���� SPRING 2006 VOL. 17, #1 INSIDE Expanding ASD Medical Services ....3 Pediatric Neurogenetics Clinic ...... 4 Thousands of Genes at a Time: Microarray Services ...... 5 New Research Affi liates ...... 8 NEWS FROM THE CENTER ON HUMAN DEVELOPMENT AND DISABILITY AT THE HEALTH SCIENCES CENTER

Preventing Infections, Protecting the Developing Brain

NFECTIONS BEFORE AND Innate immune cells after birth are a major also initiate a cascade of I cause of developmental chemical signals, including disabilities. Take herpes cytokines, needed to activate simplex. In adults, this virus the acquired immune causes cold sores and genital system, which includes herpes, conditions that can be T cells, antibodies, and uncomfortable, but not life other defenses against threatening. However, herpes specifi c pathogens. If the simplex can kill newborns. It acquired immune system can also cause brain lesions has already encountered the that may result in a wide range pathogen in question, an of developmental disabilities, effective response develops depending on which parts of in just a matter of hours the brain are damaged. or days. However, if the Infants are more acquired immune system vulnerable to infection than is encountering a pathogen adults because their immune for the fi rst time, it requires systems are still maturing. “Infants are slower to develop much more time to provide an effective immune response protection: one to two weeks to infection and their response in adults and up to several Illnesses that cause only minor symptoms in adults can lead to developmental weeks in infants. Similar may be less robust,” said disabilities in unborn and newborn children. CHDD researcher Chris Wilson is delays occur in developing Christopher Wilson, M.D., studying ways to protect newborns by boosting their immune systems. research affi liate at the Center acquired immunity in on Human Development and response to vaccines. Disability (CHDD), chair of immunology, on pathogens and are found in cells of Unlike the acquired immune system, and professor of pediatrics. “Newborns the innate immune system, which serve which “learns,” expanding its capabilities also don’t respond as effi ciently to most as the body’s fi rst responder to infection. as it is exposed to new infectious agents vaccines as adults,” said Wilson. When a TLR alerts an innate immune cell and vaccines, the innate immune system Wilson studies the development of to the presence of a pathogen, it triggers a is genetically hard-wired to recognize a the immune system to fi nd ways to protect general attack on all potential pathogens fi xed, limited number of signals mediated very young children from herpes simplex by TLRs. So far researchers have identifi ed and other pathogens. His goal is to identify ten TLRs in humans. For example, one adjuvants, compounds that boost the “Our goal is to . . . improve vaccine TLR detects lipopolysaccharides, large immune system, and use these to make effi cacy early in life.” molecules found only in the membranes of gram-negative bacteria. Other TLRs vaccines more effective in young infants. - Christopher Wilson Specifi cally, Wilson researches how detect structures from viruses, fungi, and the immune response in infants may parasites. Many of the TLRs in humans refl ect reduced or qualitatively different in a matter of hours. The innate immune are very similar to TLRs found in other responses to signals received by Toll-like response can include the redness, swelling, mammals, as well as in birds, reptiles, and receptors (TLRs). TLRs detect structures and fevers associated with infection. insects. See ‘Immune Boost’ on page 2

CHDD OUTLOOK SPRING 2006, VOL. 17, #1 1 CHDD OUTLOOK is published by the Center on Human Immune Boost . . . from pg. 1 Development and Disability (CHDD) at the University of Washington Health Sciences Center. An online version can be downloaded from All infants are born with TLRs. http://www.chdd.washington.edu/gist/outlook.html However, the signaling system initiated by TLRs appears not to be fully functional CHDD is an interdisciplinary center dedicated to the prevention at birth. Some researchers theorize that an and amelioration of developmental disabilities through research, infant’s immune system has to be primed by training, clinical service and community outreach. CHDD includes the University Center of Excellence in Developmental Disabilities and environmental exposures. “The idea is that the Mental Retardation and Developmental Disabilities Research the only difference between the immune Center. systems of infants and adults is that newborns have been living in a sterile environment, and Address correspondence to: then they’re dropped into a dirty world and CHDD OUTLOOK Center on Human Development and Disability it takes a while for things to kick in,” said University of Washington Wilson. Another theory is that the pace of Box 357920 immune system development is genetically Seattle, Washington 98195-7920 determined. [email protected] “Our goal is to try to understand Christopher Wilson http://www.chdd.washington.edu the extent to which these differences are fi xed and immutable, that is hard-wired in Writer, editor, and photographer: Kris Freeman development, or are in fact subject to modifi cation by appropriate environmental Center on Human Development and Disability cues,” said Wilson. These cues could include agonists, compounds that bind to and stimulate TLRs. “The immune system of infants may require different kinds Michael J. Guralnick, Ph.D., Director of signals or more robust signals to achieve immunity than the immune systems Christene James, Administrator of older children,” said Wilson. Wilson’s research program has three primary goals. The fi rst is to determine MENTAL RETARDATION UNIVERSITY CENTER in detail the immune responses of newborns as compared to adults. He and AND DEVELOPMENTAL FOR EXCELLENCE IN colleagues at the UCLA Center for Vaccine Research are studying a group of DISABILITIES RESEARCH DEVELOPMENTAL CENTER (MRDDRC) DISABILITIES (UCEDD) infants by measuring immune function at birth, age seven months, and age sixteen months. Donald F. Farrell, M.D., Adults and Elders Program His second goal is to defi ne the molecular mechanisms responsible for Kathleen Watson, Ph.D., Associate Director, the differences in immune function observed between infants and adults. For Interdisciplinary Research Director example, Wilson and colleagues, including Samuel Miller, M.D., professor of Albert R. La Spada, M.D., Ph.D., Center medicine, of microbiology, and of genome sciences, have identifi ed the structure Associate Director, Geraldine Dawson, Ph.D., Director that allows Pseudomonas aeruginosa to evadeevade detection byby TLR4 in the immune Research Development systems of infants and ill adults. , a common bacterium found in the Center on Infant Mental P. aeruginosa MRDDRC CORE SERVICES Health and Development human intestine, can cause swimmer’s ear and hot tub rash in healthy adults and Kathryn Barnard, Ph.D., Director extremely serious infections in infants, persons with cystic fi brosis, and cancer and Behavioral Science Core burn patients. Wilson also studies the immune response to the bacterium Listeria Susan Spieker, Ph.D., Center for Technology Director and Disability Studies monocytogenes, which can cause severe developmental disabilities. Kurt Johnson, Ph.D., Director Wilson’s third research goal is to identify TLR agonists that might serve as Genetics Core adjuvants, compounds that can boost or trigger the immune system, including the Albert R. La Spada, M.D., Ph.D., Clinical Training Unit activity of vaccines. “Our number one goal is to develop ways to improve vaccine Director John F. McLaughlin, M.D., Director effi cacy early in life,” said Wilson. A hepatitis B vaccine that uses a TLR adjuvant Infant Primate Research was recently approved for use in Europe. Laboratory Community Disability Policy Initiative To test adjuvants for their possible use in human infants, Wilson and his Thomas M. Burbacher, Ph.D., Sharan Brown, J.D., Ed.D., Director colleagues are developing mouse models that respond to TLR agonists the same way Director that humans do. “The TLRs in mice and humans differ in some important ways

Instrument Development Experimental Education Unit and one of these differences affects responses to neonatal pathogens and adjuvants,” Laboratory Richard Neel, Ph.D., Director said Wilson. “So what we’re doing is creating mice that have human receptors Kirk Beach, M.D., Ph.D., rather than mouse receptors.” These animal models will be used to test the ability Director Genetics Program of different adjuvants to improve protection when they are administered together Thomas Bird, M.D., Co-Director Neuroscience Core with vaccines, with the expectation that their responses will more closely predict Kenneth Maravilla, M.D., what would occur in humans. A goal would be “to provide children with immediate protection at the same time they’re developing a protective immune response to the vaccine,” said Wilson. ♦

2 CHDD OUTLOOK Expanding Medical Care for Children with Disorders

some ritualistic behaviors and aggression, can be associated with the underlying pain and stress associated with these medical conditions,” said Geraldine Dawson, Ph.D., director of the Autism Center, CHDD research affi liate, and professor of psychology. Some researchers hypothesize that some episodes of self-injurious behaviors, such as biting or head banging, may cause the body to release beta-endorphins that dampen pain. Or such behaviors may “gate” or serve as a distraction from discomfort caused by medical problems, or may simply be an individual’s way of expressing distress or pain. GI-related issues reported among children with ASD include acid refl ux, constipation, and abdominal pain. Reported sleep disorders are equally In addition to expanding the variety of services available to children with autism spectrum disorders, the varied. “Some children have trouble falling CHDD Autism Center has also increased its capacity by opening a satellite clinic at the UW Tacoma campus. asleep,” said Dawson. “Others might fall Allison Brookes (above, left) directs the new satellite clinic. asleep but waken early or in the middle of the night. There are some children whose sleep cycle is completely reversed so they are literally awake all night long. OW CAN YOU EXPLAIN THAT YOUR emphasis on medical care. As you can imagine, this is not only very stomach aches if you can’t talk? ASD are among the most common disruptive for the family, but a sleep- Or what if you can talk, but developmental disorders in the U.S. These H don’t understand what or where deprived child is not able to optimally neurological disorders disrupt connections benefi t from the educational and other the hurt is? Because of communication in the brain critical to communication, challenges, medical concerns of children resulting in impairments that can range behavioral interventions that we offer.” with autism spectrum disorders (ASD) from an inability to speak, to diffi culties Addressing the medical needs of have often been unrecognized and children with ASD is not intended untreated. In addition, health care to replace the Center’s emphasis on providers have tended to focus on the Because of communication behavioral and educational interventions, behaviors of children with ASD rather than challenges, medical concerns of said Dawson. Instead, the goal is to their possible medical problems. augment those programs by helping To better meet the needs of children children with ASD have often been children become more responsive to them. The Autism Center has established with ASD, the Autism Center at the unrecognized and untreated. Center on Human Development and a monthly clinic focused on medical Disability (CHDD) is expanding its assessment of children with ASD. The clinical services, which have emphasized interpreting facial expressions and other assessment team includes Yemiserach behavioral and educational interventions, problems with non-verbal communication. Kifl e, M.D., medical director of the Sleep to provide a more comprehensive Health issues reported by parents of Disorders Program at Children’s Hospital assessment of medical issues. As part of this children with ASD include sleep diffi culties and Regional Medical Center (CHRMC) effort, the Autism Center has joined the and problems related to gastrointestinal and assistant professor of pediatrics; Dennis Autism Treatment Network, a national (GI) function. Both types of problems Christie, M.D., professor of pediatrics, nonprofi t organization founded in January may affect behavior. “We think that, in head of gastroenterology, and chief of 2005 to develop a uniform “gold standard” some cases, behaviors that we attribute to CHRMC gastroenterology; Felice Orlich, of care for persons with autism, with an autism, such as self-injurious behavior and See ‘ASD Services’ on page 7

CHDD OUTLOOK SPRING 2006, VOL. 17, #1 3 Pediatric Neurogenetics Team: Diagnosing Rare Disorders

AMILIES OF CHILDREN WITH RARE, genetically based neurological F disorders often endure long rounds of medical appointments while seeking a diagnosis. First, get the referral to the neurologist. Next, see the neurologist, who will refer you to a geneticist, who, after ordering tests, will send you back to the neurologist. To streamline the diagnostic process, the Center on Human Development and Disability (CHDD) has established the Pediatric Neurogenetics Clinic, a new consulting service that brings together providers with expertise in neurology, medical genetics, pediatrics, and genetic counseling. “We try to save the family time by having them meet with several specialists at once,” said Mercy Laurino, Ian Glass (left), Katelyn Lawrenz, and Anthony Bouldin discuss Katelyn’s symptoms at the Pediatric M.S., a genetic counselor, and clinic Neurogenetics Clinic. The clinic team is trying to determine if Katelyn’s nerve damage has a genetic cause. coordinator. The new clinic focuses on children, while the existing CHDD Neurogenetics Clinic primarily serves adults. hypothyroidism (a defi ciency of thyroid members may also need time to think hormone) and PKU (phenylketonuria, a over the case, discuss it among themselves, “The diagnostic process for patients genetic disorder in which a child is born and do additional research in the medical with rare neurogenetic disorders can without the ability to break down the literature. Some children may require be so challenging and problematic that amino acid phenylalanine). long-term follow-up, so the team members it requires specialists with expertise in The Pediatric Neurogenetics Clinic, can observe how the disorder unfolds, multiple disciplines,” said Ian Glass, which was formed in November 2005, information that may lead to a diagnosis. M.D., a CHDD research affi liate and currently sees only a small number of In others cases, the disorder may not yet the clinic director. Therefore, during patients. Potential patients are screened. be described or known to doctors. “Again, patient visits, clinic specialists work as a “Even if we determine that an appointment follow-up is important because new reports team to maximize communication and at this clinic wouldn’t be appropriate, we in the scientifi c and medical literature collaboration, said Glass, who is also an hope that we may be able to direct families appear regularly,” said Glass. associate professor of pediatrics and chief of to other services that would meet their If the clinicians are able to reach a the Genetics Clinic at Children’s Hospital needs,” said Laurino. diagnosis, they can provide information and Regional Medical Center (CHRMC). Once an appointment is made, the about the child’s prognosis, for example, Children who are eligible for the clinic clinic’s team of physicians and genetic if the diagnosed disorder is degenerative. may have dysmorphic, or atypical, facial counselors reviews a patient’s personal and They can also determine the mode of features, as well as severe neurological family medical history and help the family inheritance and recurrence risks. The team symptoms, such as mental retardation, make informed choices about genetic members can then direct the family to seizures, movement disorders, unexplained testing. “There are a lot of tests available resources such as peer support groups or muscle weakness, or abnormal brain for genetic disorders and knowing how state-funded resources and special services. scans or muscle biopsies. They may have to apply them well is important because One of the most important benefi ts of a had atypical development from birth or they are potentially expensive,” said Robin diagnosis may be one of the least tangible may have developed typically and then Bennett, M.S., a genetic counselor. “You for families, what Glass calls, “relief from experienced a regression in development. can waste a lot of money if you order them the burden of not knowing.” Other CHDD clinics provide services willy-nilly.” While a diagnosis may provide for persons with several other types of Reaching a diagnosis, if one is families with valuable information, it may genetic disorders, notably inborn errors of possible, may require several appointments. also dash hopes. Cures do not yet exist for metabolism, including severe congenital In addition to analyzing test results, team many of the disorders diagnosed in the

4 CHDD OUTLOOK clinic. “In the meantime, until cures are developed, many valuable managements Thousands of Genes at a Time: and interventions are available for children with neurogenetic disorders to maximize Microarray Core Component Helps their developmental potential,” said Glass. Because understanding the cause of a Design Microarray Experiments disorder is critical to treatment and, more important, prevention, Glass and other clinic specialists are working to isolate Sandra Juul, left, the genes responsible for several types of discusses her inherited neurological disorders. microarray data Glass researches disorders of the with Dick Beyer, cerebellum, the portion of the brain that bioinformaticist controls balance, coordination, and some for the Microarray cognitive functions. For example, he component of the studies Joubert syndrome, a rare autosomal CHDD Genetics recessive disorder with a distinctive Core. Juul’s hindbrain-midbrain malformation. His microarray data group identifi ed the fi rst gene responsible were essential to for this group of disorders. the success of one Thomas Bird, M.D., a CHDD of her recent grant research affi liate and professor of medicine, applications. medical genetics, and neurology, has helped locate genes implicated in Charcot- Marie-Tooth neuropathy type 1B, which causes muscle weakness and other symptoms, and familial Alzheimer’s disease, a rare, early-onset form of the disease that affects people in their forties and fi fties. EN YEARS AGO, ANALYZING A Glass and Bird are regular attending pathways that might be affected by a given single variation in a gene could physicians at the clinic along with Anthony condition,” said La Spada, who is also take up to two days. Now, Bouldin, M.D., clinical instructor of director of the Center for Neurogenetics T with microarray technology, an and Neurotherapeutics and an associate pediatric neurology. Other clinical staff investigator can analyze the expression members include Suman Jayadev, M.D., director of the CHDD. The Microarray of thousands of genes or characterize a neurology fellow, and Sara Michelson, component of the Genetics Core provides thousands of genetic variants in one day. M.S., a genetic counselor. services in collaboration with the Center The team at the Microarray component Several CHDD affi liates were for Ecogenetics and Environmental Health. of the Center on Human Development instrumental in helping to form the Typical experiments might analyze and Disability (CHDD) Genetics Core Pediatric Neurogenetics clinic, including differences in gene activity between cell can help CHDD investigators with all Sidney Gospe, Jr., M.D., Ph.D., professor lines that have been exposed to neurotoxic aspects of microarray experiments, from of neurology and pediatrics; and Phillip experimental design to data analysis. Chance, M.D., professor of neurology Microarray experiments are often used and pediatrics, director of the University for exploratory research and hypothesis of Washington Joubert Center, and chief generation. “Microarray technology of the CHRMC Division of Genetics and allows you to go into a project with very Development. little preconception,” said Al La Spada, To contact the Pediatric M.D., Ph.D., a CHDD research affi liate, Neurogenetics Clinic, call Mercy Laurino associate professor of laboratory medicine, at (206) 598-8771. More information and director of CHDD Genetics Core. about CHDD clinics is available online “A researcher starts with a notion that at http://chdd.washington.edu/families. environmental stress or disease must html#clinics. ♦ A single microarray can collect hundreds of cause a difference in the way genes are thousands of pieces of genetic data. being turned on and off. Microarray research can provide data about the See ‘Microarray’ on page 6

CHDD OUTLOOK SPRING 2006, VOL. 17, #1 5 Microarray . . . from page 5 substances and those that have not, or specifi c area of a particular chromosome, so important service. “When you do this samples from persons with and without now you design a very specifi c SNP array type of high-throughput study, you get a specifi c neurodevelopmental disorder. that only looks at this region,” said Farin. smacked by a tidal wave of data,” said La Data from the microarray experiment can If a microarray with known SNPs doesn’t Spada. The biological signals of interest then provide a basis for more targeted, catch the hypothesized variation, the team are often subtle, and easily overlooked hypothesis-driven experiments. may switch to sequencing arrays in an against a noisy background of signals attempt to discover new SNPs relevant to from thousands of other genes. Teasing Measuring Gene Expression and their research. statistically signifi cant results from such Characterizing the Genome data requires the use of sophisticated Microarrays have typically been used Experimental Design and bioinformatics software. to analyze the activity, or expression, Data Analysis “Fred Farin and Theo Bammler have of genes. Genes code for a protein or a “Before investigators raise their pipette provided excellent service for the design related group of proteins. When a gene is to aliquot an RNA sample, they can meet and completion of microarray experiments, expressed, molecules known as messenger Core members to discuss the best way to and they along with Dick Beyer have been RNA (mRNA) copy the relevant code from design a microarray experiment, including instrumental in data analysis,” said Robert the DNA and carry it to the cell’s protein- issues such as the number of samples Rostomily, M.D., CHDD research affi liate building machinery. The Microarray needed for statistically signifi cant results,” and associate professor of neurological said La Spada. As few as three to four component offers arrays that can detect surgery. Rostomily has used arrays to samples per category may be acceptable. mRNAs or variations in DNA. analyze gene function in brain tumor cell For example, Sandra Juul, M.D., Ph.D., Expression microarrays measure gene lines and compare expression profi les of a CHDD research affi liate and associate expression by detecting the presence and genetically inherited tumors compared professor of pediatrics, used microarrays relative abundance of mRNAs. Arrays are with tumors that arise sporadically. in her research on the hormone available for multiple genomes, including Currently, Beyer is compiling array data erythropoietin (EPO), which stimulates human, mouse, and rat as well as many from public databases to complement other species, such as pigs, dogs, and the body to produce red blood cells. She Rostomily’s and La Spada’s experimental zebrafi sh. is exploring the potential use of EPO to fi ndings. Tiling microarrays cover a complete decrease brain cell death caused by oxygen The Microarray component team also section of a genome, including areas deprivation (hypoxia). Her experiment sees student and resident training as part between genes once referred to as “junk.” required 27 arrays (one for each of three of its mission. Students can be involved These arrays are used to discover or detect groups of experimental animals, three parts in every level of the component’s service, the presence of RNA and other molecules of the brain, and three time points). including experimental design, sample with unknown or regulatory functions. Richard Beyer, Ph.D., Core processing, processing and scanning of SNP (single nucleotide bioinformaticist, and Theo Bammler, microarrays, analysis and visualization polymorphism) microarrays detect Ph.D., bioinformatics coordinator, can of data, and production of posters and variations, or polymorphisms, in DNA also help investigators anticipate how manuscripts. consisting of a change in a single base pair microarray data may be used in follow-up “Working with the Microarray of nucleotides. “SNP microarrays allow us experiments. For example, gene expression component is much more than just to look at polymorphisms in a much more doesn’t always translate into protein dropping off the data and getting the cost-effective, time-effi cient manner than creation because regulatory RNAs, such analysis,” said Farin. “It is a very creative, previous methods,” said Fred Farin, M.D., as “silencing” RNAs, can disable mRNAs. collaborative process.” coordinator of microarray services. Identifying and quantifying the proteins ♦ Sequencing microarrays can sequence that result from gene expression requires up to 600,000 base pairs of DNA at one mass spectrometry and other technologies time. “These newly available arrays can do available through the Proteomics DNA sequencing at a very low cost,” said component of the Genetics Core. Juul has Farin. used services from both Core components Researchers may use several types of in her EPO research. “We did real-time standard or custom arrays in succession. PCR to confi rm key fi ndings from the For example, a team might begin with microarrays and backed that up with a full genome scan of two populations protein data,” said Juul. using a standard, off-the-shelf array. “The Analysis of the data resulting from Fred Farin Al La Spada expression results might point activity to a microarray experiments is an especially

6 CHDD OUTLOOK ASD Services . . . from page 3

are now good who, in turn, mentor younger children guidelines for with ASD by serving as teacher aids at the assessment, CHDD Experimental Education Unit. there still aren’t “You’re teaching the kids how to be a well established contributing member of society, how to guidelines for give back,” said Orlich. treatment, The Autism Center has also increased especially for services by establishing a satellite clinic some of these on the UW campus in Tacoma. “It has underlying allowed us to expand our clinical and medical issues.” training reach down to the South Sound As a result, and Tri-Cities area,” said Orlich. “The new children may clinic has basically doubled our ability to receive different offer diagnostic services.” Allison Brooks, assessments and Ph.D., directs the Tacoma clinic. treatment plans Despite recent increases in capacity, at different the Autism Center is far from meeting the centers, Robin Talley of the CHDD Autism Center works with a client. While expanding its needs of the population of children with depending medical services, the Center continues to focus on behavioral interventions to help ASD in Washington State. In late 2005 on each children with ASD improve their communication and social skills. about 240 families were on waiting lists institutions’s for Center services. Therefore, professional philosophy and training is a critical component of the Ph.D., associate director of the Autism the expertise available there. Center’s work. Recent efforts include Center, a clinical neuropsychologist, and While expanding treatment to partnerships with school districts, to help assistant clinical professor of psychiatry and include medical care, the Autism Center develop their educational and intervention behavioral sciences; Sam Zinner, M.D., a continues to offer all its previously existing programs, and the expansion of web- developmental pediatrician and assistant services, as part of the CHDD’s University based professional training programs for professor of pediatrics; Hower Kwon, Center for Excellence in Developmental health care providers. The Center is also M.D., a child psychiatrist and assistant Disabilities. Coordinated services include fi ne-tuning a social skills curriculum for professor of psychiatry and behavioral diagnosis and intervention for children children with ASD that is scheduled for sciences; and Robert Devney, M.D., a child as young as 18 months. Early diagnosis is release to teachers and clinicians in the and adolescent psychiatrist. Team members crucial because intensive early intervention spring of 2006. The curriculum differs collaborate with , speech and can alleviate many long-term effects of from others currently available by tying language pathologists, and an occupational the disorder, such as delays in cognitive social skills to developmental levels. therapist. and emotional development. The Center’s More information on the Autism In addition to expanding treatment team of early childhood autism consultants Center is available online on the CHDD options for individual children, the uses a variety of research-based techniques web site at http://depts.washington.edu/ Autism Center is working with other to help toddlers improve their play, uwautism/services/index.html. ♦ institutions affi liated with the Autism communication, and social skills. Treatment Network to improve overall The Center also standards of medical care for children with provides a wide variety of ASD. One project is the development services for older children, of a shared database of the results of including diagnosis, ASD treatments and research studies. A behavioral intervention, similar approach—pooling knowledge social skills groups, and among regional research centers—has speech-language and been effective in enhancing care for other occupational therapies. childhood diseases, such as cystic fi brosis New programs include a and childhood leukemia. teen mentoring program in “One of our goals is to try to develop which typically developing more consistent care guidelines for college students mentor Felice Orlich Geraldine Dawson autism,” said Dawson. “Although there adolescents with ASD

CHDD OUTLOOK SPRING 2006, VOL. 17, #1 7 Faculty members appointed as new CHDD research affi liates David Kimelman, Ph.D., is a professor Jaime Olavarria, M.D., Ph.D., is an Jay T. Rubinstein, M.D., Ph.D., is a of biochemistry. Using animal models associate professor of psychology. He professor of otolaryngology–head and (primarily zebrafi sh and frogs) he studies studies the development of organized neck surgery, as well as bioengineering. signaling pathways within and among neural circuits (topographic maps) in the He is also the director of the Virginia cells that are critical to the development visual cortex. He has shown that normal Merrill Bloedel Hearing Research Center. of vertebrate embryos. Results from his map development requires retinal input His primary research focus is to improve research may lead to a better understanding during a well-defi ned critical period. hearing in persons with cochlear implants, of developmental disorders caused by errors His goal is to understand the nature of surgically implanted devices used by in embryonic the retinal persons with development. infl uences severe hearing A major (neural activity impairments. research focus or chemical In particular, is the Wnt cues) that his goal is signaling specify the to improve pathway, topography of perception which is maps, as well of music and of critical as the cellular speech in noisy importance in and molecular environments. a wide array processes that Toward of biological regulate the this end he processes, from the regulation of early timing and duration of this critical period. focuses on embryonic development to the control of He is also interested in studying how the patterns of electronic signals the stem cell growth. His team has determined anomalous factors, such as epilepsy, can implant sends to the brain, with the aim several of the key intracellular interactions affect map development. Olavarria earned of fi nding ways to optimize signals for that regulate this pathway, including the his medical degree at the University of speech and music, while de-emphasizing kinase GSK3 and an inhibitor of this Chile in Santiago, Chile, and his Ph.D. signals for competing sounds. Rubinstein enzyme. Kimelman earned his doctoral in neurobiology at the University of earned his medical degree and a Ph.D. degree at Harvard University. California, Berkeley. in bioengineering from the University of Washington.

Visit the NEW CHDD website at www.chdd.washington.edu

University of Washington Nonprofi t Organization Center on Human Development and Disability U.S. POSTAGE Box 357920 PAID Seattle, WA Seattle, Washington 98195-7920 Permit No. 62