dam, the director of the Computational Sciences Initiative and the interim director of the Center for Data-Driven Discovery.

Kleese van Dam has “an incredible vision of what is needed in science in order to improve computational science,” said Pouchard, who met the director about a decade ago when van Dam was working in England. Pouchard has an interest in data repositories, which she explored when she worked at Purdue University.

Living temporarily in Wading River, Pouchard bought a home in Rocky Point and hopes to move in soon. Her partner Allan Miller, from Knoxville, Tennessee, owned and managed the Disc Exchange in Knoxville for 26 years. He is starting to help small business owners and non-profit organizations with advertising needs. Pouchard experienced Long Island when she was conducting her Ph.D. research at the City University of New York and took time out to visit a friend who lived in Port Jefferson.

When she’s not working on the computer, Pouchard, who is originally from Normandy, France, enjoys scuba diving, which she has done in the Caribbean, in Hawaii, in Mexico and a host of other places.

When Pouchard was young, she visited with her grandparents during the summer at the beach in Normandy, in the town of Barneville-Carteret. Her parents, and others in the area, lectured their children never to go near or touch metal objects they found in the dunes because unexploded World War II devices were still occasionally found in remote areas. The environment on Long Island, with the marshes, reminds her of her visits years ago.

Pouchard has an M.S. in information science from the University of Tennessee and a Ph.D. in comparative literature from the City University of New York.

As for her work, Pouchard said she is “really interested in the Computational Science Initiative at BNL, which enables researchers to collaborate. Computational science is an integral part of the facilities,” at her new research home.

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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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Joseph Schwartz, right, with a collaborator, Daichi Shimbo, the director of the Translational Lab at the Center for Behavioral Cardiovascular Health at Columbia University Medical Center, in front of a poster they presented at an annual meeting of the American Society of Hypertension in New York City in 2013.Photo by John Booth, III

By Daniel Dunaief

The cardiovascular skies may be clear and sunny, but there could also be a storm lurking behind them. About one in eight people who get a normal reading for their blood pressure have what’s called masked hypertension.

That’s the finding in a recent study published in the American Journal of Epidemiology led by Joseph Schwartz, a professor of psychiatry and sociology at Stony Brook University and a lecturer of medicine at the Columbia University Medical Center. Schwartz said his research suggests that some people may need closer monitoring to pick up the kinds of warning signs that might lead to serious conditions.

“The literature clearly shows that those with masked hypertension are more likely to have subclinical disease and are at an increased risk of a future heart attack or stroke,” Schwartz explained in an email.

Tyla Yurgel, Schwartz’s lab manager from 2005 to 2016 who is now working in the Department of Psychiatry, wears the ambulatory blood pressure cuff that was a part of the study. Photo by Arthur Stone

Schwartz and his colleagues measured ambulatory blood pressure, in which test subjects wore a device that records blood pressure about every half hour, collecting a set of readings as a person goes about the ordinary tasks involved in his or her life. Through this reading, he was able, with some statistical monitoring, to determine that about 17 million Americans have masked hypertension, a term he coined in 2002.

Schwartz, who started studying ambulatory blood pressure in the late 1980s, has been actively exploring masked hypertension for over a decade. Ambulatory blood pressure monitoring is more effective at predicting subclinical disease such as left ventricular hypertrophy and the risk of future cardiovascular events, said Schwartz. “There was some rapidly growing evidence it was a better predictor of who would have a heart attack or stroke than in the clinic, even when the blood pressure in the clinic was properly measured,” he said.

To be sure, the expense of 24-hour monitoring of ambulatory blood pressure for everyone is unwieldy and unrealistic, Schwartz said. The list price for having an ambulatory blood pressure recording is $200 to $400, he said. Wearing the device is also a nuisance, which most people wouldn’t accept unless it was likely to be clinically useful or, as he suggested, they were paid as a research participant.

Schwartz said he used a model similar to one an economist might employ. Economists, he said, develop simulation models all the time. He said over 900 people visited the clinic three times as a part of the study. The researchers took three blood pressure readings at each visit. The average of those readings was more reliable than a single reading.

The study participants then provided 30 to 40 blood pressure readings in a day and averaged those numbers. He collected separate data for periods when people were awake or asleep. A patient close to the line for hypertension in the clinical setting was the most likely to cross the boundaries that define hypertension. “You don’t have that far to go to cross that boundary,” Schwartz said.

After analyzing the information, he came up with a rate of about 12.3 percent for masked hypertension of those with a normal clinic blood pressure. The rate was even higher, at 15.7 percent, when the researchers used an average of the nine readings taken during the patient’s first three study visits.

William White, a professor of medicine at the Calhoun Cardiology Center at the University of Connecticut School of Medicine in Farmington was a reviewer for one of these major studies. “They are excellent,” said White, who has known Schwartz for about a decade. “We should be monitoring blood pressure more outside of the clinical environment.”

Indeed, patients have become increasingly interested in checking their blood pressure outside of the doctor’s offices. “We have a 200 to 300 percent increase in requests for ambulatory blood pressure monitoring from our clinical lab during the last five to ten years — in all age groups, genders and ethnicities,” explained White.

The challenge, however, is that tracking hypertension closely for every possible patient is difficult clinically and financially. “There are no obvious clinical markers for masked hypertension other than unexpectedly high self-blood pressure or unexplained hypertensive target organ damage,” White added.

Schwartz himself has a family history that includes cardiovascular challenges. His father, Richard Schwartz, who conducted nonmedical research, has a long history of cardiovascular disease and had a heart attack at the age of 53. His grandfather had a fatal heart attack at the same age. When Schwartz reached 53, he said he had “second thoughts,” and wanted to get through that year without having a heart attack. He’s monitoring his own health carefully and is the first one in his family to take blood pressure medication.

Schwartz, who grew up in Ithaca, New York, came to Stony Brook University in 1987. He called his upbringing a “nonstressful place to grow up.” He now lives in East Setauket with his wife Madeline Taylor, who is a retired school teacher from the Middle Country school district. The couple has two children. Lia lives in Westchester and works at Graham Windham School and Jeremy lives in Chelsea and works for Credit Suisse.

As for his work, Schwartz said the current study on masked hypertension was a part of a broader effort to categorize and understand pre-clinical indications of heart problems and to track the development of hypertension.

Now that he has an estimate of how many people might have masked hypertension, he plans to explore the data further. That analysis will examine whether having masked hypertension puts a patient at risk of having cardiovascular disease or other circulatory challenges. “We are very interested in whether certain personality characteristics and/or circumstances (stressful work situation) makes it more likely that one will have masked hypertension,” he explained.

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Benjamin Martin in his lab at Stony Brook University. Photo courtesy of SBU

By Daniel Dunaief

Last week, the Times Beacon Record Newspapers profiled the work of David Matus, an assistant professor in the Department of Biochemistry and Cell Biology. Matus and Benjamin Martin, who has the same title in the same department, are working together on a new cancer study.

While neither Matus nor Martin are cancer biologists, these researchers have experience in developmental biology with different organisms that could contribute to insights in cancer. Specifically, they are exploring the processes that lead to cell division or invasion. Matus is working with the transparent roundworm, while Martin is focusing on the zebrafish.

The duo recently won the 2017 Damon Runyon–Rachleff Innovation Award, which includes a grant of $300,000. Martin got involved in the research “based on learning more about [Matus’] work and the general hypothesis” about division and invasion, Martin said. The overall perspective is that the cell doesn’t “invade through tissues and divide at the same time.”

Martin has done innovative work with a neuromesodermal progenitor in the zebrafish. These cells are highly plastic and can give rise to numerous other cell types. Martin is focused on trying to understand the basic biology of these cells.

From left, David Matus and Benjamin Martin in the lab where they investigate metastatic cancer. Photo courtesy of SBU

Martin is known for the “very original discovery that a signaling protein called Wnt can regulate the decision between these progenitor cells becoming muscle or neurons,” explained David Kimelman, a professor of Biochemistry at the University of Washington who oversaw Martin’s research when he was a postdoctoral student.

“What is very nice is that [Martin’s] discovery in zebrafish has since been replicated in other organisms such as the mouse and even in human stem cells, showing that this is a fundamental property of vertebrates,” Kimelman explained in an email.

Similar to Matus’ work with the worm, Martin has been working with cells that go through invasive behavior and don’t engage in cell proliferative activities. “We already knew that notochord progenitors are not proliferating when they undergo convergence and extension” from other published works, explained Martin in an email. “Since notochord progenitors exist in the tailbud and we were already studying them, it was a natural jumping off point to address the same question.”

Martin is testing a transcription factor, called brachyury, which drives metasasis-like behavior in human cancer cells. He has studied this transcription factor in the context of early zebrafish development and will see if it helps drive metastasis through inhibition of the cell cycle. At this point, Martin said, there is some “evidence that it does arrest the cell cycle” using human cells in another lab.

So far, the work he has done with brachyury and the cell cycle/invasion in zebrafish is preliminary. Their hypothesis is that halting the cell cycle is a prerequisite for invasive behavior. Like the roundworm, the embryonic zebrafish is transparent, which makes it easier to observe cellular changes.

One of the goals of the project is “to observe the cell cycle of human cancer as it invades through tissues in the fish embryo,” Martin said. In the long term, he hopes to see whether the overexpression of a transcription factor Matus has found in the worm is sufficient to drive metastasis in the zebrafish.

Martin described winning the Damon Runyon–Rachleff Award as “exciting,” and suggested that it “pushes back a little bit of the worry phase” of finding funding for compelling scientific projects. Kimelman said Martin is an “exceptional scientist” and one of the “best I have had the privilege to train.”

Kimelman believes the work Martin and Matus are doing has the potential to provide “important insight into the basic changes that occur during cancer as cells become metastatic,” he explained in an email. “While it doesn’t immediately lead to a therapeutic, understanding the basic biology of cancer is the first step to defining new ways of affecting it.”

Kimelman particularly appreciated the way Matus and Martin combined two different model systems, which offers the potential to provide insight into the basic changes that occur during cancer as cells become metastatic.

Martin learned about science and research during his formative years. His father Presley Martin was a graduate student at Johns Hopkins in Baltimore when the younger Martin was born. Presley Martin recently retired from Hamline University in St. Paul, Minnesota, where he studied the genetics of the fruit fly Drosophila. “At a young age, I was exposed to a lot of the lab and experiments and it was certainly appealing to me,” said Martin.

Benjamin Martin with his son Calvin. Photo by Richard Row

Martin is married to Jin Bae, whom he met at the University of California at Berkeley, where he was studying the molecular control of how muscle precursor cells move to distant parts of the embryo in frogs and fish. Bae is a registered nurse at Stony Brook Hospital. The couple’s son Calvin, who enjoys visiting the lab, will be four in April.

Matus and Martin are collaborating with Scott Powers, a professor in the Department of Pathology at Stony Brook, and Eric Brouzes, an assistant professor in the Department of Biomedical Engineering at Stony Brook.

Powers said the work Martin and Matus are doing is a “basic discovery but an important one,” he explained in an email. “Conceivably, further research could lead to translation but as of right now, any thoughts along those lines are speculative.”

Martin appreciates the opportunity to work on these cells that are so important in development and that might lead to insights about cancer. “It seems like in the past few years” these discoveries have “opened up a subfield of developmental biology,” he said. “It’s exciting to see.”

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David Matus in his lab at Stony Brook University. Photo courtesy of SBU

By Daniel Dunaief

At first look, the connection between a roundworm, a zebrafish and cancer appears distant. After all, what can a transparent worm or a tropical fish native to India and the surrounding areas reveal about a disease that ravages its victims and devastates their families each year?

Plenty, when talking to David Matus and Benjamin Martin, assistant professors in the Department of Biochemistry and Cell Biology at Stony Brook University whose labs are next door to each other. The scientific tandem recently received the 2017 Damon Runyon–Rachleff Innovation Award, which includes a two-year grant of $300,000, followed by another renewable grant of $300,000 to continue this work.

In the first of a two-part series, Times Beacon Record Newspapers will profile the work of Matus this week. Next week the Power of Three will feature Martin’s research on zebrafish.

Long ago a scientist studying dolphin cognition in Hawaii, Matus has since delved into the world of genetic development, studying the roundworm, or, as its known by its scientific name, Caenorhabditis elegans. An adult of this worm, which lives in temperate soil environments, measures about 1 millimeter, which means it would take about 70 of them lined up end to end to equal the length of an average earthworm.

From left, David Matus and Benjamin Martin. Photo courtesy of SBU

Matus specifically is interested in exploring how a cell called the anchor cell in a roundworm invades through the basement membrane, initiating a uterine-vulval connection that allows adult roundworms to pass eggs to the outside environment. He is searching for the signals and genetic changes that give the anchor cell its invasive properties.

Indeed, it was through a serendipitous discovery that he observed that the loss of a single gene results in anchor cells that divide but don’t invade. These dividing cells are still anchor cells, but they have lost the capacity to breach the basement membrane. That, Matus said, has led the team to explore the ways cancer has to decide whether to become metastatic and invade other cells or proliferate, producing more copies of itself. In some cancers, their hypothesis suggests, the cells either divide or invade and can’t do both at the same time. It could be a cancer multitasking bottleneck.

Mark Martindale, the director of the Whitney Laboratory at the University of Florida in Gainesville who was Matus’ doctoral advisor, said a cell’s decision about when to attach to other cells and when to let go involves cell polarity, the energetics of motility and a host of other factors that are impossible to study in a mammal.

The roundworm presents a system “in which it is possible to manipulate gene expression, and their clear optical properties make them ideal for imaging living cell behavior,” Martindale explained in an email. Seeing these developmental steps allows one to “understand a variety of biomedical issues.”

Last year, Matus and Martin were finalists for the Runyon–Rachleff prize. In between almost getting the award and this year, the team conducted imaging experiments in collaboration with Eric Betzig, a group leader at the Janelia Research Campus of the Howard Hughes Medical Institute in Ashburn, Virginia. Betzig not only brings expertise in optical imaging technologies but also has won a Nobel Prize.

“We really appreciate the opportunity to work with [Betzig] and his lab members on this project,” said Matus, who also published a review paper in Trends in Cell Biology that explored the link between cell cycle regulation and invasion. He and his graduate student Abraham Kohrman explored the literature to find cases that showed the same switching that he has been exploring with the roundworm.

Yusuf Hannun, the director of the Stony Brook Cancer Center, said the work is highly relevant to cancer as it explores fundamental issues about how cells behave when they invade, which is a key property of cancer cells. Hannun said the tandem’s hypothesis about division and invasion is “consistent with previous understandings but I believe this is the first time it is proposed formally,” he suggested in an email.

Their work could apply to invasive epithelial cancers, suggested Scott Powers, a professor in the Department of Pathology at Stony Brook and the director of Clinical Cancer Genomics at the Cancer Center. That could include breast, colon, prostate, lung and pancreatic cancers, noted Powers, who is a recent collaborator with Matus and Martin.

The additional funding allows Matus and Martin to focus more of their time on their research and less on applying for other grants, Matus said.

Back row from left, David Matus and his father in law Doug Killebrew; front row from left, Maile 9, Bria, 7, and Matus’ wife Deirdre Killebrew. Photo by Richard Row

Matus lives in East Setauket with his wife Deirdre Killebrew, who works for Applied DNA Sciences. The couple met when they were working with dolphins in Hawaii. Matus’ first paper was on dolphin cognition, although he switched to evolutionary and developmental biology when he worked in Martindale’s lab at the University of Hawaii.

Martindale described Matus as prolific during his time in his lab, publishing numerous papers that were “profoundly important in our continued understanding of the relationship between genotype and phenotype and the evolution of biological complexity,” Martindale wrote in an email.

Following in Martindale’s footsteps, Matus replaced his middle name, Samuel, in publications with a Q. Martindale said several of his colleagues adopted the phony Q to pay homage to the attitude that drove them to pursue careers in science. Matus has now passed that Q on to Korhman, who is his first graduate student.

Matus and Killibrew have two daughters, Bria and Maille, who are 7 and 9 years old. Their children have a last name that combines each of their surnames, Matubrew. Matus said he feels “fortunate when I got here three years ago that they had me set up my lab next to [Martin]. That gave us an instantaneous atmosphere for collaboration.”

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By Daniel Dunaief

 

Adrian Krainer with Emma Larson earlier this year. Photo from Dianne Larson

The prognosis hit Dianne Larson of Middle Island hard. Within three weeks, anxiety attacks, a lack of sleep and fear caused her weight to plummet from 135 to 120 pounds. She found out her daughter Emma, who was 17 months old at the time, had a potentially fatal genetic condition called spinal muscular atrophy in which the motor nerve cells of the spinal cord progressively weaken. Normally, the SMN1 gene produces the survival of motor neuron protein, which, as its name suggests, helps maintain motor neurons. People with SMA, which has four types and severity, produce a lower amount of the functional protein.

“My mind went to the darkest of dark places,” said Larson, whose daughter couldn’t crawl or sit up to eat. “There was no hope. There was nothing I could do.”

At the time of Emma’s diagnosis, there was no treatment for a disease that is the leading genetic cause of death among infants and affects about 1 in 10,000 newborns. Thanks to the work of Adrian Krainer, a professor and program chair of cancer and molecular biology at Cold Spring Harbor Laboratory, that changed early enough to alter the expectations for Emma and children around the world battling a genetic condition that causes progressive weakness and can make moving and even breathing difficult.

Turning to a back up gene called SMN2, Krainer hoped to fix a problem with the way that gene is spliced. On SMN2, exon 7 is normally skipped and the resulting protein has a different sequence at the end. Krainer developed an antisense olignocleotide that binds to a sequence in the intro following exon 7, blocking the splicing receptor. The treatment, which is called Spinraza, helps guide the splicing machinery, which carries out one of the steps in gene expression that is necessary to build a functional protein.

The Larson family of Middle Island, from left, Dianne, Emma and Matthew. Photo from Dianne Larson

Larson had heard of Krainer’s work and was eager to see if his success with animal models of the disease would translate for humans. As soon as Emma reached her second birthday, Larson enrolled her daughter in a clinical trial for Spinraza. After her daughter had a few shots, Larson was stunned by the change. “I was in the master bedroom and she was in the den and I heard a voice getting closer,” Larson recalls. “Next thing I know, she was in my bedroom. I couldn’t believe she crawled from the den to the bedroom. I put her in the den and told her to do it again,” which she did.

The SMA community and Krainer received an early holiday present in late December when the Food and Drug Administration not only approved the treatment, but it also gave doctors the green light to prescribe it for all types of SMA and for patients of all ages. While the SMA community, doctors and Krainer have been delighted with the FDA approval, the excitement has been tempered by concerns about the price tag Biogen, which manufactures and commercializes Spinraza and funded the drug’s development, has placed on the treatment.

For the first full year of injections, the drug costs $750,000. Every year after that will cost $375,000, which Biogen has said publicly is consistent with the pricing for other drugs for so-called orphan diseases, which affect a much smaller percentage of the population.

Knowledge Ecology International, a nonprofit advocate for affordable medicines, sent a letter to the Office of the Inspector General at the Department of Health and Human Services, seeking an investigation. The letter claims that the inventor and maker of Spinraza failed to disclose that the treatment received federal funding. KEI urges the government to use that alleged disclosure failure to end the patent and authorize a generic manufacture of the treatment.

Biogen didn’t return a call and email for comment. Patients and their families, meanwhile, are looking for immediate access to a life-altering treatment. “To be honest, I really don’t know what we’re going to do,” said Larson, whose daughter has four injections left as part of the extension trial soon. “I’m hoping insurance will cover it.”

Insurer Anthem announced late in January that the treatment was only medically necessary for patients with Type 1 SMA, which include people diagnosed with the disease within six months of birth. Anthem created a pay for performance model, which will require patients or their families to prove that the treatment is improving the lives of the recipients.

Larson said she has been in touch with a personal liaison at Biogen, which has been “helpful and supportive,” she said. “They have been going out of their way to reach out to the community to make sure everyone gets access.”

Larson, who is a financial advisor, said she understands the need for the company to generate a profit. “A lot of money goes into” research and development Larson said. “If they’re not gong to make money, they’re not going to” support the efforts to create a treatment.

Emma Larson will be turning 4 this month. Photo from Dianne Larson

Joe Slay, who is the chairman of FightSMA, a group he and his wife Martha founded in 1991 after they learned their son Andrew had Type 2 SMA, sounded hopeful that people who need this treatment will receive it. “I understand there’s constructive, good conversations between insurance companies and Biogen,” Slay said. “We’re monitoring that.”

While Andrew, who is now 30, considers the potential benefits of Spinraza, Slay is pleased the treatment is an option for people and is proud of Krainer’s work.Krainer is “by any definition of the word a hero,” Slay said. “He’s taken his natural gifts, his brilliance in science, his discipline year in and year out approach to his work and has applied himself 100 percent.”

Slay and FightSMA, which has raised over $8 million since its founding, helped provide seed money to Krainer more than 15 years ago, attracting a promising scientist to what was then an intractable medical challenge.

Tom Maniatis, who is the chairman of the Department of Biochemistry and Molecular Biophysics at Columbia University, said Krainer, who did his doctoral work in Maniatis’s lab, showed considerable scientific promise early in his career. Krainer “clearly had the intelligence, drive and experimental skills to make important contributions,” Maniatis said. His work is “a perfect example of how deep basic science studies can lead to profound understanding of a disease mechanism and that, in turn to the development of a treatment,” explained Maniatis in an email.

Within Krainer’s own family, there is a connection to patient care. Krainer’s daughter Emily, who is a pediatric neurology resident at Rochester, may one day prescribe a treatment her father developed. “It will be quite something for me if she eventually prescribes Spinraza to one of her patients,” Krainer said. Even as other scientists and companies like AveXis continue to search for ways to treat SMA, Krainer enhances and refines his research.

“We continue to work on understanding aspects of SMA pathophysiology, the role of SMN levels outside the central nervous system and the potential for prenatal therapy,” he explained in an email. “We are also working on antisense therapies for other genetic diseases and cancer.”

Larson, who is overjoyed with her daughter’s progress, calls Krainer her “superhero” who “saved my daughter’s life.” “It’s such a different feeling when you know you can do something,” she said. When she found out that the FDA approved the treatment, it was “the best day.”

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Liliana Davalos, right in blue and white shirt, in La Victoria, Colombia with the paleo team from Grand Valley State University during a fossil dig last year. Photo courtesy of Siobhán Cooke

By Daniel Dunaief 

It’s like that old bus riddle. The bus starts out with 20 people. Six people get off, then eight get on, two more get off, 12 enter, eight exit, and so on until, lo and behold, the bus has either the same number of people or someone asks the identity of the driver.

In this case, though, the bus is a collection of Caribbean islands called the Greater Antilles, which includes the Dominican Republic, Cuba, Hispaniola, Haiti, Puerto Rico, the Cayman Islands and Jamaica. The passengers are not people; they are species of bats.

Working with Luis Valente, a postdoctoral researcher at the Natural History Museum of Berlin, Liliana Davalos, an associate professor of conservation biology/ecology and evolution at Stony Brook University, recently determined that the number of species of bats, like the people entering and leaving the bus, remained in relative equilibrium for millions of years over many generations.

Liliana Davalos at La Venta site in Colombia with a rainbow in the background.Photo courtesy of Siobhán Cooke

While several species of bats will colonize the islands and new species will also form over that long time scale, the rate of natural extinction in that time balances out the islands’ diversity gains, leaving the metaphorical bus with about the same number of species.

Famous biologists Edward O. Wilson and Robert MacArthur came up with the theory of island biogeography in 1967, which might help explain how the number of species of bats remained in equilibrium for millions of years. The theory proposes an equilibrium between colonization and extinction.

For bats, however, that balance changed. About 20,000 years ago, fossils of extinct species made their final appearance, while other species died off about 3,000 to 4,000 years ago. So, what happened to the bat bus?

The last ice age accounts for some of the declines about 20,000 years ago. More recently, the arrival of people altered conditions on the islands. At least two other waves of colonization occurred before the arrival of Europeans, with people changing the landscape through agriculture. While hunting of other mammals is evident from the archeological record, it is less certain how changes on the land affected bats. It’s difficult to pinpoint the exact time when each species went extinct, although many of those events happened after people arrived on the islands, changing the region’s equilibrium.

Davalos’ previous work had found that the number of species lost was as predicted if the losses occurred because of the rising sea levels at the end of the last glaciation. If that were the case, many of those species would have disappeared around that time. Some of her colleagues, however, dated the remains of bats and found that these species became extinct more recently, over the last few thousand years.

“While we cannot be certain that all bat extinctions were caused by humans, evidence increasingly seems to suggest so,” explained Valente in an email. “All over the world, colonization of islands by humans has led to many extinctions of local species, because islands have very unique species that are very prone to any disturbances.”

The researchers used computer simulations to calculate that it would take nature eight million years to restore bat biodiversity. “Some people argue that if we leave nature alone it will quickly return to its original state,” Valente explained. “However, the finding that it would take eight million years to recover lost diversity suggests that is clearly not the case.” Valente, who described Davalos as a “wonderful collaborator” who was “actively involved in the project at all stages,” wrote that this study “raises awareness for conservation of the unique bat species of the Caribbean.”

While there is still work ahead, the “nations of the Greater Antilles have amazing natural parks to protect their biodiversity,” Davalos explained. In the tropics of the Western Hemisphere, Puerto Rico is the “number one example of a forest growing back,” Davalos said. “Puerto Rico is one of the places in the world that has had more of a resurgence of the forest.”

The preservation of biodiversity remains threatened even now as at least three bat populations on the Greater Antilles are threatened with extinction and two might already be extinct. Still, the effort is not “hopeless,” she said, as there are some large populations of bats thriving on these islands. Davalos and her colleagues were able to make these discoveries by examining the bat in detail.

A resident of Setauket, Davalos has been at Stony Brook University for eight years. She enjoys kayaking on Long Island and visiting local and state parks. Over the last few years, she has spent her free time on staycations, where she sees a protected area of Long Island each day.

From a young age, Davalos recalls being interested in science. Indeed, when she was only 4, she saw a documentary where Louis and Mary Leakey showed the results of their expeditions where they collected human fossils in Kenya. “From that moment on,” Davalos recalled, “I thought, ‘Some day, this is what I’m going to study.’” Her family and their acquaintances suggested that pursuing such a career path would be challenging.

She tells her current SBU students that she’s “the luckiest person in the world, living out my childhood dream.” Last year, she went on her first fossil dig in Colombia, where she joined a team from Grand Valley State University in Allendale, Michigan, and Johns Hopkins. She found fossils from bats that were 12 million years old.

While Davalos has never met the Leakey family, she wants to tell them that, “Children are watching and [their work] can have a huge effect” on their dreams. Some day, Davalos hopes a future scientist may say the same thing about her research.

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