DAVID TANK receives Brain Prize for advance in microscopy

PHOTO BY WINFRIED DENK

PHOTO BY WINFRIED DENK

David Tank, the Henry L. Hillman Professor in Molecular Biology and co-director of the Princeton Neuroscience Institute, has been named one of four winners of the Brain Prize, an honor that recognizes scientists who have made outstanding contributions to brain research.

Tank was presented the prize by His Royal Highness Crown Prince Frederik of Denmark on May 7, 2015, in Copenhagen. He shares the 1 million euro, or roughly $1,085,000, prize with Winfried Denk of the Max Planck Institute of Neurobiology in Munich; Arthur Konnerth of the Technical University of Munich; and Karel Svoboda of the Howard Hughes Medical Institute in Chevy Chase, Maryland.

The researchers were selected for the invention, development and application of two-photon microscopy, a technology that combines advanced techniques from physics and biology to allow scientists to examine the finest structures of the brain in real time.

“Thanks to these four scientists we’re now able to study the normal brain’s development and attempt to understand what goes wrong when we’re affected by destructive diseases such as Alzheimer’s and other types of dementia,” said Professor Povl Krogsgaard- Larsen, chair of the Grete Lundbeck European Brain Research Foundation, which awards the prize.

–By Michael Hotchkiss

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Engineering health solutions for all

Benjamin Tien

Benjamin Tien. PHOTO BY PETER LAMBERT

Hundreds of women die every day due to excessive bleeding after childbirth, but this can be prevented by an injection of the hormone oxytocin, which stimulates uterine contractions that reduce bleeding. Yet oxytocin must be kept cold, and developing countries often lack the resources to transport and store the hormone. Nor do they have enough trained personnel to administer the shot.

Benjamin Tien, who graduated from Princeton in 2015 with a degree in chemical and biological engineering, has been awarded a Fulbright grant to join a research team developing an aerosolized, inhalable version of oxytocin. He’ll work at the Monash Institute of Pharmaceutical Sciences in Australia to use a technique called “spray-drying” to turn liquid oxytocin into a dry powder that can be released from an inexpensive, disposable device. This would cut out the need for special storage conditions, eliminate the risk of infection from needles, and make the treatment available even to women giving birth at home.

While at Princeton, Tien conducted senior thesis research on nanoparticles for dealing with bacterial infections such as cholera or pseudomonas with Robert Prud’homme, a professor of chemical and biological engineering and Tien’s thesis adviser. During the summer before his senior year, Tien worked at a startup company in Boston called Diagnostics for All that develops medical diagnostics for developing countries.

While doing research in Australia, Tien will also work with the Poche Center for Indigenous Health, an organization that aims to improve the health of indigenous Australians with an emphasis on forming lasting relationships with the communities. “I want to get a better sense of the challenges people are facing on the ground, which will help me know what to focus on in my career,” Tien said.

-By Takim Williams

Tiny delivery capsules for new drugs

‘Jack’ Hoang Lu researches nanoparticles for drug delivery

Graduate student ‘Jack’ Hoang Lu works on engineering nanoparticles for targeted drug delivery and diagnostics in the laboratory of Robert Prud’homme, professor of chemical and biological engineering. PHOTO BY CATHERINE ZANDONELLA

Some drugs cannot be delivered via a normal pill or injection because they cannot readily dissolve in water. About 40 percent of new pharmaceuticals have this hydrophobic (water-fearing) character, and like a globule of oil in water, they are unable to reach their targets in the body.

Robert Prud’homme, professor of chemical and biological engineering, addresses this problem by putting the drugs inside of nanoparticles, each about one-thousandth of the width of a human hair, which are then covered with a polymer called polyethylene glycol. The small size enables dissolution of the drug to increase their bioavailability.

Nanoparticles can also tackle a different delivery challenge presented by a growing class of drugs called biologics that, as the name implies, are made from cellular or genetic components. The problem is that they are all water-soluble, which make them easy prey for patrolling proteins that identify them as foreign and degrade them. The solution is similar: nanoparticles protect the biologics long enough for them to carry out their mission.

In addition to increasing the time that drugs spend flowing through the body, Prud’homme’s nanoparticles are capable of targeted delivery. This is necessary in the case of toxic drugs, including many cancer treatments, which would damage healthy cells if allowed to roam freely throughout the body. Prud’homme puts appendages, called ligands, on the outside of his nanoparticles that, due to their specific shape and chemical properties, attach to their target and only to their target. In collaboration with Patrick Sinko at Rutgers University, Prud’homme’s group discovered the optimum density of an appendage called a mannose ligand, used to target cells harboring tuberculosis microbes. The unexpected result was that attaching more appendages to a nanoparticle decreased its targeting effectiveness. This demonstration of the complex interplay between engineered nanoparticles and how the human body responds to them is a major theme of the Prud’homme research team. In addition to tuberculosis, the researchers are using these principles to attack cancer, inflammation, and bacterial infections.

The project receives funding from the National Institutes of Health, the National Science Foundation, Princeton’s IP Accelerator Fund and the School of Engineering and Applied Sciences Old Guard Grant.

–By Takim Williams

Computer chip for point-of-care diagnosis

Lab on a chip is smaller than a penny.

Kaushik Sengupta and his team are developing a computer chip-based diagnostic system, which is smaller than a penny but contains hundreds of different sensors for simultaneous detection of disease-causing agents.

Assistant Professor of Electrical Engineering Kaushik Sengupta and his team are developing a computer chip-based diagnostic system, which rests comfortably on a fingertip but contains hundreds of different sensors for simultaneous detection of disease-causing agents. The eventual goal is to use the chip in a handheld, portable diagnostic device that could be deployed in health clinics around the globe, especially in resource-limited settings.

The chip detects and measures the presence of DNA or proteins to help diagnose health conditions. Most existing methods for detecting these agents involve shining light on fluorescent labels attached to the DNA or protein and reading a resulting signal. However, in many types of tests, the signal is so weak that complex optical equipment is necessary to read the signal.

To perform this analysis using a simple handheld device, Sengupta is co-opting silicon chip technology similar to that found in personal computers and mobile phones. “This is a great technology for handheld medical diagnostic devices because it allows us integrate extremely complex systems in a single chip at very low cost. The vision is to unleash Moore’s law in diagnostics,” said Sengupta, referring to Intel co-founder Gordon Moore’s observation that processing power in computer chips has increased rapidly over the years.

The team starts with highly sensitive light-detecting components, or photodetectors, that are already ubiquitous in smartphone cameras, then adds new optical processor capabilities to the chip. The researchers found a way to re-wire the architecture of the chip so that in addition to carrying electrical information necessary for image processing, the chip also interacts with the incoming photons from the fluorescent light, and can block them out, allowing the signal that carries information about the test sample to be detected and processed.

Lingyu Hong and Kaushik Sengupta

Lingyu Hong, a graduate student in electrical engineering, and Kaushik Sengupta, an assistant professor of electrical engineering at Princeton University are developing technology for use in a handheld diagnostic system for healthcare in resource-limited settings.

This ability to integrate optical elements with electronics inside a single silicon chip is enabling the team to build detection systems for both genetic material and proteins. Millions of photodetectors can already be crammed into smartphone cameras and Sengupta plans to put hundreds or even thousands of such sensors on the new chip to create a platform capable of testing many agents at once. In addition to being cheap and robust, this “lab-on-a-chip” will be user-friendly. Sengupta and his colleagues envision that the chips will be used in a portable device similar to a smartphone that can use an app to analyze the fluorescence data and display diagnosis results in a clear, simple format.

To make the device truly portable, it will be necessary to develop a small and lightweight apparatus to isolate proteins and genetic material from blood or other fluids, and Sengupta and his collaborators are working on this challenge. “The entire end-to-end system may take another couple of years to reach, but we’ve demonstrated the feasibility of the approach,” said Sengupta, who collaborates with Professor of Chemistry Haw Yang. “Princeton provides the kind of environment that makes it easy to reach out to faculty members across the campus and to work on creative endeavors that cut across traditional disciplines.”

The initial work on the chip was supported by Project X, a fund established through a donation from G. Lynn Shostack S’69 for the support of exploratory research. The project involvesgraduate students Lingyu Hong in the Department of Electrical Engineering and Hao Li in the Department of Chemistry, Postdoctoral Research Associate Simon McManus and undergraduate Victor Ying. Lingyu and Hao were awarded a Qualcomm Innovation Fellowship for 2015-16 for this work.

-By Takim Williams

Listening in on bacterial communications

Leah Bushin and Mohammad Syedsayamdost

While an undergraduate, Leah Bushin (left) co-authored an article on the structure of a signaling molecule involved in bacterial communication with co-first author Kelsey Schramma and adviser Mohammad Seyedsayamdost (right), assistant professor of chemistry, PHOTO BY C. TODD REICHART

BACTERIA SPEAK TO ONE ANOTHER using a soundless language known as quorum sensing. In a step toward translating bacterial communications, researchers have revealed the structure and biosynthesis of streptide, a signaling molecule involved in the quorum sensing system common to many diseasecausing streptococci bacteria.

The research team included undergraduate Leah Bushin, who was the co-first author on an article published on April 20, 2015, in Nature Chemistry. Bushin helped determine the structure of streptide as part of her undergraduate senior thesis project.

To explore how bacteria communicate, first she had to grow them, a challenging process in which oxygen had to be rigorously excluded. Next, she isolated the streptide and analyzed it using two-dimensional nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to deduce the connections between atoms.

The experiments revealed that streptide contains an unprecedented crosslink between two unactivated carbons on the amino acids lysine and tryptophan. To figure out how this novel bond was being formed, the researchers took a closer look at the gene cluster that produces streptide. Within the gene cluster, they suspected that a radical S-adenosyl methionine (SAM) enzyme, which they dubbed StrB, could be responsible for this unusual modification.

“Radical SAM enzymes catalyze absolutely amazing chemistries,” said Kelsey Schramma, a graduate student and the other co-first author on the article. The team showed that one of the iron-sulfur clusters reductively activated one molecule of SAM, kicking off a chain of one-electron (radical) reactions that gave rise to the novel carbon-carbon bond.

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

“The synergy between Leah and Kelsey was great,” said Mohammad Seyedsayamdost, an assistant professor of chemistry who led the research, which was supported by the National Institutes of Health. “They expressed interest in complementary aspects of the project, and the whole ended up being greater than the sum of its parts,” he said.

Future work will target streptide’s biological function — its meaning in the bacterial language — as well as confirming its production by other streptococcal bacteria strains.

–By Tien Nguyen

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Measles may weaken immune system up to three years

Measles vaccination

Measles may weaken immune system up to three years. PHOTO BY SHUTTERSTOCK

THE MEASLES VIRUS can lead to serious disease in children by suppressing their immune systems for up to three years, according to a study published in the journal Science on May 8, 2015. The study provides evidence that measles may throw the body into a much longer-term state of “immune amnesia,” where essential memory cells that protect the body against infectious diseases are partially wiped out. This vulnerability was previously thought to last a month or two.

“We already knew that measles attacks immune memory, and that it was immunosuppressive for a short amount of time. But this paper suggests that immune suppression lasts much longer than previously suspected,” said C. Jessica Metcalf, co-author and assistant professor of ecology and evolutionary biology and public affairs, who is affiliated with Princeton’s Woodrow Wilson School of Public and International Affairs.

The research findings suggest that — apart from the major direct benefits — measles vaccination may also provide indirect immunological protection against other infectious diseases.

The work was funded by the Bill & Melinda Gates Foundation, the Science and Technology Directorate of the Department of Homeland Security, and the Research and Policy for Infectious Disease Dynamics (RAPIDD) Program of the National Institutes of Health’s Fogarty International Center.

–By B. Rose Huber

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Princeton-Fung Global Forum focuses on global health

IN NOVEMBER, the annual Princeton-Fung Global Forum brought health experts together in Dublin to address the emergence of new diseases and challenges in an increasingly connected world. Case studies of “modern plagues,” including the Ebola crisis, framed the conversation among speakers, panelists and attendees from academia, government and nongovernmental sectors, the media, and the public. Among the conclusions: confronting the emergence of new diseases requires a multidisciplinary approach involving not only public health and medical knowledge but also an understanding of a disease’s economic, environmental, political and historical roots.

The Princeton-Fung Global Forum is a series of meetings that Princeton hosts with the help of a generous gift from 1970 alumnus William Fung.

–By Elisabeth Donahue

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Bioengineering: Unlocking the secrets of human health

Bioengineering cover imageBy Takim Williams

RED-HOT RIVERS OF MOLTEN COPPER and aluminum alloys streamed from one receptacle to another. As an undergraduate watching the demonstration in a materials science class, Clifford Brangwynne was reminded of cells migrating through the bloodstream. He realized at that moment that he could mold his interest in materials science and engineering into work that might ultimately have implications for human health.

Bioengineering blood vessel imageScientists like Brangwynne, now an assistant professor of chemical and biological engineering at Princeton, recognize the natural connection between engineering and the life sciences. Their research is setting the groundwork for future applications in health and medicine, including curing diseases such as Alzheimer’s, growing replacement organs and preventing developmental abnormalities. Each of these pursuits hinges on the understanding that living matter obeys the same principles as nonliving matter.

Discovering the relevant principles — and using them to manipulate biological systems to meet our needs — is the goal of the growing field of bioengineering. “The thing that we do that’s different from other scientists who are looking at states of matter and their properties is that we are doing it in the context of living cells,” Brangwynne said. “What is the state of matter inside of a cell and how does that enable biological function?”

Brangwynne gestures toward a can of Gillette shaving foam next to a cylinder of silly putty on his desk and explains that the familiar grade school schema of three states of matter — solid, liquid, gas — is not entirely accurate. There are phases in between, and combinations with their own surprising properties.

“A mound of foam is essentially a solid,” Brangwynne said. “You can push on it and it deforms, and when you take your finger away it springs back into shape. You’ve taken something that is 95 percent gas — it’s mostly air — and 5 percent liquid, and you’ve combined those in such a way that you get a solid.”

Correct biological function depends on transitions between these phases of matter. For example, your blood — typically a free-flowing liquid — clots to form a protective scab. However, these transitions can cause problems, for instance when an internal blood clot causes a stroke.

Likewise, the liquid inside each cell — the cytoplasm — regularly goes through local phase transitions, some of which are disruptive. This issue is linked to neurodegenerative diseases, including Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease). In these cases, proteins aggregate and spontaneously transition from a liquid phase into a sticky, solid-like state, prohibiting normal function in the brain or nervous system. These phase transitions are also thought to be involved in controlling cell size and growth, and thus diseases such as cancer.

Nucleoli from amphibian egg cells

Researchers in the Brangwynne lab use nucleoli from amphibian egg cells to study the role of gravity in determining the size of living cells. IMAGE COURTESY OF CLIFFORD BRANGWYNNE LAB

Brangwynne’s research focuses on gaining a better understanding of these living states of matter, and how they can be manipulated. Over the past few years, his group has published several studies exploring the molecules that control intracellular phase transitions and how the living matter within a cell affects gene regulation and cell size.

In one particularly exciting study, graduate student Marina Feric discovered that liquid-phase droplets of RNA and protein are biophysically linked to cell size through the force of gravity. Brangwynne, who receives support from the National Science Foundation (NSF) and the National Institutes of Health (NIH), is optimistic that these fundamental studies will lead to medical applications. “We’re certainly hoping to use our findings to perturb these systems and keep cells in a healthier state,” he said.

Swimming upstream

Like Brangwynne, Professor Howard Stone followed the flow of ideas from an area of engineering — fluid mechanics — to biology. “The living world involves flow almost by definition,” said Stone, who is the Donald R. Dixon ’69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering. “You circulate blood, you breathe streams of air in and out, you sweat to regulate temperature. If you study fluid mechanics, and if you’re somewhat open-minded, it’s easy to stumble across biological problems.”

One of the biological problems that caught Stone’s attention is how bacteria move in a fluid. Moving through water is far more difficult for bacteria than it is for a human. For single-celled creatures a millionth of a meter long, the force of friction dominates their ability to swim in a given direction. Instead, bacteria are usually just carried along for the ride.

Image of lungs

“The living world involves flow almost by definition.” –Howard Stone, the Donald R. Dixon ’69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering

The dominance of friction led to a discovery in Stone’s lab four years ago by visiting graduate student Yi Shen, who found that P. aeruginosa, a dangerous pathogen sometimes found in hospitals, can move against a current. The bacterium loses its flagellum — a long tail for swimming — when it adheres to a surface, which for many cells dictates the end of mobility. Yet P. aeruginosa can drag itself along a wall of, for example, a branched medical tube, by its small, tentacle-like pili, which are strong enough to resist the force of friction.

After observing this phenomenon, Stone and his collaborators — Professor of Molecular Biology Zemer Gitai; Albert Siryaporn, an associate research scholar in molecular biology; and Kevin Minyoun Kim, a graduate student in chemistry — began researching this behavior in systems mimicking the human body.

“Your blood vessels have branches. Your lungs are branched. We’ve made model branched systems and used a pump — like a heart — to drive fluid through it,” Stone said. “Bacteria inoculated into this flow sometimes end up in places you wouldn’t expect, and that, at this time, a simulation would never predict.” This basic research, which is supported by NSF, may allow us to better anticipate the movements of pathogens — in our bodies or our environments — in order to prevent infection and contamination.

Fluid environment

Bacteria are single-celled organisms that can form colonies, but a more sophisticated arrangement occurs in our own bodies, where huge communities of cells organize into tissues and organs. Celeste Nelson, an associate professor of chemical and biological engineering, studies the fetal development of these organs, which depends on the fluid environment in which they form.

One of the organs that forms in a fluid environment is the lung. A fetus’s lungs are filled with fluid during gestation. Nelson uses tissue cultures — parts of organs grown in laboratory dishes — and manipulates the speed and pressure of tiny streams of liquid that are directed onto the growing lung cells by small tubes.

Nelson has discovered that the higher the pressure of this fluid in the fetal lung, the more quickly the lungs develop, whereas lower pressure leads to slower development. Several congenital disorders can derail lung development, and Nelson’s work — which is supported by NIH, NSF, the David and Lucile Packard Foundation, the Camille and Henry Dreyfus Foundation, the Burroughs Wellcome Fund, the Essig Enright Family Foundation, and Princeton’s Project X, which provides seed funding for unconventional research — may improve our ability to diagnose such problems early.

The lungs, kidneys, mammary glands and other organs develop through a branched structure, which is an efficient space-filling strategy for functions that require maximum surface area. This exponential branching pattern is a highly reproducible selfassembly process, and in Nelson’s opinion, the forest of alveoli in the lungs is the most beautiful example. “The 23 generations of branches means several hundred million paths,” said Nelson. “Every one of those paths is needed for efficient diffusion of oxygen into the infant blood stream immediately after birth. “What’s amazing,” she said, “is that all of the branches in my lungs look exactly like the branches in your lungs.”

Lung image

Lung tissue extracted from a reptile embryo helps the Nelson lab study the effect of the fluid environment on lung development.

Nelson’s lab also studies a behavior in cancer cells called reversion, which — if it could be induced — would turn many cancers into benign, treatable illnesses. She collaborates with Derek Radisky, a researcher at the Mayo Clinic in Jacksonville, Florida. For Nelson, who started studying breast cancer while a postdoctoral fellow, the body’s organ systems have a mechanical elegance.

Timing is everything

Stanislav Shvartsman is as fascinated by the chemical aspects of development as Nelson is by the mechanical aspects. His research focuses on embryogenesis, the very early stages of fetal development.

“When you want to bake a cake, it’s not enough to say that you need eggs and milk and flour,” said Shvartsman, a professor of chemical and biological engineering and the Lewis-Sigler Institute for Integrative Genomics. “Knowing the ingredients, and even knowing the sequence in which you add these ingredients — which is what we know from genetics — is not enough to bake a cake that tastes good.”

When the recipe — the proper quantities of chemicals released by the cells of the embryo at the proper times — isn’t followed exactly, there are consequences for the developing organism. For example, a large class of developmental abnormalities, known as RAS-opathies, is associated with asymmetry in the craniofacial complex, stunted height, congenital heart defects, developmental delays and other issues. Such defects are observed in one in every thousand births and are believed to be caused by mutations in genes of the Ras-MAPK pathway.

Biologists know which genes are mutated, and even where to find these genes on our DNA. What they don’t know is why these particular mutations lead to a distinct set of clinical features. To find out, researchers turn to organisms that macroscopically look very different from us — such as bacteria and worms — but are very similar at the cellular level. Shvartsman’s research group, which is supported by NIH and NSF, uses the fruit fly to study embryogenesis.

Initially, the handful of cells that make up an embryo are all identical. By the time of birth, that homogenous handful will have given rise to brain, nerve, heart, blood and every other kind of cell required for a living, breathing organism. In order to differentiate into the right kind of cell at the right time, and to arrange into the correct three-dimensional shape, the embryonic cells have to communicate. They speak to each other through a language of chemical signals.

The signals are actually protein molecules, Shvartsman said. A protein released by one cell attaches to a receptor protein embedded in the surface of a neighboring cell. That surface protein reacts by changing shape, and in turn changing the internal environment of its cell. In this way cells “hear” each other. At any given time multiple cells are releasing various proteins, and the combination of signals floating through the embryonic environment tells a cell what to become, or when to divide to make more of itself.

To crack the code, Shvartsman is looking at one signal at a time, beginning with a set of proteins that is well understood genetically thanks to the work of such Princeton biologists as Gertrud Schüpbach, the Henry Fairfield Osborn Professor of Biology. By controlling the amount of these proteins released in the fly embryo, Bomyi Lim, a former graduate student in Shvartsman’s lab and now a postdoctoral research associate at the Lewis-Sigler Institute for Integrative Genomics, has discovered the minimum dosage necessary for proper structural development. This is the first step in a long process, but it is a milestone, and Shvartsman is excited about continuing the process. “It’s very exciting to work in a field where there’s no risk of ever saying, ‘This is the end of the times-table. There is no more material to learn,’” he said.

Image of fruit fly embryo structure

The image shows thin slices of a part of fruit fly embryos where stem cells turn into mature eggs. Created by graduate students Yogesh Goyal and Bomyi Lim and postdoctoral researcher Miriam Osterfield in the laboratory of Stanislav Shvartzman, the image was selected for display in Princeton’s 2014 Art of Science competition.

Some assembly required

Brangwynne views embryogenesis as the epitome of self-assembly, the process by which small, disorganized components interact based on simple rules to form complex structures without human intervention. A classic example is the snowflake, a delicate crystalline jewel formed in midair as water molecules freeze. Engineers have been trying to take advantage of self-assembly for some time — often in Brangwynne’s field of materials science — where time and money could be saved if certain synthetic materials would form on their own in a solution, rather than being painstakingly put together atom by atom.

“The embryo of an organism like C. elegans essentially starts out as just a bag of molecules,” Brangwynne said. Once the egg is fertilized, it begins to organize, and the unstructured soup of molecules turns into a wriggling worm. “There’s absolutely nothing that human engineering can do that comes anywhere close to what I just described takes place in embryos all the time,” Brangwynne said.

While Princeton scientists are importing methods and paradigms from engineering disciplines to biology, they see a two-way street, recognizing that biology itself has methods to share.

“We would like to learn how nature, through hundreds of millions of years of evolution, has generated these systems that are just completely unbelievable in their level of sophistication,” Brangwynne said. “It’s as if we’ve been visited by an alien civilization that was millions of years more advanced than us. The first thing we would do would be to take a really close look at that spaceship. We’d try to figure out what it is made of, what are the principles that govern its flight and its control systems. That’s what we are doing with biological systems.”

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Read more about bioengineering at Princeton:

Lab on a chip is smaller than a penny.Computer chip for point-of-care diagnosis

Assistant Professor Kaushik Sengupta and his team are developing a computer chip-based diagnostic system, which is smaller than a penny but contains hundreds of different sensors for simultaneous detection of disease-causing agents.

‘Jack’ Hoang Lu researches nanoparticles for drug deliveryTiny delivery capsule for new drugs

Graduate student ‘Jack’ Hoang Lu works on engineering nanoparticles for targeted drug delivery and diagnostics in the laboratory of Robert Prud’homme, professor of chemical and biological engineering.

Benjamin TienEngineering health solutions for all

Benjamin Tien, Class of 2015, conducted senior thesis research on nanoparticles for treatment of infections. Now he is a Fulbright scholar working to develop a treatment for excessive bleeding after childbirth.

Janet Currie investigates the building blocks of children’s success

Janet Currie

Janet Currie PHOTO BY DENISE APPLEWHITE

By Michael Hotchkiss

TRAINED AS A LABOR ECONOMIST, Janet Currie earned her doctorate at Princeton by studying strikes and arbitration. But as she began her academic career in the late 1980s, she shifted her focus to examining the building blocks of success for children, as well as the stumbling blocks that can get in their way.

While the topics are very different, Currie said both benefit from research by economists. “I realized that economics is really more of a method, or a way of thinking, than a set of topics, and I have implemented that by working on issues that can benefit from the tools of economics research,” she said.

Over the nearly three decades since, Currie has used the methods of an economist, her analytical skills and an openness to new ideas to offer important insights into the health and well-being of children. In the terms of economics, she studies the factors that affect children’s human capital — the intangible assets such as health, skills and knowledge that play a role in life outcomes.

Today the Henry Putnam Professor of Economics and Public Affairs at Princeton and chair of the Department of Economics, Currie has tackled research on a wide range of topics, including socioeconomic differences in child health, environmental threats to children’s health and the long-term effects of poor health in early childhood.

Beyond the individual findings, Currie said, are broader lessons.

“One would be that very early life is important,” she said. “That is now pretty well accepted and has had an impact on policy, but at the time I was starting to do this research that wasn’t so widely appreciated. Another kind of general conclusion is that pollution at lower levels than Environmental Protection Agency thresholds for concern has measureable and detectable health effects.”

Currie joined the Princeton faculty in 2011 from Columbia University. Previously, she was on the faculty at the University of California-Los Angeles and the Massachusetts Institute of Technology.

At Princeton, Currie is director of the Center for Health and Wellbeing, which fosters research and teaching on aspects of health and well-being in developed and developing countries. She is also a senior editor of the Future of Children, a publica- tion that translates social science research about children and youth into information that is useful to policymakers, practitioners and other nonacademic audiences.

Sara McLanahan, a Princeton sociologist who works with Currie on projects including the Future of Children and shares many of her research interests, said Currie is “one of the most outstanding economists in the country who is doing work on child health.” And, McLanahan added, Currie’s impact goes beyond her research.

“She’s just very willing to give her time and be generous,” said McLanahan, the William S. Tod Professor of Sociology and Public Affairs. “She’s a straight shooter. She tells you what she thinks. She does more than her share, and she wants it to be done right. She’s just a great positive force.”

An economist’s approach

Currie, who earned her bachelor’s and master’s degrees in economics from the University of Toronto before coming to Princeton for her doctoral studies, said several aspects of economics make it useful in studying children and their outcomes.

Among them: a tradition of using models to frame issues, an emphasis on measurement and a focus on establishing causal relationships.

Often, she has applied these principles in natural experiments, which are observational studies where conditions outside a researcher’s control randomly assign some people to an experimental condition and others to a control condition.

For example, interest in the impact of pollution on infant health led Currie and Reed Walker, then a graduate student at Columbia and now an assistant professor at the Haas School of Business at the University of California-Berkeley, to examine the effect of introducing electronic toll collection on the health of children born to mothers who lived near toll plazas. They found that the switch to electronic toll collection, which greatly reduced traffic congestion and vehicle emissions near toll plazas, was associated with a decline in premature and low-birth-weight babies born to those mothers.

That research depended on identifying the roll-out of electronic toll collection as a potential natural experiment, gathering pollution data for the area of toll plazas, and mining birth records for the necessary information about the residences of mothers and birth outcomes.

In another natural experiment, Currie and Maya Rossin-Slater of Columbia used birth records from Texas and meteorological information to identify children born in the state between 1996 and 2008 whose mothers were in the path of a major tropical storm or hurricane during pregnancy. They found that expectant mothers who dealt with the strain of a hurricane or major tropical storm passing nearby during their pregnancy had children who were at elevated risk for abnormal health conditions at birth.

Keeping an open mind

Hannes Schwandt, who has worked closely with Currie during three years as a postdoctoral research associate at the Center for Health and Wellbeing, said another important aspect of Currie and her work is her openness to new ideas.

“On the one hand, she has this great detailed expertise, given all the work she has done,” Schwandt said. “At the same time, she’s always open to new questions. I think combining her expertise with this view for broad, new directions is what makes her so special.”

Take a paper he and Currie published in 2014 on the effect of recessions on fertility. The idea began, Schwandt said, with a discussion they had about evidence that babies born during recessions are generally healthier than those born in better times.

“Janet said we need to step back and look at fertility — who is giving birth — instead of focusing on the health of babies,” Schwandt said. “She immediately made the connection that in the news there is always a discussion that there is decline in fertility during recessions. But no one really knew the long-term effect.”

After examining 140 million births over 40 years, Currie and Schwandt found that recessions are linked to an increase in the number of women who remain childless at age 40.

What’s ahead

Currie is continuing to pursue ways to address issues relating to children and their development.

One project is looking for new evidence of the impact of lead exposure on children and their educational outcomes in Rhode Island. By matching birth records, lead-test results and school records, Currie is examining the impact of a program to reduce children’s exposure to lead.

“One of the really interesting things about this research, I think, is that the program to reduce lead exposure seems to have been pretty effective,” Currie said.

Because African American children were more likely to live in areas with high lead levels, the program brought their lead levels down more quickly than those of white children. At the same time, Currie said, the gap in standardized test scores between the groups narrowed.

The research could offer new clues about the role lead exposure plays in the lower test scores typically recorded by students who live in inner-city areas where lead exposure is more common, Currie said.

Another work in progress takes advantage of the implementation of congestion pricing in Stockholm, which levies a tax on most vehicles entering and exiting the city’s center, to measure the impact of traffic — and the resulting pollution — on child health. A third is examining state-by-state differences in smoking patterns among pregnant women and the relationship between smoking among pregnant women and low-birth-weight births.

A topic she would like to address in future work: mental health.

“I’m interested in that for a lot of different reasons,” she said. “If you look at the U.S. economy, mental health is the leading cause of lost work. That’s because it tends to strike people who are of working age, whereas a lot of other health conditions are more for older people. It’s important from an economic point of view. It also seems to be very related to a lot of learning issues.”

Over the past 20 years, Currie said, a raft of new psychiatric medications has come on the market, many of which are not well understood, and prices are rising.

“It seems like there’s this huge black box of things that are happening and no one is really studying, and there’s not very good data on it,” she said. “That’s something I’ve been struggling with for a while, how to get some purchase on that problem.”

Valued as a mentor

Currie is also widely recognized for her work with young researchers and her advocacy for them.

“In addition to all the work she does as a top economist, being willing to work with students is a great benefit,” McLanahan said. “Having someone do so well and be so generous is important, especially for the next generation of female economists.”

In spring 2015, Currie received a Graduate Mentoring Award from the McGraw Center for Teaching and Learning. Graduate students described Currie as insightful and readily available to help aspiring researchers develop their ideas and present them publicly.

Molly Schnell, a Ph.D. candidate in economics, said Currie is so generous with her time “that she seems to defy the principle of scarcity.”

In particular, she pointed to Currie’s willingness to co-author papers with graduate students.

“Learning to develop a paper by working through the process with an established researcher is a formative experience, and Janet makes sure that her students have this opportunity,” Schnell said.

Schwandt said Currie has helped him grow more confident in tackling new topics.

“One thing I’ve learned from her is not to worry too much whether other people think something is economics or not,” he said. “She always says: ‘First, who defines what economics is? And second, why do we really care so long as it is a really important question and we can help answer it?’”

Professor Janet Currie’s research uses the tools of economics research to study issues in children’s health. Among her findings:

E-Z Pass Research

 

Expectant mothers

 

 

Foreclosure research

 

 

 

Fertility research

 

 

 

 

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Laser device may end pin pricks, improve health for diabetics

Diabetes sensor

Claire Gmachl, Kevin Bors and Sabbir Liakat test a laser-based glucose-sensor. (Photo by Frank Wojciechowski)

PRINCETON RESEARCHERS have developed a way to use a laser to measure people’s blood sugar, and, with more work to shrink the laser system to a portable size, the technique could allow diabetics to check their condition without pricking themselves to draw blood.

“We are working hard to turn engineering solutions into useful tools for people to use in their daily lives,” said Claire Gmachl, the Eugene Higgins Professor of Electrical Engineering and the project’s senior researcher. “With this work we hope to improve the lives of many diabetes sufferers who depend on frequent blood glucose monitoring.”

In an article published June 23, 2014, in the journal Biomedical Optics Express, the researchers describe how they measured blood sugar by shining their specialized laser — called a quantum cascade laser — at a person’s palm. The method exceeded the accuracy required for glucose monitors, said Sabbir Liakat, the paper’s lead author and a graduate student in electrical engineering. The team is now working on making the device smaller and portable.

Besides Liakat and Gmachl, researchers included Princeton undergraduate students in electrical engineering Laura Xu (Class of 2015), Callie Woods (Class of 2014) and Kevin Bors (Class of 2013); and Jessica Doyle, a teacher at Hunterdon Regional Central High School. Support for the research was provided in part by the Wendy and Eric Schmidt Foundation, the National Science Foundation, Daylight Solutions Inc., and Opto-Knowledge Systems.

–By John Sullivan