University of Washington bioengineers have developed the first structure to grow small human blood vessels, creating a 3-D test bed that offers a better way to study disease, test drugs and perhaps someday grow human tissues for transplant.

The findings are published online this week in the Proceedings of the National Academy of Sciences.

"In clinical research you just draw a blood sample," said first author Ying Zheng, a UW research assistant professor of bioengineering. "But with this, we can really dissect what happens at the interface between the blood and the tissue. We can start to look at how these diseases start to progress and develop efficient therapies."

Researchers made a functional microvessel that spells the letters "UW." The white bar measures 100 micrometers, about the width of a human hair.

Y. Zheng, U. of Washington

During a period of two weeks, the endothelial cells grew throughout the structure and formed tubes through the mold's rectangular channels, just as they do in the human body.

When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network. A similar system could supply blood to engineered tissue before transplant into the body.

After joining the UW last year, Zheng collaborated with the Puget Sound Blood Center to see how this research platform would work to transport real blood.

Engineered microvessels can form bends and T-junctions, like this one. The blue dots are the nuclei of the cells in the vessel walls, and the red lines are the cell junctions. Smooth muscle cells (green) wrap and tighten around the vessels, just as they do in the human body.

Y. Zheng, U. of Washington

The engineered vessels could transport human blood smoothly, even around corners. And when treated with an inflammatory compound the vessels developed clots, similar to what real vessels do when they become inflamed.

The system also shows promise as a model for tumor progression. Cancer begins as a hard tumor but secretes chemicals that cause nearby vessels to bulge and then sprout. Eventually tumor cells use these blood vessels to penetrate the bloodstream and colonize new parts of the body.

When the researchers added to their system a signaling protein for vessel growth that's overabundant in cancer and other diseases, new blood vessels sprouted from the originals. These new vessels were leaky, just as they are in human cancers.

"With this system we can dissect out each component or we can put them together to look at a complex problem. That's a nice thing—we can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do the endothelial cells interact with their surroundings, and how do these interactions affect the vessels' barrier function? We have a lot of degrees of freedom," Zheng said.

The system could also be used to study malaria, which becomes fatal when diseased blood cells stick to the vessel walls and block small openings, cutting off blood supply to the brain, placenta or other vital organs.

"I think this is a tremendous system for studying how blood clots form on vessels walls, how the vessel responds to shear stress and other mechanical and chemical factors, and for studying the many diseases that affect small blood vessels," said co-author Dr. José López, a professor of biochemistry and hematology at UW Medicine and chief scientific officer at the Puget Sound Blood Center.

Future work will use the system to further explore blood vessel interactions that involve inflammation and clotting. Zheng is also pursuing tissue engineering as a member of the UW's Center for Cardiovascular Biology and the Institute for Stem Cell and Regenerative Medicine.

Other co-authors are UW physics senior Samuel Totorica; Abraham Stroock, Michael Craven, Nak Won Choi, Michael Craven, Anthony Diaz-Santana and Claudia Fischbach at Cornell; Junmei Chen at the Puget Sound Blood Center; and Barbara Hempstead at Weill Cornell Medical College.

The research was funded by the National Institutes of Health, the American Heart Association, the Human Frontier Science Program and Cornell University.

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For more information, contact Zheng at 206-543-3223 or yingzy@uw.edu.

A Tokyo museum book contains page after page of the strings of DNA code letters A,G,C and T found in the human genome. A single letter change might influence health risks.

Ben Casey

“This is a dramatic example of how recent human history has profoundly shaped patterns of genetic variation,” said Joshua Akey, University of Washington associate professor of genome sciences and a senior author of the study. His lab studies the genetic architecture behind differences among humans (as well as among other species) and the mechanisms of evolutionary change.

Although so-called single nucleotide variants are rare, they may influence a person’s resistance or susceptibility to common diseases, like heart or lung trouble or blood problems. The rarity of each specific variation means that scientists will often need to study DNA samples from very large numbers of people to draw any genetic links to these disorders. Researchers already realize that commonly occurring gene variants have only a modest role in the complex medical conditions with the most public health repercussions.

In this week’s paper, “Evolution and Functional Impact of Rare Coding Variations from Deep Sequencing of Exomes,” investigators described their study of the protein-coding sections of genomes from almost 2,440 individuals. The participants were 1,351 people of European extraction and 1,088 of African ancestry.

The study is a first step toward understanding how rare genetic variants contribute to some of the leading chronic illness causes of death in the world. It was conducted as part of the mission of the Seattle GO at the University of Washington and the Broad GO at Harvard University and MIT, both funded by the National Institute of Health’s National Heart Lung and Blood Institute Exome Sequencing Project. The exome consists of the protein-coding regions of the genome.

The overall project encompasses a great many individuals who have distinct traits, such as heart attacks before old age, strokes, or a high body mass index, to discover the genes and molecular mechanisms behind these conditions. Low cost, rapid sequencing of whole genomes is on its way to becoming clinically feasible. The information gleaned would be more useful if statistical and experimental methods could more accurately identify gene variations that regulate biological processes and produce functionally significant proteins. Such methods would link gene variations to disease causes and provide information for preventing and treating diseases.

The other senior author of the paper from the Exome Sequencing Project is Michael J. Bamshad, University of Washington professor of pediatrics in the Division of Genetic Medicine. Researchers from eight institutions across the nation collaborated.

The group sequenced and compared 15,585 human protein-coding genes. They located more than a half-million single-letter DNA code variations in their sample populations. The majority of these variations arose recently in human evolutionary history and so were rare, novel, and specific either to the African or the European study populations, the researchers discovered.

The researchers went on to pick just those single-letter variations in the DNA that might affect the functions of proteins. Alterations in protein functions are among the key ways genetic differences spin into disease traits. They estimated that a little more than 2 percent of the approximately 13,600 single nucleotide variations each person carried, on average, influenced the function of about 313 genes per genome. More than 95 percent of the single-letter code changes predicted to be functionally important were rare in the overall study population.

How did so many rare variations affecting protein function arise in the human genetic code? The researchers suggest that this excess of rare variations is due to a combination of demographic and evolutionary forces. Both European and African populations grew exponentially beginning around 10,000 years ago, but in the past 5,000 years growth rates accelerated leading to the billions of people living today.

The dramatic recent increase in population size has therefore profoundly influenced the spectrum of protein-coding variation present in humans. The scientists calculated the mean average of novel, single-letter code variations in their study subjects: 549 per individual overall. People of African descent had about twice the number of new variations compared to those of European descent, or 762 versus 382.

The researchers measured the effects of natural selection on rare coding variation. To do so, they also brought in genetic details from genes highly specific to humans relative to chimps and macaques to look for what are called “selective sweeps.” A selective sweep occurs when natural selection increases the frequency of a beneficial variant in a population. The beneficial variant doesn’t travel alone. Nearby genetic material is swept along with it. Included among the genes the scientists culled out as affected by positive selection were those related to the sense of smell and to the use of energy.

The researchers also learned that most of the protein-coding variations identified in their study were predicted to be harmful. Rare variation contributes not simply to each individual’s uniqueness, but also to the  risk for life-shortening illnesses.

What are the implications of these findings for understanding disease and advancing personalized medicine? Before answering, the researchers pointed to present limitations in robustly identifying functional important gene variation.

“Nevertheless,” they said, “there was considerable rare genetic variation among individuals that is predicted to be functional, which could explain variability in disease risk and in drug response.” The researchers would like more powerful tests to detect the effects of rare genetic variations on human health. They suggest that accounting gene-by-gene might improve research methods. They added that the population-specific nature of most of the single-letter code changes will make it challenging to replicate disease associations with a variant across the world’s people.

In addition to Akey and Bamshad, other researchers on the study were Jacob A. Tennessen, Timothy D. O’Connor, Wenqing Fu, Sean McGee, Mark J. Rieder, and Deborah A. Nickerson, all of the UW Department of Genome Sciences; Abigail W. Bigham of the UW Department of Pediatrics; Eimear E. Kenny, Simon Gravel and Carols D. Bustamante of Stanford University; Ron Do Stacey Gabriel, David Altshuler, and Shamil Sunyaev of the Broad Institute of MIT and Harvard University; Xiaoming Liu and Eric Boerwinkle , of the Texas Health Sciences Center in Houston; Goo Jun, Hyun Min Kang and Goncalo Abecasis of the University of Michigan; Daniel Jordan of the Division of Genetics at Brigham & Women’s Hospital in Boston; and Suzanne M. Leal of the Department of Molecular and Human Genetics at Baylor College of Medicine. The Center for Human Genetic Research at Massachusetts General Hospital and the Human Genome Sequencing Center at Baylor College of Medicine also contributed to this study.

Drops of red and blue liquid move along the upper and lower surface of the vibrating UW platform at speeds up to 1 inch per second. This combined image shows drops as they move toward the center and merge.

Karl Bohringer, UW

"This allows us to move drops as far as we want, and in any kind of layout that we want," said Karl Böhringer, a UW professor of electrical engineering and bioengineering. The low-cost system, published in a recent issue of the journal Advanced Materials, would require very little energy and avoids possible contamination by diluting or electrifying the samples in order to move them.

The simple technology is a textured surface that tends to push drops along a given path. It's inspired by the lotus effect – a phenomenon in which a lotus leaf's almost fractal texture makes it appear to repel drops of water.

"The lotus leaf has a very rough surface, in which each big bump has a smaller bump on it," Böhringer said. "We can't make our surface exactly the same as a lotus leaf, but what we did is extract the essence of why it works."

A drop of liquid sits on the textured silicon surface that has arced rungs to guide the drop, and a grid of pillars to keep the drop in the channel.

Karl Bohringer, UW

Researchers used an audio speaker or machine to vibrate the platform at 50 to 80 times per second.  The asymmetrical surface moves individual drops along predetermined paths to mix, modify or measure their contents. Changing the vibration frequency can alter a drop's speed, or can target a drop of a certain size or weight.

"All you need is a vibration, and making these surfaces is very easy. You can make it out of a piece of plastic," Böhringer said. "I could imagine this as a device that costs less than a dollar – maybe much less than that – and is used with saliva or blood or water samples."

A close-up of the UW surface showing the arc edges and adjacent pillars.

Karl Bohringer, UW

The type of system is known as a "lab in a drop": all the ingredients are inside the drop, and surface tension acts as the container to keep everything together.

A student tried using a smartphone's speaker to vibrate the platform, but so far a phone does not supply enough energy to move the drops. To better accommodate low-energy audio waves, the group will use the UW's electron beam lithography machine to build a surface with posts up to 100 times smaller.

"There’s good evidence, from what we’ve done so far, that if we make everything smaller then we will need less energy to achieve the same effect," Böhringer said. "We envision a device that you plug into your phone, it’s powered by the battery of the phone, an app generates the right type of audio vibrations, and you run your experiment."

Co-authors of the paper are former UW undergraduate Todd Duncombe and former UW graduate student Yegȃn Erdem, both at the University of California, Berkeley; former UW postdoctoral researcher Ashutosh Shastry, now at Corium International in Menlo Park, Calif.; and Rajashree Baskaran, a UW affiliate assistant professor of electrical engineering who works at Intel Corp.

The research was funded by the National Science Foundation, the National Institutes of Health, Intel and the UW's Technology Gap Innovation Fund.

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For more information, contact Böhringer at 206-221-5177 or karl@ee.washington.edu.

Researchers at the University of Washington have studied vessel walls and found the cells pull more tightly together, reducing vascular leakage, in areas of fast-flowing blood. The finding could influence how doctors design drugs to treat high cholesterol, or how cardiac surgeons plan their procedures.

Their paper will be published in an upcoming issue of the American Journal of Physiology - Heart and Circulatory Physiology.

A layer of cells that coat the pulmonary artery grown on a bed of silicon microposts. After being exposed to a rapid flow, the cells make tighter junctions and tug more strongly on their neighbors.

Nathan Sniadecki, University of Washington

"Our results indicate that these cells can sense the kind of flow that they’re in, and structurally change how they hold themselves together," said lead author Nathan Sniadecki, a UW assistant professor of mechanical engineering. "This highlights the role that cellular forces play in the progression of cardiovascular disease."

It's known that the arteries carrying blood are leakier in areas of slow flow, promoting cholesterol buildup in those areas. But medical researchers believed this leakage was mostly biochemical – that cells would sense the slower flow and modify how proteins and enzymes function inside the cell to allow for more exchange.

The new results show that, like a group of schoolchildren huddling closer in a gust of wind, the cells also pull more tightly together when the blood is flowing past.

"The mechanical tugging force leads to a biochemical change that allows more and more proteins at the membrane to glue together," Sniadecki said. "We're still trying to understand what's happening here, and how mechanical tugging leads more proteins to localize and glue at the interface."

Sniadecki's group looks at the biomechanics of individual cells. For this experiment, they grew a patch of human endothelial cells, the thin layer of cells that line the inner walls of arteries and veins and act as a sort of nonstick coating for the vessels' walls. They grew the patch on an area about the width of a human hair, manufactured with 25 by 25 tiny flexible silicon posts.

A simulation of the posts that support the heart cells. Light blue is 1 nanometer of deflection, while dark red means the post is deflected by 2.5 nanometers.

Nathan Sniadecki, University of Washington

Knowing how cells respond to blood flow could help find new drugs to promote this tugging between cells. Better understanding of the interaction between blood flow and heart health could also guide surgeries.

"People could do simulations so a surgeon goes, ‘Ah, I should cut here versus over here, because that reconstruction will be a smoother vessel and will lead to fewer complications down the line, or as I put this stent in, put it here and make it more aerodynamic in design,'" Sniadecki said.

Co-authors are Lucas Ting, Joon Jung, Benjamin Shuman, Shirin Feghhi, Sangyoon Han, Marita Rodriguez in the UW's department of mechanical engineering, and Jessica Jahn at UW Medicine.

The research was funded by the National Institutes of Health, the National Science Foundation, the UW Medical Student Research Training Program and the UW Royalty Research Fund.

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For more information, contact Sniadecki at 206-685-6591 or nsniadec@uw.edu.

The researchers have been studying ASD in children who have no family history of this or related impairments - so called “sporadic autism” - and also why autism varies in its symptoms and severity. By focusing  on “sporadic autism”, the researchers sought to evaluate a specific genetic model for ASD risk, namely the appearance of new mutations (termed de novo) in children with ASD that were not found in either parent.

Dr. Brian O'Roak, a postdoctoral fellow in genome sciences, led the study of autism mutations in children from families with no previous history of autism.

Clare McLean

By uncovering new gene mutations that disrupt the function of proteins, the researchers have discovered a pathway related to modifying chromatin – the tightly coiled spools of DNA in the cell -- and  to regulating genes in the brain and nervous system. Various changes in this pathway contribute to children developing autism in different ways.  Mutations in this pathway also may contribute to a variety of childhood intellectual, social, and psychiatric disabilities, with implications beyond autism.

To identify these new mutations, the researchers used the latest sequencing technologies and analytical methods to determine the sequence of the protein-coding portion of the human genome, called the “exome”, in family trios (father, mother, and child). This approach was piloted this past  year at the University of Washington with an initial set of 20 autism families. The pilotdemonstrated  the  technical feasibility and potential impact of this approach. (see http://www.washington.edu/news/articles/sporadic-mutations-identified-in-children-with-autism-spectrum-disorders).

For the current study, the researchers expanded the research to include 677 individuals from 209 families with a single child with autism. They also sequenced the exomes of 50 unaffected brothers and sisters. In the newly reported results, 248 de novo mutations were validated, and 120 of these were classified as severe. These were predicted to produce, for example, proteins that were truncated or malfunctioning.   The researchers then narrowed in on 60 top candidates most likely to contribute to autism risk, based on the nature of the mutation, functional evidence, or previous studies.

“It is important to point out that in each generation there is on average one new coding mutation per child and not all of these will cause developmental problems. However, in the case of children with autism, what we are finding is disruptions in many genes that are known to directly interact and also look similar to genes previous associated with autism,” said  Brian J. O’Roak, a senior fellow in the Department of Genome Sciences working with senior authors Dr. Jay Shendure and Evan Eichler. In fact, researchers found that 49 of the genes mutated had products known to directly interact by forming a highly interconnected network.  Interestingly, many of the proteins in this pathway are important in terms of remodeling chromatin—changing the way DNA is packaged in the cell-- and controlling the expression and function of other genes and proteins.  These protein pathways are thought to be critical in brain cell formation, brain cell connections, and nerve-cell signaling.

Having this large data set also allowed the researchers to evaluate the parental source of these new mutations - that is, whether they came from the sperm of the father or egg of the mother. Their analysis revealed that the new mutations were overwhelming paternal in origin (in a ratio of 4:1) Their results confirmed a prediction population geneticist J.B.S. Haldane made in in 1935. Moreover, the new mutations occurred at a rate that correlated with the age of the father.  These findings, they said, support other studies that show older fathers have a slightly increased risk of having a child with an autism spectrum disorder.

What is also very clear from this study and two additional studies appearing concurrently in the same issue of Nature is that autism risk mutations are scattered across many genes. One of the other studies was led by Mount Sinai Medical Center in New York, the second by Yale University in New Haven.

In the UW study, recurrent protein-altering mutations were discovered in only two genes, NTNG1, and CHD8.  The data suggest that, at the molecular level, thare are many different forms of autism and that the term “autism spectrum disorder” is better thought of as an umbrella disorder with many root causes.  The authors predict that although no single gene will account for more than 1 percent of autism, collectively all of these rare mutations will account for much of the genetic basis of the disease.

Brian O'Roak, Evan Eichler (seated) and Jay Shedure (right) in one of the UW labs where researchers search for sporadic mutations associated with autism.

Clare McLean

While this level of complexity is a major challenge for the field, the authors are already working on a solution using next-generation sequencing approaches. To tackle this challenge, the researchers implemented a new cost-effective screening technology that allowed them to screen more than 2,500 inviduals for mutations in six genes in only a month. In so doing they found  strong evidence for the involvement of a glutamate receptor gene GRIN2B for a subset of cases with autism.  This same approach will allow the authors to screen all of the newly discovered genes to rapidly test which ones are truly disease-causing.

Among the other genes they discovered with de novo mutations in children with autism, several have been previously implicated in intellectual disability and developmental delay. This indicates, the authors said, that the divisions clinicians made between these various types of diseases in children may not readily translate into differences at the molecular level.  The researchers added that it is still uncertain whether there are subsets of people with autism who share a common or strongly related causative mechanism in their underlying molecular biology, or how large those groups might be.

In addition to O’Roak, Shendure, and Eichler, other researchers on the study were Laura Vives, Santhosh Girirajan, Emre Karakoc, Nik Krumm, Bradly P.Coe, Roie Levy, Arthur Ko, Choli Lee, Joshua D. Smith, Emily H. Turner, Ian B. Stanaway, Benjamin Vernot, Maika Malig, Carl Baker, Beau Reilly, Joshua M. Akey, Elhanan Borenstein, Mark J. Rieder, and Deborah A. Nickerson, all from the UW Department of Genome Sciences, and Rapheal Bernier, of the UW Department of Psychiatry and Behavioral Sciences. Eichler is also a investigator with the Howard Hughes Medical Institute, and Borenstein also holds appointments in the UW Department of Computer Science and Engineering and at the Santa Fe Institute.

This project was supported by the Simons Foundation Autism Research Initiative, the National Institutes of Health, and the Howard Hughes Research Institute.  The authors have declared competing financial interests, which are published with their Nature manuscript.

Pediatricians responded to case scenarios involving medical treatments for white and African American patients for four common pediatric conditions.

"We're talking about subtle, unconscious attitudes that are pervasive in society. Because these are unconscious attitudes, doctors aren't aware that their racial attitudes may affect their treatment decisions," said Janice Sabin, a UW research assistant professor in the Department of Biomedical Informatics and Medical Education, a part of UW's School of Medicine.

She is lead author of the study published online March 15 in the American Journal of Public Health.

Sabin's previous research showed that pediatricians display less unconscious race bias than other medical doctors or the general population. Still, unconscious beliefs can affect how doctors interact with patients, and the current study reveals that those attitudes can influence doctors' treatment decisions.

"Coupled with known racial and ethnic disparities in health care, our findings suggest that well-meaning physicians may unconsciously treat people differently in some areas of care," said Sabin.

Among the 86 pediatricians who participated in the study, 65 percent were female, 82 percent were white and 59 percent were medical residents or fellows. They completed three Implicit Association Tests to measure unconscious attitudes and beliefs.

The test was developed in 1998 by Anthony Greenwald, a co-author and a UW psychology professor. The test measures implicit attitudes by asking participants to quickly classify several series of words or visual images as they appear on a computer screen. The patterns of speeds in response to varied classification instructions can reveal automatically operating biases.

Sabin chose four conditions commonly treated by pediatricians – asthma, attention deficit hyperactivity disorder, urinary tract infections and pain. Case scenarios were created for each condition for both an African-American and a white patient.

For the asthma, ADHD and urinary tract infection case scenarios, doctors did not show an association between unconscious attitudes about race and treatment decisions for the two patients. However, recommendations for optimal pain treatment decreased for the African American patient as doctors' pro-white bias increased.

"Implicit biases are surprisingly pervasive, and in certain circumstances they can affect how people behave," Sabin said. She said her findings "indicate that more research should be done to see if unconscious biases affect real-world medical care and treatment decisions, especially for pain management."

"This is exactly the type of result that was anticipated by the Institute of Medicine's landmark 2002 Unequal Treatment study," Greenwald said. "That study and other studies found, among other indications of troubling health care disparities, underuse of pain medication for African American patients."

Because physicians are likely unaware of unconscious attitudes and beliefs and the unintended disparities that may result, incorporating awareness of personal bias and methods to avoid the influence of bias on decision-making into medical education, continuing medical education and training of health professionals is necessary for health sciences education, Sabin suggested.

The U.S. Department of Health & Human Services, Agency for Healthcare Research and Quality, the National Institute of Mental Health and a University of Washington Magnuson Health Scholars Award funded the study.

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For more information, contact Sabin at 206-616-9421 or sabinja@uw.edu.

The study was a randomized trial with 255 gun-owning households. An $80 locking metal gun cabinet was installed free of charge in the homes, with participants given a brief safety message and instructions on how to use the gun cabinet, including keeping the key in a secure place. The households were divided into two groups, with cabinet installation in the “early” group happening 12 months before installation in the “late” group.

To measure the effect of the gun cabinets, the household member most knowledgeable about the guns in the home took a 13-question survey about how the guns and ammunition were stored. The questions were asked by a researcher visiting the home before, and 12 and 18 months after installation of the gun cabinet.

When the study began,

•   93 percent of participating households reported at least one unlocked gun in the home;

• 89 percent reported unlocked ammunition.

One year after the study began, when early group homes had gun cabinets for 12 months but cabinets were not yet installed in late-group homes,

•     35 percent of households in the early group reported unlocked guns in the home;

•     89 percent of households in the late group, without gun cabinets, reported unlocked guns (declining to 35 percent, six months after receiving a cabinet);

•    35 percent of homes in the early group reported unlocked ammunition;

•     84 percent in the late group reported unlocked ammunition.

Grossman showed in a 2005 JAMA study on U.S. youth that safe firearm storage reduced the risk of unintentional injury and suicide. He conducted this work at UW Medicine’s Harborview Injury Prevention and Research Center, with which he is still affiliated. Alaska Native people have a suicide rate more than three times greater than white Americans. Among Alaska Native men aged 15 to 19, firearm-related suicides were more than 10 times higher than for U.S. white male teenagers in 2000–2006.

“We learned from a small, successful, community-based pilot project that installing gun cabinets in homes in an Alaskan Native village increased safe household firearm storage,”  Grossman said. “This current study showed conclusively that it can work in other rural Native villages, and the effects are quite durable over time.”

Further discussing the current study,  Grossman added: “This community-supported program to install gun cabinets in homes in rural Alaskan Native villages is feasible and acceptable and clearly reduces exposure of children and teens to unlocked guns and ammunition. If these results are maintained over time, gun-related injuries and deaths could be reduced in this population.”

The Alaska Native Tribal Health Consortium Injury Prevention Program estimates that over 300 gun safes have been placed in rural homes in the past four years. The Alaska Native Tribal Health Consortium provided initial support for the gun safe project in 2008, inviting tribal injury prevention and housing authority staff from regions with an established injury prevention program. From there, regions identified funding and determined how to implement the project locally.

In collaboration with multiple partners, healthy choices are promoted as a means to prevent injury and support community wellness. In addition to suicide prevention and gun safety, the Alaska Native Tribal Health Consortium Injury Prevention Program focuses on water safety, traumatic brain injury prevention and fall prevention. Education, advocacy and coalition-building are ways in which this is achieved.

Grossman is affiliated with UW Medicine’s Harborview Injury Prevention and Research Center and the UW School of Public Health. His co-authors were Helen Andon Stafford and Ryan Hill, who were at the Alaska Native Tribal Health Consortium at the time of this study; Thomas D. Koepsell, professor emeritus of epidemiology and health services at the UW School of Public Health; Kyla D. Retzer, formerly of the Yukon Kuskokwim Health Corporation and the Alaska Native Tribal Health Consortium and now at the National Institute for Occupational Safety and Health;  and Ward Jones of the Bristol Bay Area Health Corporation.

The Centers for Disease Control and Prevention and the Indian Health Service each provided funding for the study.

Rebecca Hughes is  senior media consultant for the Group Health Research Institute.

The researchers found that the wall of the aorta, the largest blood vessel carrying blood from the heart, exhibits ferroelectricity, a response to an electric field known to exist in inorganic and synthetic materials. The findings are being published in an upcoming issue of the journal Physical Review Letters.

Electrical response overlaid on the inner aortic wall.

Jiangyu Li, UW

“The result is exciting for scientific reasons,” said lead author Jiangyu Li, a UW associate professor of mechanical engineering. “But it could also have biomedical implications.”

A ferroelectric material is an electrically polar molecule with one side positively charged and the other negatively charged, whose polarity can be reversed by applying an electrical field.

Ferroelectricity is common in synthetic materials and used for displays, memory storage, and sensors. (Related research by Li and colleagues seeks to exploit ferroelectric materials for tiny low-power, high-capacity computer memory chips.)

In the new study, Li collaborated with co-author Katherine Zhang at Boston University to explore the phenomenon in biological tissues. The only previous evidence of ferroelectricity in living tissue was reported last year in seashells. Others had looked in mammal tissue, mainly in bones, but found no signs of the property.

The new study shows clear evidence of ferroelectricity in a sample of a pig aorta.  Researchers believe the findings would also apply to human tissue.

In subsequent work, yet to be published, they divided the sample into fibrous collagen and springy elastin and studied each one on its own. Pinpointing the source of the ferroelectricity may answer questions about how or whether it plays a role in the body.

“The elastin network is what gives the artery the mechanical property of elasticity, which of course is a very important function,” Li said.

Ferroelectricity may therefore play a role in how the body responds to sugar or fat.

Diabetes is a risk factor for hardening of the arteries, or atherosclerosis, which can lead to heart attack or stroke. The team is investigating the interactions between ferroelectricity and charged glucose molecules, in hopes of better understanding sugar’s effect on the mechanical properties of the aortic walls.

Another possible application is to treat a condition in which cholesterol molecules stick to the inside of the channel, eventually closing it off.

“We can imagine if we could manipulate the polarity of the artery wall, if we could switch it one way or the other, then we might, for example, better understand the deposition of cholesterol which leads to the thickening and hardening of the artery wall,” Li said.

He cautions that medical applications are still speculations, and require more research.

“A lot of questions remain to be answered, that’s an exciting aspect of the result,” Li said.

Co-authors are Yuanming Liu and Qian Nataly Chen at the UW, and Yanhang Zhang and Ming-Jay Chow at Boston University.

The research was funded by the National Science Foundation, the National Institutes of Health, the Army Research Office, the UW’s Center for Nanotechnology and a NASA Space Technology Research Fellowship.

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For more information, contact Li at 206-543-6226 or jjli@uw.edu.

See also an American Institute of Physics article about the finding and an American Physical Society commentary about the research.

Soon the robots will be flown to campuses across the country, where they will provide the first common research platform to develop the future of surgical robotics.

Members of the public are invited to view the robots at an open house Friday, Jan. 13, from 11 a.m. to 3 p.m. in the UW’s Electrical Engineering Building.

Three of the seven Raven II robots. Each one has a pair of tiny hands that are controlled by a surgeon and can operate on a simulated patient.

Mary Levin, UW Photography

After a round of final tests, five of the systems will be shipped to medical robotics researchers at Harvard University, Johns Hopkins University, the University of Nebraska-Lincoln, the University of California, Berkeley, and the University of California, Los Angeles. The other two systems will remain at the University of California, Santa Cruz, and UW.

“With everyone working on the same, open-source platform we can more easily share new developments and innovations,” said UW electrical engineering professor Blake Hannaford.

While some groups have built their own devices, this slows progress in the field.

“Researchers and funding agencies are tired of one-off robots – they want to pursue projects that use standardized platforms,” Hannaford said. “This is where the field is going.”

The UW group is making its software work with the Robot Operating System, a popular open-source robotics code, so groups can easily connect the Raven to other devices.

The latest version of the Raven has mechanical wrists that hold tiny pincers. Coming soon is a piece that will allow research groups to attach the same tools used by commercial surgical robots.

Mary Levin, UW Photography

The robots were developed by Hannaford and Jacob Rosen, a former UW faculty member who is now an associate professor of computer engineering at UC Santa Cruz.

Until now, most research on surgical robotics in the United States has meant creating new software for commercial robots.

“Academic researchers have had limited access to these proprietary systems,” Rosen said. “We are changing that by providing high-quality hardware developed within academia. Each lab will start with an identical, fully operational system, but they can change the hardware and software and share new developments and algorithms, while retaining intellectual property rights for their own innovations.”

A grant from the National Science Foundation paid for the new devices.

The original Raven robot was completed in 2005 and used for UW research on telerobotic surgery, in which commands are sent over the Internet.

UW electrical engineering doctoral student Hawkeye King holds the circuit boards and connectors for the Raven II robot.

Mary Levin, UW Photography

The latest version, the Raven II, has more compact electronics and dexterous hands that can hold wristed surgical tools, like the newest commercial machines. A surgeon sitting at a screen can look through Raven’s cameras and guide the instruments to perform a task such as suturing. The system, while not approved by the Food and Drug Administration, is precise enough to support research on advanced robotic-surgery techniques.

The new robots were designed and built by Rosen’s group in Santa Cruz. The UW group built the electronics and software; undergraduates helped wire circuit boards, assemble the electronic components and perform tests.

The hope is that the common, open-source platform will allow research groups to share software, replicate experiments and collaborate. Participating schools’ specialties include:

• Harvard mechanical engineers working on “beating-heart” surgery, where a robot compensates for the movement of a beating heart so a surgeon can operate as if on a static surface.

• Johns Hopkins computer scientists working on image analysis, superimposing the surgeon’s field of view on standard medical images.

• UW research on force feedback, using machine intelligence to create barriers around things a surgeon needs to avoid, and attractive force fields around objects the surgeon wants to touch.

All projects are aimed at speeding up procedures, reducing errors and improving patient outcomes.

Four more universities are already in line to get the system. The original Raven robot will move to UW Medicine’s Institute for Simulation and Interprofessional Studies for use by medical researchers there.

"I see huge potential in surgical robotics for incorporating new instruments, more procedures, allowing for remote surgeries, and doing collaborative surgery between multiple surgeons in different locations,” said collaborator Dr. Thomas Lendvay, a UW associate professor of urology and a pediatric urologist at Seattle Children’s Hospital. “Having everyone working on the same, open-source robot will help to make these happen more quickly."

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For more information, contact Hannaford at blake@uw.edu or 206-543-2197, and Rosen at rosen@soe.ucsc.edu or 831-459-5302.

More information is on the group’s blog. Also see the UC Santa Cruz press release.

The Bill and Melinda Gates Foundation also sees potential in the device, adding an additional $611,000 last month  to prior funding for this work. The device could save lives by allowing faster diagnosis and instant treatment for some forms of malnutrition.

While it looks like something you might use to light a barbecue, the Plasma Pencil Atmospheric Mass Spectrometer is really a sophisticated tool that rapidly measures micronutrients – zinc, iron, folate, vitamin A and iodine. The results can then be displayed on a mobile phone or tablet computer within minutes, instead of the 24 hours typically required.

The plasma (purple) touches the blood sample and then a mass spectrometry analysis can reveal five crucial nutrients within minutes and display the results on a mobile device. On the screen each of five nutrients is shown as low or high on a scale where normal values are green.

Mary Levin/University of Washington

Ratner, who led the team that invented this new tool, says the University of Washington is currently pursuing a patent on the PPAMS device.

The plasma pencil creates a thin plume of charged gas – known as a cold plasma – similar in temperature to the neon signs in a bar or theater marquee. When the plasma touches the samples it forces charged particles, or ions, in the sample  to break free of the surface. The spectrometer measures the weight and charge of these ions, and that information pinpoints what is in the sample.

In Bangladesh, where the Gates Foundation is trying to reduce infant mortality and diagnose malnutrition in mothers and babies, a woman might walk 15 miles to see one of the rare medical professionals available. With this device, a health worker could know immediately whether that patient needed iron or folate and could deliver the nutrient treatment on the spot, before the patient leaves.

“This device could be transformative. I’ve been in research for 39 years, and I’m as excited about the significance of this as I’ve ever been,” said Ratner, a professor of bioengineering and chemical engineering. Ratner also holds an endowed chair in technology commercialization.

In the research community, blood samples get this spectrometric analysis all the time –but the machinery might cost $300,000 and be bigger than a refrigerator. Those machines usually require the samples to be carefully prepared by a technician and held under high vacuum.

Ratner and his team combined some recent technological advances into a package that delivers the same data – with this plasma pencil and a tablet computer or cell phone. The key advances are having a plasma pencil at body temperature, having a portable mass spectrometer and applying the right software analysis that allows for an enormous variety of data to be analyzed at one time – instead of analyzing one item at a time.

Giving results in a simple way, by cell phone, means workers with less education can give life-saving treatment accurately in places with few doctors, explained Jeanette Stein, senior researcher who helped design the PPAMS package. Stein holds a doctorate in bioengineering and is working on the analysis software that allows the plasma pencil to provide multiple results simultaneously.

Just as with other devices receiving Gates foundation grants, this one will not be sold for profit in developing nations, but some of its potential uses could bring profits in the developed world.

“Some people use the analogy of the tricorder device from the old Star Trek television show,” Ratner said. Just as those characters pointed their technology toward unknown substances while exploring planets, Ratner imagines wide uses for the wand, including finding contaminants in drinking water, finding lead in plastic toys, or even improving security screenings at airports.

The very first wands may cost about $100,000, but that price should fall with efficient manufacturing, Ratner said. He presented some of his research earlier this year at a meeting of the Biomarkers of Nutrition for Development program, a part of the National Institutes of Health.

For more information, contact Ratner at ratner@uweb.engr.washington.edu

The study finds that military deployment is associated with 1.77 higher odds of physical fighting and 2.14 higher odds of gang membership among adolescent boys in 8^th grade. Girls in 8^th grade with at least one parent in the military were at twice the risk of carrying a weapon.  Study findings were presented October 31 at the American Public Health Association’s annual meeting in Washington, D.C.

“This study raises serious concerns about an under-recognized consequence of war,” said Reed, who has a master’s degree in public health from the UW and now works at the Dana-Farber Cancer Institute in Boston, Mass. “How children cope with their parent’s deployment is a real issue that countless families are confronted with every day.  There is a unique opportunity here to intervene and offer these children – who are acutely vulnerable to negative influences—the support they need so they don’t turn to violence as a way to help cope.”

According to the study, older youth have a higher likelihood of engaging in risky behavior.  In 10^th and 12^th grade, girls with a deployed parent had higher odds of reporting school-based weapon carrying (2.2) and physical fighting (2.6) and being a member of a gang (2.84).  Boys with a deployed parent were at increased risk of school-based weapon carrying (2.87) and physical fighting (2.48), and gang membership (2.08).

Researchers said some youth miss out on the opportunity to learn positive health behaviors while a parent is serving. They cite deployment cycle stress, long and multiple deployments, challenges in accessing support services and emotional distress of the non-deployed parent as possible pathways to missed opportunities.

Reed and team emphasize the urgent need for greater support of innovative school- and community-based initiatives that improve the health and safety of youth in military families. In 2010, almost two million United States children had at least one parent serving in the military. This is a follow-up study that Reed and her team conducted earlier this year that analyzed mental health problems of children with military parents.

This news item was adapted from an American Public Health Association press release.

Jonathan Wright, UW assistant professor of urology, leads the Modawgs team for Movember. Wright is also an affiliate investigator at the Fred Hutchinson Cancer Research Center.

Mary Guiden

Men who participate start Movember 1 with a clean-shaven face.  For the rest of the month, these men, known as Mo Bros, groom, trim and wax their way into the annals of fine moustachery.   Supported by the women in their lives, Mo Bros raise funds by seeking out sponsorship for their Mo-growing efforts.

Jonathan Wright, UW assistant professor of urology and affiliate investigator at the Fred Hutchinson Cancer Research Center, is leading the charge for Movember at UW Medical Center. He said that he wants to not only raise awareness about male cancers, but also wants to help raise the profile of UW urologic oncology.

“With UW Medicine, the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, we have one of the best cancer care programs in the country,” he said.  “I hope that by taking part in Movember, we’ll raise awareness about male cancers and encourage more men to talk with their doctors.”

Janet Stanford, Pete Nelson, Dan Lin and Jonathan Wright lead the charge for Movember.

Mary Guiden

Wright and colleagues study risk factors related to prostate cancer as well as the role of obesity and nutrition in prostate cancer.  Testicular cancer is the most common solid tumor cancer in young men between the ages of 15 and 35, said Wright.  UW physician Daniel Lin, Wright and Janet Stanford, UW research professor of epidemiology based at the Hutch, have also studied male pattern baldness  and prostate cancer risk.   "Movember is a good way for us to showcase the work that we do here, including research and patient care," he said.

Last year, Movember raised over $80 million worldwide to help support the Prostate Cancer Foundation and the LIVESTRONG Lance Armstrong Foundation.  Researchers from UW Medicine and Fred Hutchinson Cancer Research Center receive awards from the Prostate Cancer Foundation to further research efforts.

The UW team, also known as MoDawgs, is seeking additional participants.  Visit the Movember website for more details or contact Wright.

However, several advances are available to assist prospective parents unable to have children on their own. New methods are also at hand to attempt to protect the ability to have babies later on.

“We’re all about family building,” reproductive medicine specialist Dr. Paul W. Zarutskie commented on the UW experts from many fields who work on infertility problems. Zarutskie, acting associate professor of obstetrics and gynecology, directs the newly re-opened University Reproductive Care at UW Medical Center-Roosevelt.

In addition to providing infertility care for all genders, UW  Medicine reproductive endocrinologists also diagnose and treat hormonal issues related to female systems, such as menopausal symptoms, menstrual irregularities, hirsuitism (excessive body hair), polycystic ovary disease, and other conditions.  In some cases, an endocrine disorder is why a woman of childbearing age is having problems becoming pregnant.

Reproductive medicine specialist Dr. Paul Zarutskie conducts a diagnostic ultrasound for patient Tammy Hess. By her side is husband Dr. Bruce Hess.

Clare McLean

Since the closing of the UW in vitro fertilization service in 2005, UW Medicine urologists and obstetrician/gynecologists continued to diagnose and treat infertility, but in vitro fertilization procedures were performed at another lab.

“Now UW Medicine patients have the opportunity of having all such procedures done in-house in a state-of-the art facility,” said Zarutskie. He had obtained his early experience conducting in vitro fertilization at the UW. He trained with leading UW reproductive care experts with a strong national reputation for good pregnancy outcomes.  Seventeen years ago he set up practice in California. When he moved back to the Northwest  to retire, he was asked if he would return instead to the UW as chief of the Division of Reproductive Endocrinology and Infertility.

A major reason why Zarutskie accepted the post, he said, was that UW clinicians and basic scientists are on the verge of scientific developments and practical applications that could change reproductive medicine, provide more options for patients, and protect the viability and health of babies-in-the-making.

As one of many examples, Zarutskie mentioned work by Dr. Randall Moon, whose basic science lab studies cell-to-cell signals that guide embryonic development.  This research is likely to improve the understanding of what promotes optimal growth of a single fertilized egg into a lively baby with all its working parts.  In other physiological research likely to improve reproductive care, Dr. Robert Steiner’s lab looks at nerve transmitters in the brain that regulate the surge of hormones just before ovulation.

On the clinical side, UW urologist Dr. Tom Walsh and male reproduction biologist Dr. Charles Muller in the Male Infertility Laboratory have made major progress in enhancing sperm motility, recovering  sperm with low DNA damage from a sperm sample, and retrieving sperm from testes blocked by structural abnormalities or previous surgeries.

Many UW genomic scientists and anatomists are making discoveries important to pre-implantation screening of fertilized eggs and embryos for genetic and developmental disorders. Maternal/fetal medicine specialist Dr. Edith Cheng is creating new diagnostic and treatment procedures during infertility care and the pregnancies that result.

According to Zarutskie, a good egg is essential to a viable pregnancy.

After age 35, a woman’s ability to establish and sustain a pregnancy drops significantly, with another major drop after age 40. Miscarriage rates are high in middle-age pregnancies.  Pregnancy loss in these instances is often due to genetic changes in older eggs.

“Age in the woman’s body is not so much the factor as is the aging of the egg. As long as you have a healthy egg, a pregnancy is more likely to proceed normally.” Zarutskie said.  He explained that a healthy older woman’s body would likely maintain a normal fertilized egg and a robust embryo.

Dr. Zarutskie goes over his initial findings with Bruce and Tammy Hess.

Clare McLean

When should a couple suspect they are having trouble getting pregnant? Zarutskie said that, on average, a healthy woman who is ovulating regularly and who has a patent uterus and fallopian tubes, and a man who is producing enough active sperm, will usually conceive in six months to a year of unprotected intercourse.  Methods to detect ovulation, such as testing with a urine kit, recording changes in body temperature, or charting the color and consistency of vaginal secretions, can help couples with their timing.

Once a woman is over 35, he said, the clock is ticking and she and her partner should consider making an appointment with their physician after four months without success.  They would then have more time to detect and fix any problems with infertility before the woman enters  menopause and an older man’s sperm production or erectile function declines.

Infertility has a number of causes.  Sometimes only the man or only the woman has an underlying condition, but in 15 to 20 percent of the cases, both partners have contributing factors.

“That’s why couples should realize that the two of them make up the equation,” Zarutskie said.

He listed some of the most common causes of infertility:  ovulation dysfunctions, pelvic infections, endometriosis (in which the lining of the uterus grows on the cervix or other organs), toxin exposure, diet, and such chronic medical conditions as diabetes or thyroid deficiency, and anatomical differences in the uterus or other reproductive structures.  In men, prostate inflammation or infection, anatomical obstructions, and sperm production, including quality and amount, are common factors.

For some younger people – including boys and girls – the issue is protecting their fertility for a future time in their lives when they are established and able to start a family.

Dr. Brenda Houmard, a UW obstetrician/gynecologist, and Dr. Anne Marie Amies, a specialist in pediatric gynecology, are developing a program for young girls with chronic medical conditions, physical disabilities or congenital variations in their reproductive tracts. The program will help transition their medical and surgical care as they move into adulthood and face childbearing concerns.

UW reproductive medicine specialists also see youngsters and young adults just after they are newly diagnosed with a serious condition but before they start medications, radiation or other protocols that could jeopardize their fertility.

Dr. Kathleen Lin, a UW specialist in both male and female infertility, is known for her work in protecting fertility. Many cases are patients about to receive cancer therapy. Among the new technologies are the freezing of eggs or ovarian or testicular tissue.  Physicians also do “crash” retrievals for those about to undergo immediate treatment or surgery that will leave them infertile.

“At present, we can’t guarantee the current methods to gather and preserve the tissues and cells necessary for later pregnancy, but some patients are willing to go ahead the hopes that it might succeed,” Zarutskie said. “Dr. Kathleen Lin and her colleagues provide them with the most promising methods and technology to attempt to achieve their desire to have children later on. In many cases, it is their only chance, if they are having medical treatment that will result in permanent infertility.”

Zaruskie said that this is an exciting, dynamic time for improvements in infertility treatments and fertility preservation.  For instance, while it still happens, the occurrence of quadruplets or quintuplets (or more) from in vitro fertilization is less likely, due to the fact that fewer embryos are implanted in the hopes that at least one will “take.”

Twins and triplets are still a possibility, he said, even when only one embryo is implanted. More than 20 percent of in vitro fertilizations result in twin gestations.  Because multiples increase the chances of pregnancy complications, he said that in vitro fertilization researchers want to understand why and how they happen to reduce the likelihood.

Diagnosis and treatment still cannot give everyone the hoped-for son or daughter. To learn that they cannot have children, despite all efforts to diagnose and treat their infertility, can be devastating to men and women.  Zarutskie said many people take some comfort in learning why they are infertile, move through the pain and come to an acceptance. Some decide to adopt, become foster parents, or love and care for their friends’ or relatives’ children.  Others turn their lives in a different direction that they find fulfilling.

It’s hard to believe that Zarutskie, with his dedication and understanding of what patients go through, and his desire to improve treatments for infertility, found his calling by accident. In high school he planned to become a pilot and an aeronautics engineer who designed missiles. When he was awarded a grant to intern in a lab in Philadelphia, a mistake was made in the paperwork. He was sent to a world leader in sperm physiology.

“I wasn’t disappointed. Instead I was amazed at the science. I switched my interest from rockets to sperm,” he recalled.  As a college student at Duke University he took an introductory psychology course with Dr. Carl Erickson, a noted expert on bird behavior, and was intrigued by how bird hormones get metabolized. In medical school at Hahnemann (now Drexel) he participated in early studies of in vitro fertilization. He learned to apply the heralded findings to patient care, and went on to become a leader in the field of reproductive technology.

“I’m blessed now to be one of the doctors who can now offer tremendous treatment options in reproductive  medicine for patients and  to work among outstanding UW researchers  who are opening  new avenues in fertility, contraception, and infertility research, “ Zarutskie said. “These UW researchers from many disciplines are united by a common bond of excellence and altruism in scientific discovery to benefit others.”

Wessells, Dr. Bill Ellis, Clinic Manager Nancy Eberhardt and Dr. Tom Walsh are leading a quality improvement project to improve patient and staff satisfaction.  The project is known as U-FIT (Urology Flow Improvement Project), a collaborative effort between UW Medical Center, the School of Medicine and UW Physicians.

Bill Ellis, UW professor of urology, talks with lean expert Naomi Maxey about the U-FIT project.

Mary Guiden

The Urology Clinic is already faring well in keeping patients happy and healthy.  In an ongoing hospital initiative, the clinic is the first to have had every patient rate the experience a nine or a 10 (out of 10) on patient satisfaction.  The clinic's ratings have been consistently on the higher side since the rating system started, too.

Urology leaders and staff are working closely on U-FIT with Naomi Maxey, consultant in Performance Improvement/ Lean at UW Medical Center.  Lean is a term typically used in manufacturing, though it’s now spread to the healthcare field.  It refers to eliminating wasteful processes or procedures, or any action, process or product that adds cost without adding any value for the customer.

How does that translate in medicine?  Waste can occur in terms of time, for example.  The project’s goals are to improve patient flow during clinic visits, and to improve daily clinic flow.  Maxey’s work with the department entails developing measures to monitor clinic flow and improving patient, staff and provider satisfaction.

Wessells outlined the AIDET (acknowledge, introduce, duration, explanation and thanks) guidelines as part of the Patients are First and Lean process.  “We need to give the patient time to express all concerns,” he said, while discussing the typical visit.  “Sometimes, a patient’s experience is related to their perception, regardless of how good the care actually was.  If we deliver great care but they think it’s terrible, we’re stuck,” Wessells said.

Ellis said that the number one predictor of patient satisfaction is being seen on time.  He shared a story of his own personal experience with his dentist’s office being efficient, and how his appointment runs smoothly.  “With the growing need for our services, I’m finding it harder and harder to keep up with my schedule,” he said, candidly.

In one activity held in July, patients were armed with clocks and recorded the length of time spent in the waiting room, wait for a doctor and length of the appointment.  Clinic staff and providers took on the role of observer to gain a better understanding of the entire process and how individual roles fit into the process.  It’s a novel approach that was perhaps a little nerve-wracking, but also eye-opening for the urology team, as staff reported back that they really learned from each other.

“We hope to become the shining example of putting our patients first at UW Medicine,” said Walsh.

Caffeine guards against certain skin cancer, according to a new study from the UW.

Klaus Post, Flickr

“This study has been 10 years in the making,” Nghiem explained, “since it is much more difficult to genetically target this protein enzyme specifically. But what it suggests is that caffeine’s protective effect against ultraviolet damage, which we’ve documented in other studies, is likely due to ATR inhibition.”

That means this guarding most likely works at the pre-cancerous stage, Nghiem said, before UV-induced skin cancers fully develop.

“In past studies, we’ve been able to show that caffeine decreases the incidence of skin cancer development,” Nghiem said. “In this study, we set out to determine how that works and how the body protects itself from skin cancer. We were able to show that caffeine manipulates the pathway of this protein in a live mouse by suppressing ATR’s function.”

With more than a million new cases in the United States each year, non-melanoma skin cancer is the most common form of cancer in humans. The researchers suggest that topical application of caffeine could be useful in preventing such cancers, with the added benefit that it directly absorbs UV light, thus acting as a sunscreen.