Gelb studies enzymes. These are the minute but busy protein catalysts within our cells that perform a variety of tasks 鈥� such as breaking down food, shuttling away toxins and building up new molecules to keep our cells, organs and bodies in good working order.

But sometimes, due to random genetic mutation, these enzymes struggle to perform their proper roles, causing rare and often fatal diseases in babies and children. Gelb and his colleagues have worked to develop screens that can accurately test in babies how well certain types of enzymes are functioning. Using only a drop of blood, these tests can identify newborns who will need treatment, saving their lives and giving them a robust start.

Ahead of his lecture, Gelb sat down with UW News to discuss his research.

What types of diseases have you been working on to develop newborn screening procedures?

MG: They’re called . The lysosome is a cellular compartment in which enzymes break down large molecules and recycle their components for use by the cell. Each type of lysosomal storage disease is caused by a deficiency in a different lysosomal enzyme. The deficiency disrupts biochemical pathways and cellular metabolism 鈥� eventually leading to disease.

What are the advantages to screening newborns for these rare diseases?

MG: The main advantage is treatment. It is valuable to begin treatment for these diseases early 鈥� before the symptoms of these enzyme deficiencies emerge that would negatively impact development of these children or threaten their lives. This is really the chemistry of saving babies.

How does a tiny drop of blood tell us whether these enzymes are working properly?

MG: These enzymes are present in blood. So we use dried blood spots 鈥� which is something that can be easily collected from a newborn in a hospital or clinic. And we developed a way to use mass spectrometry to screen for how well these different lysosomal storage enzymes are working. Mass spectrometry was a very promising approach because you can easily adapt it to measure the function of many types of enzymes at once in a clinical setting.

What led you to pursue this line of research in the first place?

MG: I first got the idea in the mid-1980s, when my wife was pregnant with our second child and underwent amniocentesis. I asked the nurses what they were checking for, and they said just a few conditions such as Down syndrome. But I had this background in chemistry, and I was studying enzymes. So I thought, “Why not test for enzymes?” I’d also recently seen the film “Lorenzo’s Oil,” which is about a boy with a rare genetic disease. Those experiences planted the idea in my head, though I didn’t immediately pursue newborn screening for enzyme deficiencies.

Then what ultimately led you to develop tests for enzyme functions at birth?

MG: Well, I eventually met here at the UW, who is a professor of pediatrics and an expert in rare genetic diseases. I talked to him about my idea to develop a newborn screen for enzyme deficiencies. He liked it. I then brought in my colleague , a fellow UW professor of chemistry and an expert on mass spectrometry. The three of us form a good team: I’m the chemist, Ron’s the clinician and Frank’s the mass spectrometry expert.

Many lysosomal storage diseases exist. How do you and your colleagues decide which ones to target with your tests?

MG: Well, we want these tests to be informative and useful for families. So, we’ve chosen to focus on diseases for which there are treatments available.

Once you develop an accurate screen for a disease, how could it be incorporated into the standard panel of newborn tests?

MG: In the United States, individual states mandate their own array of tests for newborn babies. There are federal guidelines 鈥� but they are recommendations. It’s ultimately up to the states to decide. So, to get a particular test adopted in your state, there are two basic routes: One is to advocate for the test to be incorporated into the recommended federal guidelines, which are set up through the congressional Newborn Screening Saves Lives Reauthorization Act of 2014. The other route is to simply lobby an individual state government directly. Tests that we’ve developed for two lysosomal storage diseases 鈥� and 鈥� have gone through the federal route. A test for another lysosomal storage disease, , was first adopted by some localities on a state-by-state basis. Through these approval pipelines, newborns are currently screened for dozens of diseases, most of them rare. In Washington state, for example, out of 80,000 babies born this year, screening for one enzyme deficiency may identify four or five babies who need immediate treatment, and about a dozen who need monitoring for possible future disease. But that’s as many as 20 lives saved or improved each year in Washington state, and 20 families spared suffering.

Where would you like to see the field of newborn screening go in the future?

MG: I would like to see every severe genetic disease 鈥� one that causes massive suffering or is life-threatening, but is also treatable 鈥� added to the list. That requires doing the necessary experiments to develop screens for these diseases, and the trials needed to show that those tests are accurate. That way, these screens become a source of hope for families.

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The 42nd annual will be held at 7:30 p.m. Jan. 23 in Kane Hall, room 130.

天美影视传媒 research on children who began life in these institutions shows that early childhood neglect is associated with changes in brain structure. A published this month in shows that children who spent their early years in these institutions have thinner brain tissue in cortical areas that correspond to impulse control and attention.

“These differences suggest a way that the early care environment has dramatic and lasting effects for children’s functioning,” said lead author , a UW assistant professor of psychology.

Since 2000, the has worked to document and treat the children’s health. McLaughlin joined the team about six years ago to focus on brain development.

This study is among the first in any setting to document how social deprivation in early life affects the thickness of the , the thin folded layer of gray matter that forms the outer layer of the brain.

“We find a pervasive pattern of differences [among institutionalized children] in areas of the brain related to attention, working memory and social cognition,” McLaughlin said.

It’s known that children raised in institutions tend to have attention deficit hyperactivity disorder, or ADHD, about four or five times more often than other children, McLaughlin said. The new work suggests how this happens.

The study provides “very strong support” for a link between the early environment and ADHD, McLaughlin said.

Researchers compared brain scans from 58 children who spent at least some time in institutions and 22 non-institutionalized children from nearby communities, all between the ages of 8 and 10. This was the first time in the ongoing study that the children underwent an MRI scan, which creates a 3-D map of the brain.

Related last year found children raised in the orphanages had less gray matter overall, while this study pinpoints the location of those differences. The most significant changes were in areas of the brain related to working memory and attention.

The brain scan images can explain more than 75 percent of the difference in symptoms of ADHD between kids who did and did not spend time in institutions. Thinning was seen in children who left the institution as early as 8 months of age. Researchers also found that the thinner the brain tissue, the more symptoms of inattention and impulsivity the children displayed.

Researchers did not find differences in the volume of sub-cortical structures. No significant difference was seen between girls and boys, who were about equally represented.

When the study began in 2000, some of the young children remained in institutions, while others were adopted by foster families selected and trained by the research team to try to reverse the effects of early neglect. Of the children in the study who spent time in an institution, the new study finds little differences in brain structure between the 31 who remained for a longer time and the 27 who went into high-quality foster care before their third birthday.

“It’s surprising, and a little disappointing,” McLaughlin said. Most characteristics measured by the study were dramatically improved among the children moved to foster care.

“It’s one of the few areas [of behavior] where you don’t see improvements,” McLaughlin said.

The researchers can’t pinpoint exactly which conditions acted to alter brain development. Babies in the institutions had their physical needs met but they lacked socialization, language exposure, human touch and emotional attachment with their caregiver. Future research will try to tease out which stimuli are most important for brain development and at what ages.

ADHD has many different causes and can often be treated, McLaughlin said. This study only looked at the link to childhood deprivation.

The results are meaningful for other countries, such as those in Africa, where orphanages and institutions are becoming more common. The findings may also be relevant for less-extreme situations of neglect.

“Paying attention to very early care environments should be an important public health priority, especially for abandoned or orphaned children,” McLaughlin said.

She will soon participate in a follow-up study in Bucharest. The children, now teenagers around 16 years old, will participate in physical and mental health checkups and can opt to participate in more detailed tests such as the brain scans.

The three researchers who lead the Bucharest early intervention study 鈥� at Harvard Medical School, at the University of Maryland and at Tulane University 鈥� are co-authors on the paper. Other co-authors are and Warren Winter at Harvard Medical School.

The research was funded by the John D. and Catherine T. MacArthur Foundation and the National Institutes of Health.

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聽For more information, contact McLaughlin at mclaughk@uw.edu or 206-616-7863.

According to information issued by the National Institutes of Health, 鈥淭he National Science and Technology Council was commissioned by President Clinton in 1996 to recreate the award program to honor and support the extraordinary achievements of the finest scientists and engineers, who, while early in their research careers, show exceptional potential for leadership at the frontiers of scientific knowledge鈥� The Presidential Award is considered to be one of the highest honors bestowed on scientists and engineering beginning their independent careers.鈥�

Clark was recognized for his studies on the neurobiology of motivated behavior. He conducts such research to explore important public health concerns. His Presidential Early Career Award will support his investigations of the neural mechanisms of risk preference following adolescent alcohol use.

People often have their first experiences drinking alcohol as teenagers, and some do so during binges. Clark鈥檚 research project summary notes that these episodes can sometimes be the start of problem drinking, and have been associated with impaired decision-making. He also noted that studies in animal models of teen drinking suggest that alcohol exposure during this time of life can produce long-term difficulties in assessing risk when making choices.

鈥淎dolescence is a critical period of maturation,鈥� Clark wrote, 鈥渨here brain development may be disrupted by alcohol use.鈥� Clark plans to test several hypotheses on how teenage drinking might influence risk preference. Specifically, he added, chronic alcohol exposure during adolescence might alter the mesolimbic dopamine system, which has been linked to reward processing.

鈥淎n early age of onset of alcohol use appears to be linked to a vulnerability to drug abuse problems in adulthood,鈥� Clark said. 鈥淲e would like to understand how exposure in the teen years might lead to chronic alcoholism in adults.鈥�

Clark earned a Ph.D. in psychology in 2006 from the UW, and the next year took a position as a postdoctoral fellow with Paul Phillips in the UW Department of Psychiatry and Behavioral Sciences. Now on the UW medical school faculty, he is part of the Center for Drug Addiction Research.

He is the 11^th faculty member at UW Medicine to receive a Presidential Early Career Award for Scientists and Engineers since the program started.

The device and research using it to study the brain patterns of children will be presented June 18 at the meeting in Seattle. A , developed by the UW’s , was , an online open-access journal.

“Scientists needed a tool that allows them to see in real time what a person is writing while the scanning is going on in the brain,” said , director of the center’s Instrument Development Laboratory. “We knew that fiber optics were an appropriate tool. The question was, how can you use a fiber-optic device to track handwriting?”

To create the system, Lewis and fellow engineers Frederick Reitz and Kelvin Wu hollowed out a ballpoint pen and inserted two optical fibers that connect to a light-tight box in an adjacent control room where the pen’s movement is recorded. They also created a simple wooden square pad to hold a piece of paper printed with continuously varying color gradients. The custom pen and pad allow researchers to record handwriting during functional magnetic resonance imaging, or fMRI, to assess behavior and brain function at the same time.

Other researchers have developed fMRI-compatible writing devices, but “I think it does something similar for a tenth of the cost,” Reitz said of the UW system. By using supplies already found in most labs (such as a computer), the rest of the supplies 鈥� pen, fiber optics, wooden pad and printed paper 鈥� cost less than $100.The device connects to a computer with software that records every aspect of the handwriting, from stroke order to speed, hesitations and liftoffs. Understanding how these physical patterns correlate with a child’s brain patterns can help scientists understand the neural connections involved.

Researchers studied 11- and 14-year-olds with either dyslexia or dysgraphia, a handwriting and letter-processing disorder, as well as children without learning disabilities. Subjects looked at printed directions on a screen while their heads were inside the fMRI scanner. The pen and pad were on a foam pad on their laps.

Subjects were given four-minute blocks of reading and writing tasks. Then they were asked to simply think about writing an essay (they later wrote the essay when not using the fMRI). Just thinking about writing caused many of the same brain responses as actual writing would.

“If you picture yourself writing a letter, there’s a part of the brain that lights up as if you’re writing the letter,” said , professor of radiology and principal investigator of the UW . “When you imagine yourself writing, it’s almost as if you’re actually writing, minus the motion problems.”

Richards and his staff are just starting to analyze the data they’ve collected from about three dozen subjects, but they have already found some surprising results.

“There are certain centers and neural pathways that we didn’t necessarily expect” to be activated, Richards said. “There are language pathways that are very well known. Then there are other motor pathways that allow you to move your hands. But how it all connects to the hand and motion is still being understood.”

Besides learning disorders, the inexpensive pen and pad also could help researchers study diseases in adults, especially conditions that cause motor control problems, such as stroke, multiple sclerosis and Parkinson’s disease.

“There are several diseases where you cannot move your hand in a smooth way or you’re completely paralyzed,” Richards said. “The beauty is it’s all getting recorded with every stroke, and this device would help us to study these neurological diseases.”

The work was supported by a grant from the National Institutes of Health. Other UW collaborators on the project are Peter Boord, Mary Askren and Virginia Berninger.

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For more information, contact Reitz at freitz@uw.edu, or 206-543-9023.

The research team analyzed responses collected in a 2010 Washington state survey of more than 24,000 public school students in grades eight through 12. The study found that 14 percent, 11 percent and 9 percent of male students in grades 8, 10, and 12 respectively reported being bullied because of perceived sexual orientation. For female students in those grades, the numbers were 11 percent, 10 percent and 6 percent respectively.

鈥淭hese findings underscore the need for early prevention efforts before 10^th grade,鈥� wrote the authors.

Being bullied because of perceived sexual orientation was linked to lower quality of life scores and increased the odds of depressed mood or consideration of suicide. Moreover, the size of these associations was greater than being bullied for other reasons

鈥漎outh at this age group are extremely vulnerable to the effects of bullying when they are perceived rightly or wrongly to be gay, lesbian or bisexual. The effects are profound for many youth struggling with issues of identity and self-esteem,鈥� said Patrick, principal investigator of the study.

鈥淏ully-prevention or harm-reduction programs must address bullying because of perceived sexual orientation. All youths are entitled to safe school environments and support is essential for those who are most vulnerable to being bullied because of perceived sexual orientation,鈥� the study concluded.

Read the in the American Journal of Public Health.

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