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reSearch Magazine Issue 1
 
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This biannual publication, reSearch, is dedicated to the mission of informing and inspiring readers by highlighting scientific performance at The Research Institute at Nationwide Children's Hospital.

This biannual publication, reSearch, is dedicated to the mission of informing and inspiring readers by highlighting scientific performance at The Research Institute at Nationwide Children's Hospital.

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    reSearch Magazine Issue 1 reSearch Magazine Issue 1 Document Transcript

    • listening to the heart’s smallest messenger How this device gets cells to tell research A PublicAtion of The ReseaRch InsTITuTe aT naTIonwIde chIldRen’s hospITal
    • research is dedicated to the mission of informing and inspiring readers by highlighting scientific table of contents a message from the president performance at the Research institute at nationwide children’s Hospital. this publication is produced biannually by the Marketing and Public Relations Department at nationwide children’s Hospital. Dear Friends and Colleagues: One of the prevailing joys of being a scientist is the knowledge that each day could fe at ure s be a day of fascination and revelation. The intellectual pursuit of a life-altering 4 wanted: a Generation of Quitters discovery, particularly one that could improve the life of a child, drives us to brady Reynolds, PhD, has never smoked a cigarette in his life. continue our years of research. Yet most of his day is spent trying to find ways to quit. Our excitement and fascination shouldn’t stay within our walls. We want to share le a deRs hIp 8 The Importance of studying adolescents these experiences with you. So welcome to our first issue of reSearch. The Research Institute at What if in addition to the normal awkwardness of adolescence, nationwide children’s hospital you are diagnosed with an illness that will last a lifetime? findings Within these pages, you will discover how impulsive thought processes affect a teen’s John a. Barnard, Md suggest that adolescents shouldn’t be treated like adults, but they President ability to quit smoking; be privy to the way heart cells “communicate” and what they shouldn’t be treated like children either. lauren o. Bakaletz, phd say about heart disease; and be revealed to the world of an adolescent facing a chronic Vice President, Basic Sciences Research Kelly Kelleher, Md, Mph 12 listening to the heart GI illness, and how we are searching for the ideal ways to treat this condition. Vice President, Health Services Research Down at the cellular level lives the cardiac myocyte, the heart’s smallest messenger. Although it is simply a microscopic cell extracted Join us in our enthusiasm for the future of pediatric research and in the milestones Grant Morrow III, Md Medical Director from the heart muscle, it has a story to tell. that is, if you’re listening. – sometimes incremental and sometimes monumental – we reach each day in our daniel R. Mann pursuit of discovery. Vice President, Research Administration and Operations e xt ras Katherine s. Milem Vice President, Research Business Services 7 noteworthy news about the Research institute and its faculty. research Writer and editor 16 Into the Future John Barnard, Md Melissa hamilton President the look of Research in 2012. the Research institute at nationwide children’s Hospital Designer Tanya Bender Professor of Pediatrics Photographers o n tHe co v eR the ohio State university college of Medicine Brad smith dan smith Loren E. Wold, PhD, examines a device used to study the function of heart muscle cells, a tool that could change the way science understands heart disease. Manager, Research communications Jan arthur contact us at ResearchMagazine@nationwidechildrens.org research | 3
    • to complete the eDt, the participant views a computer screen that displays two monetary amounts, one that offers a smaller immediate reward and another that offers the possibility of a larger reward at a delayed time. for example, do you want 15 cents now or the possibility of 30 cents 28 seconds from now? if the participant clicks the Wanted: computer to choose 15 cents now, coins come clinking out of a specialized change machine that is connected to Brady Reynolds, PhD, demonstrates the computer. the Experiential Discounting Task. “that’s why it’s called the experiential a Generation of Quitters Discounting task. Participants actually experience the choice they make at that moment,” said Dr. Reynolds. the program at nationwide children’s in January of 2006, one of the first- and-only smoking cessation programs these findings have implications for designing effective smoking cessation programs. “A person who discounts HoW ReSeARcH iS finDing neW WAYS to HelP ADoleScentS Quit SMoking for adolescents in central ohio. most by delay is someone whose B if the participant instead chooses 30 behavior is led by more immediate rady Reynolds, phd, has to smoke into adulthood, practically a larger reward that is delayed for a cents, they have to wait a set period of Adolescents who enroll in this pro- consequences. to reach an adoles- never smoked a cigarette guaranteeing increased health risks, period of time. Delay discounting has time to see if they will actually receive gram attend a smoking cessation cent smoker who discounts a great in his life. Yet most of his since approximately half of people been shown to play an important role the money, since the delayed option class held at nationwide children’s deal, you need to make the benefits day is spent trying to find who smoke are expected to die from in cigarette smoking behavior. may not actually pay out each time. main campus once a week for 10 of quitting smoking more immediate. ways to quit. smoking-related illnesses, according this time delay can vary from zero weeks. During the first half of the Programs that stress the long-term to further understand this relation- seconds, 7 seconds, 14 seconds, to program, participants are taught to the World Health organization. effects of smoking are going to be less You won’t see him crunching on a ship, Dr. Reynolds has developed a 28 seconds. After the time delay, the health and smoking education effective for these piece of nicotine gum or slapping on Although adolescent smokers often delay discounting task that he believes selected money adolescents,” said nicotine patches. instead, you’ll find continue their habit into adulthood, overcomes some of the shortcomings amount appears “That’s why it’s called the experiential discounting Dr. Reynolds. him crunching numbers and trying it may not always be clearly by of previously developed methods. in the computer’s to patch holes in research about what choice. Sixty-one percent of adoles- “bank account” Task. participants actually experience the choice Although Dr. Most delay discounting tasks ask motivates adolescents to quit smoking. cents report wanting to quit smoking participants to choose between that will be cashed they make at that moment,” said dr. Reynolds. Reynolds is quick cigarettes and 59 percent report a out once the par- to suggest his that’s because as a principal investi- hypothetical situations, such as, quit attempt in the past year. ticipant has completed the entire task. including the common myths of findings could be applied to current gator in the center for biobehavioral would you prefer $10 now or $100 smoking. class five is the required smoking cessation programs, he says Health at the Research institute at So why can’t they just quit? that’s one year from now. but according to every time the participant chooses “smoking quit date” for participants that even the best of research needs to nationwide children’s Hospital Dr. what Dr. Reynolds wants to find out. Dr. Reynolds, this hypothetical method the smaller, immediate amount, that and the remaining sessions are used be strengthened by further evidence. Reynolds is using research techniques can be tricky for adolescents. quantity goes down for the next choice As a behavioral psychologist, Dr. as a support group to help deal with that’s why he has made the eDt to learn how to help adolescents (the next option may give you 10 Reynolds has spent his career trying “because adolescents, particularly withdrawal and lifestyle changes available via the web for behavioral become quitters. cents). this calculation helps provide a to understand what motivates people younger adolescents, aren’t as psycho- associated with quitting smoking. laboratories throughout the world. clearer measure of delay discounting. other investigators can access the “Adolescence is a sensitive period to to certain behaviors. Although some logically developed in many ways as those who chose the smaller, immedi- Participants of the n-o-t program at begin smoking,” said Dr. Reynolds. motivators tied to cigarette smoking adults; they perceive information differ- software, purchase the appropriate ate reward more often than the larger, nationwide children’s Hospital can have already been identified, such as ently,” said Dr. Reynolds. “for example, coin machine and conduct their own According to surveillance by the delayed option are described as being choose whether or not they want to impulsivity, there is still a lot to learn. they don’t seem to understand the con- experiential delay discounting studies. Morbidity and Mortality Weekly Report, more impulsive discounters. perform the delay discounting task cept of time (like a year) as adults do.” Dr. Reynolds will then analyze their approximately 2,000 adolescents “impulsivity is not described by one along with their participation in the to determine how delay discounting findings from the eDt, in hopes that initiate smoking each day. that means type of behavior. it is multifaceted,” that’s why Dr. Reynolds developed 10-week program. Dr. Reynolds’ delay relates to cigarette smoking behavior, they can also help shape smoking that every minute, an adolescent is said Dr. Reynolds. the experiential Discounting task discounting studies with this adolescent the eDt is being evaluated with an cessation and education programs trying a cigarette for the first time. (eDt), a computer-based program smoking population have shown that A recently studied aspect of impulsivity adolescent smoking cessation program for adolescents. that measures delay discounting by the adolescents who discount more And that first time may not be the is delay discounting. Delay discount- called not-on-tobacco (n-o-t), the often are those who are less likely to More Smoke Signals requiring participants to choose last. Studies show that the majority of ing describes an individual’s preference official teen smoking cessation quit smoking, even after participating the eDt is not the only method between moment-in-time situations as adolescents who smoke daily continue for a smaller, immediate reward over program of the American lung in the n-o-t program. Dr. Reynolds is using to understand opposed to hypothetical situations. Association. Dr. Reynolds initiated 4 | research research | 5
    • Circulatory System Could Provide New Strategy for Mus- cular Dystrophy Gene Therapy Future Study to Monitor Medication Usage and Effects Technique Helps Diagnose Asthma Attacks Circulatory System Could Provide New Strategy for Muscular Dystrophy Gene Therapy Future Study to Monitor Medication Usage and Effects Tech- nique noteworthy | Helps Diagnose Asthma Attacks Circulatory Sys- tHe ReSeARcH inStitute At nAtionWiDe cHilDRen’S HoSPitAl Circulatory System Could Provide the system alerts a trained psychiatric nurse to contact the New Strategy for Muscular Dystrophy patient or parent and when necessary, contact the patient’s Gene Therapy physician or hospital emergency services. preliminary results have shown that the participants Although Dr. Reynolds would like to investigators at the Research institute have delve into these new areas of research, the PhaSt project could provide medication monitoring in significantly maintained abstinence from smoking received an $8.1 million grant from the he is not abandoning the eDt. in fact, instances when families or the overstretched child mental national institutes of Health to learn more when they were being paid, even during a period at fellow principal investigators at the about strategies to treat muscular dystrophy, potentially health systems do not have the resources to follow the Research institute have plans to use it recommended–often weekly–physician visits. the end of the program when it didn’t matter how leading to two new gene therapy approaches. the primary to determine the role delay discounting research strategy will use the circulatory system for gene much they smoked. plays in behaviors beyond smoking delivery of the dystrophin gene, as opposed to direct the study is expected to begin in early 2008 and continue through 2010. initial funding for the study was made cessation. Planned studies include injections into individual muscles. this vascular delivery smoking behavior. Working with program style would encourage possible by a collaborative grant between nationwide measuring suicidal impulsivity and strategy provides a more favorable opportunity for collaborators, he is collecting data from maintenance by providing the needed children’s and the ohio State university. studying what makes people likely to correction of lost function throughout the body reaching a web-based contingency management peer support group,” said Dr. Reynolds. use safety equipment, such as sports many muscles, as well as the heart. Study Helps Differentiate Between program. Participants of this program safety equipment or parent use of infant until then, the n-o-t program Asthma and Vocal Chord Dysfunction are asked to record “video diaries” of car seats and home smoke alarms. Two Centers of Emphasis Obtain continues to make an impact. of the Doctors at nationwide children’s Hospital themselves three times a day using web Leadership more than 60 adolescents who have performed a clinical study using spirometry cameras. At the time of each “diary even though Dr. Reynolds’ original Bill smoyer, Md, Robert c. kelsch chair participated in the n-o-t program at in the emergency Department to identify entry” they blow into a picometer, a plans for the eDt were focused on of Pediatric nephrology at the university nationwide children’s, 25 percent adolescents who had findings suggestive device used to measure carbon adolescents, his findings may have of Michigan, has been appointed director made a significant decrease in smoking of vocal chord dysfunction (vcD) compared to an acute monoxide levels, a distinct marker implications for adult smokers. “the of the center for clinical and translational frequency and many of the others asthma attack. the manuscript was published in the July of how much tobacco someone has research would have to be explored, but Research at the Research institute. Dr. Smoyer will work report at least some decrease. issue of Pediatric Pulmonology. smoked in the past three to six hours. there are indications that these findings to orchestrate further development of clinical and Participants are given money for Genetic Contributions may apply to the adult population since translational research across the organization. According to the study, 12 of the 17 adolescents who continued abstinence during the beyond his current research methods, research has already shown that adult presented to the emergency Department with difficulty treatment phases. Dr. Reynolds would like to further the smokers discount more than adult After serving in an interim position, breathing, but with high normal oxygen levels, were understanding of adolescent smoking non-smokers,” he said. leif nelin, Md, has been appointed found to have evidence of vcD on spirometry. this led Preliminary results have shown that the director of the center for Perinatal cessation by investigating how genetics to a change in the therapy for these patients. Spirometry participants significantly maintained for now, however, Dr. Reynolds plans Research at the Research institute. contribute to smoking habits. He and used in the acute setting of difficulty breathing can help abstinence from smoking when they to focus his research on ways to help Dr. nelin plans to continue to improve chris bartlett, PhD, principal investiga- differentiate vcD from asthma attacks. were being paid, even during a period adolescents specifically. “if we can the integration between the center for tor in the center for Quantitative and change smoking habits during at the end of the program when it Perinatal Research and the Division of neonatology, the study suggests that if more emergency departments computational biology at the Research adolescence, we’ll be able to greatly didn’t matter how much they smoked. an ability he demonstrated during his interim position. made use of the spirometry test, it could cut down on the institute, are already collecting pilot data reduce the long-term effects of number of children who are misdiagnosed and potentially With continued funding, Dr. Reynolds that involves isolating genes associated smoking,” said Dr. Reynolds. Future Study to Monitor Medication hospitalized. hopes to maintain this method of with different neural systems in the Usage and Effects research with the hopes of one day brain (many of which are associated For more information about the A research study is planned to trial a combining the contingency manage- with addiction) to search for genetic not-on-Tobacco program at new technology that helps monitor how ment model with the n-o-t program markers of delay discounting. nationwide children’s hospital, medications, specifically anti-depressants, model, for a more comprehensive call (614) 355-3445, or click on are used in children and teens. other hopeful genetic studies include “education classes” at smoking cessation course. investigating recent research in the field nationwidechildrens.org. the project, named “PhaSt”, or Pharmaceutical Safety “by reinforcing positive behavior, that suggests the relationship between tracking: Managing Medications for Patient Safety, involves Learn about more research the contingency management portion smoking behavior in parents and their Further Reading: Reynolds, b.; Patak, M.; Shroff, an interactive voice response telephone system to contact news and highlights at could help kids get through the children can most likely be accounted P. “Adolescent smokers rate delayed rewards as less parents or teenage patients. the system requires simple yes withdrawal stage that is common for by their genetic relatedness, not just certain than adolescent nonsmokers.” Drug and Alcohol Dependence, v. 90 issue 2-3, 2007, p. 301-3. or no answers to questions about the medications and their NationwideChildrens.org/research. with the early days of smoking by a child mimicking parental behavior. side effects. When a parent or patient indicates a problem, cessation. then combining the n-o-t 6 | research research | 7
    • “IBD is an ideal disease for investigating adolescent adjustment to chronic illness, given its adolescent onset, and embarrassing, socially limiting, and appearance-changing symptoms.” children’s Hospital, are studying adolescents to better research on adolescent adjustment to other conditions, understand how this patient population adjusts to either,” said Dr. Mackner. chronic illness. overall, a comprehensive adolescent perspective is lacking. Although their research might not be poetic, what their “the research on psychosocial adjustment to pediatric findings suggest seems to be worth writing home about: chronic illness has focused primarily on children. if adoles- adolescents shouldn’t be treated like adults, but they cents are included in this research, they are often included shouldn’t be treated like children either. in the same sample with younger children. even when adolescents are the focus, development issues are often The Uniqueness of Adolescence not taken into account,” said Dr. Mackner. Adolescence involves more changes than any developmental period other than infancy. When Drs. Mackner and crandall refer to adolescents, they mean those age 11 through 18, since this is the period these years are wrought with extreme biological changes when most changes in psychosocial adjustment appear. including raging hormones, acne, and increased body So, why should an 11-year-old be categorized separately odor and body hair. from an 8-year-old? When it comes to psychosocial on top of the stressors normally associated with adoles- development, adolescence and childhood are worlds cence, imagine having an incurable condition in which apart. Adolescents spend significantly more time with your main symptoms include diarrhea, rectal bleeding, their peers than children do. close friends begin to abdominal pain and delayed puberty. surpass parents as a primary source of social support and Wallace Crandall, MD and Laura Mackner, PhD acceptance by peers plays an important part of adolescent inflammatory bowel diseases (ibDs) such as crohn’s self-identity. involvement in extracurricular activities disease and ulcerative colitis are chronic conditions in contributes not only to acceptance by peers, but also The Importance of which inflammation in the intestines can result in these takes on an important role for those planning to apply sometimes embarrassing symptoms. Although ibD has to college. in addition, the development of romantic typically been viewed in the medical community as an relationships becomes a significant focus. Studying Adolescents adult disease, about 25 percent of ibD cases occur in the pediatric population, with the majority beginning their onset in adolescence. Adjusting to the normal changes adolescence brings is tough enough; adolescents with When Illness Adds Insult to Injury With so many aspects of psychosocial development how do you study whether or not an adolescent is adjusting well to this new stage of life? Researchers work to understand chronic ibD are given even more to adjust to. Illness in a neglected Field of study “ibD is an ideal disease for investigating adolescent “there are two main aspects of studying psychosocial adjustment to chronic illness, given its adolescent onset, functioning,” said Dr. Mackner. “one is psychological A and embarrassing, socially limiting, and appearance- functioning: Are they depressed? Do they have anxiety? poet once remarked, “You don’t have to suffer to be a poet. Adolescence is enough changing symptoms,” said Dr. Mackner. Do they have other types of behavioral problems? the suffering for anyone.” but what if in addition to the normal awkwardness of other is social functioning: How are they getting along adolescence, you are diagnosed with an illness that actually will last a lifetime? So how has research into this condition shed light on with friends? Do they have friends? Are they able to laura Mackner, phd, an investigator in the center for biobehavioral Health at the how adolescents adjust to chronic illness? therein we participate in social activities at an age appropriate level? Research institute at nationwide children’s Hospital, and wallace crandall, Md, Director find the issue. Are they able to attend school and do well?” of the center for Pediatric and Adolescent inflammatory bowel Disease at nationwide “When we first started investigating this area of research Drs. Mackner and crandall studied the psychological about five years ago, there was little research focusing on and social aspects of adolescents with ibD in order to the psychosocial aspects of ibD. there hasn’t been much 8 | research research | 9
    • understand whether people sooner, like psycholo- the inflammation of the intestine,” said Dr. crandall. be used to help identify risk factors, especially during having the condition might gists and social workers to try “better control of stress could help with the psycho- the first year of diagnosis, when the majority of disease affect psychosocial func- to help patients with that ad- social aspect, but could potentially help with disease adjustment is expected to occur. tioning. What they found justment process as opposed control issues as well.” • The role of social functioning: Although preliminary was that adolescents with to waiting until there is some Drs. crandall and Mackner would utilize behavioral results show that ibD has an adverse impact on ibD have significantly fewer crisis,” said Dr. crandall. measures to study patient stress levels, as well as adolescent social functioning, more research needs to close friends than healthy identifying risk factors could markers of inflammation at the bowel level to see be done to clearly identify the extent of disease impact. adolescents and participate also help identify appropriate if stressors predict flares in disease. Dr. Mackner identifies this as a vital need considering in fewer organized activi- treatment methods, such as social functioning is so important during adolescence. ties. these results suggest Dr. crandall would also like to investigate the genetic emphasizing coping strate- “Adolescents’ social lives are very complex and we don’t that ibD has an adverse components of stress as it relates to ibD. there are gies during therapy or group yet know how ibD affects them or how to best help impact on adolescent social normal variations within a gene known as polymor- intervention situations. adolescents in this area,” said Dr. Mackner. functioning. this finding is phisms that result in different effects. these gene important because research So Much More to Learn variations may influence the effect of stress on ibD. • The role of medication: “one of the medications used has shown social function- More studies need to be to treat ibD is steroids and steroids have been associated ing among children is an • The role of depression: “there is research that exists with depression and emotional liability,” said Dr. Mackner. completed before the re- important predictor of that shows that children with ibD have higher rates of “they also are associated with aspects of adolescence search field is robust enough difficulties later in life. depression than healthy kids,” said Dr. Mackner. “in the that can be additionally stressful like weight gain and to start drawing conclusions past, we always thought that it was a reaction to having increased acne.” about adolescent adjustment Drs. Mackner and crandall this disease since it is a disease that is often embarrassing to chronic illness, especially believe that these differ- to have.” However, new evidence suggests that there • The role of age at disease onset: “A lot of the chronic adolescent adjustment in ibD. ences in social functioning may be aspects of the inflammatory process that health conditions that have been studied from the may be attributed to the “there are very few actually contribute to the development of depression. psychosocial research are ones that children are born fact that ibD is more of researchers who focus on a stigmatized disease. “A psychosocial issues in pedi- lot of diseases, for lack of atric ibD,” said Dr. Mackner, “If there is a way to know up front who is going to have difficulties better words, are socially who believes there are only down the line, we could involve the appropriate people sooner…” acceptable,” said Dr. a few researchers in the crandall. “everybody “Kids with IBD have a stigmatizing nation doing so. understands asthma, disease. They don’t want to talk about future studies would involve looking specifically at the with or acquire early in life,” said Dr. Mackner. “coping everybody understands With continued funding, the symptoms because they can be Drs. crandall and Mackner role of pro-inflammatory cytokines in ibD. these proteins mechanisms involved in this situation are vastly different cancer. if a kid with asthma that are released by white blood cells have been found to compared to being 13 and suddenly being diagnosed or cancer goes to school, very embarrassing. It is a condition want not only to tackle the be byproducts of both inflammation and depression. with a chronic gastrointestinal disorder.” future research kids rally around them; that can be quite isolating.” unanswered questions that would investigate how age at disease onset affects they don’t think they’re their previous research has “there is a substance known as tumor necrosis factor psychosocial functioning in adolescence. going to catch it. kids with raised, but also focus on the alpha that is known to be an important contributor to ibD have a stigmatizing bi-directional nature of ibD, the inflammatory process in crohn’s disease,” said Dr. even though Drs. Mackner and crandall have earmarked disease. they don’t want to the relationship between crandall. “Another one of its effects is causing a poor these as areas that need further research, they probably talk about the symptoms because they can be very mind and body. appetite. So if a patient comes in and says ‘i’m tired; won’t stop there. “Just being in the clinic and interacting embarrassing. it is a condition that can be quite isolating.” i’ve been having trouble sleeping; i don’t want to eat,’ with ibD patients helps spark new research ideas,” said “Disease affects psychosocial factors and psychosocial factors are they depressed or is it a symptom of the crohn’s Dr. Mackner. Although they have identified the fact that social functioning affect disease,” said Dr. crandall. “When you’re treating one disease?” Questions like these are of special importance may be impaired in patients with this condition, that’s just of these things, you’re potentially treating both sides of the What a good problem to have. More data would bring to an adolescent population since Drs. Mackner and half the battle. “the extent of the difficulties is unknown,” equation. We need to continue research to tease out how the health care field a little closer to providing new crandall think that kids with ibD who are more said Dr. Mackner. much of it is a psychological effect and how much of it is a answers to the question that Dr. crandall says is of depressed are going to have more problems with disease effect.” utmost importance. social functioning. learning more about the extent of the difficulties may help identify risk factors for this patient population. “once To do so, they’d like to focus research on the • The role of the adjustment process: Drs. crandall and “How do adolescents adjust to chronic illness? the we identify risk factors, we’ll be able to identify which following role players: Mackner would like to develop a web-based program in answer is we don’t know, but we need to find out.” adolescents are likely to have problems in adjustment,” • The role of stress: “there is some thought that stress which adolescents with ibD would fill out questionnaires may affect the disease activity, rather than just the way Further Reading: Mackner, lM.; crandall, Wv. “Psychological factors said Dr. Mackner. quarterly regarding stress, coping skills, social support affecting pediatric inflammatory bowel disease.” Current Opinion in that patients deal with it. Stress does cause a physiologic and disease activity during their first year of diagnosis. Pediatrics, v. 19 issue 5, 2007, p. 548-52. “if there is a way to know up front who is going to have response, but may cause one that actually increases this would help create a data entry system that could difficulties down the line, we could involve the appropriate 10 | research research | 11
    • Getting Cells to Tell are released, but these ions How do you get cells to tell have to return to their “stor- you what is happening? age facility” before the cell first, you have to make can contract again. When the them feel at home. cell isn’t functioning properly, it takes longer for the calcium When an organ is housed ions to return, slowing the inside the human body, it beating process, which is is exposed to blood, which represented by a flattened serves as the major source of out slope on the graph. energy. to extract cells from an organ outside of the body, When Cells Tell of you must supply an energy Heartbreaking News source. So the organ is “per- the ability to show exactly These graphs show the shortening and the relength- fused” by being placed in a what is going wrong within ening of a cardiac myocyte, a representation of its solution that is chemically a cell is proving to be an “heartbeat.” representative of blood. “We important part of disease try to trick them into think- diagnosis. “What we’ve ing they’re still in the body found is that the cells motion and performs mathematical and still healthy, but they’re actually in respond similarly to the whole organ conversions to represent the beat a dish in an incubator in artificial fluid,” and the whole organism,” said Dr. graphically, similar to the graph of a said Dr. Wold. this artificial fluid also Wold. once you get cells in the mood heart monitor. investigators can then contains an enzyme that breaks apart to communicate, they have plenty analyze the slopes on the graph to all of the scaffolding around the cells. to say about heart harming disease, determine whether or not the beating once the cells are exposed at their including type 2 diabetes. cell is functioning properly. rawest level, they are “suspended,” a As opposed to type 1 diabetes, in process that leaves them unattached if the graphical results reveal that the which a malfunctioning immune and floating in a special liquid bath. cell is not functioning properly, it is system doesn’t allow the pancreas to time to find out why. one way is by now the real, nitty gritty investigation produce insulin, the pancreas of a type looking at molecules involved in cell can begin. 2 diabetic creates plenty of insulin, but Listening to the Heart signaling. “cell signaling is the way the body stops reacting to it properly. “cardiac myocytes actually beat when a cell communicates within itself and this malfunction can lead to serious stimulated, just like the heart does. with other cells,” said Dr. Wold. one impacts on many systems of the body, that’s what makes up the of the cell signaling molecules of most including the heart. mechanics of the heart,” inSigHt fRoM tHe HeARt’S SMAlleSt MeSSengeRS said Dr. Wold. studying disease at the cellular level doesn’t “the main killer of ReveAlS eARlY WARningS of HeARt DiSeASe only help identify what doesn’t work for the diabetics is heart to get the cells to beat, disease. Most people more coaxing is required. heart, but also what does work, including W hen’s the last time you fist-sized organ is responsible for heart muscle, it has a story to tell. think that if diabetics talked to yourself? the truth one of the most vital life functions, that is, if you’re listening. “We use a device that therapeutic interventions like medication. take their medicine, stimulates the cell in is you’re doing it right now. pumping oxygen-rich blood through they’ll be fine, but that’s loren e. wold, phd, is listening. As the same way that the interest to Dr. Wold is the calcium ion blood vessels to reach the rest of the not the case,” said Dr. Wold. cells in the human body are living a principal investigator in the center nervous system would stimulate the because it regulates contraction and body. Although we are most used to heart to contract,” said Dr. Wold. While When type 2 diabetes is investigated at gossip mills. Sending and receiving for cardiovascular Medicine at the relaxation of the cell. listening to this big communicator this superfusion/stimulation chamber, the cellular level, the slope representing chemical messages along neural Research institute at nationwide with a stethoscope, research is which looks like a shallow, cylindrical Just like when the heart beats, there the relaxation phase of the heart beat pathways, firing synapses, exchang- children’s Hospital, Dr. Wold is showing that it’s worth getting dish with horizontal, metallic prongs are two phases involved when the cell is flattened out more than it would be ing gasses and elements, regulating studying heart function by taking a another perspective when it comes pointing inward, makes the cell beat, beats. the cell squeezes together in a healthy cell. this means that the temperature and cellular growth, big look at the smallest of parts. to studying heart disease. investigators view the cell through a during a contraction phase and then heart muscle is weakened for some your body is in constant conversation “in order to understand cardiology, you specialized microscope that captures returns to resting state (relaxation reason, which impacts the functioning with itself. Down at the cellular level lives the need to understand what is happening images of the beating in real time. A phase) before it can contract again. of the whole heart. cardiac myocyte, the heart’s smallest of all of the body’s conversationalists, at the cell level,” said Dr. Wold. program then analyzes the cell’s When the cell contracts, calcium ions messenger. Although it is simply a the heart is one of the biggest. this microscopic cell extracted from the 12 | research research | 13
    • Telling During Therapy Communicating with Human Cells “The only way we’re going to understand the whole heart Studying disease at the cellular level doesn’t only help iden- Most of Dr. Wold’s findings have come from investigating cells from animal and how it responds is to understand it at the cellular level.” tify what doesn’t work for models. As striking as the results may the heart, but also what does be, are they directly applicable to work, including therapeutic humans, specifically children? to help As one of the only places in the world so they can move to where they’re interventions like medication. understand just how translational the doing this, the learning curve is steep. needed and grow into heart cells. Right cellular findings are, Dr. Wold is “We’re just getting started on isolating now, this theory is just a theory, since it Many medications prescribed collaborating with alistair phillips, cells from these human samples. no has never been proven. to treat heart conditions, like one has published how to do this in Md, a cardiothoracic surgeon at those associated with type Dr. Wold would like to find a way nationwide children’s Hospital. pediatric samples, so we’re charting the 2 diabetes, inhibit the cell to isolate these progenitor cells to water and figuring out how to do it,” signaling process. by dissemi- “translational research needs to be a determine if they can indeed said Dr. Wold. isolating pediatric cells is nating the drug directly at the communication between scientists and transform into heart cells. After so unique because they are functionally cell level and monitoring the clinicians, in order to take findings from finding a way to isolate them, he different than adult cells; they respond effects, investigators can see the bedside to the bench top and vice plans to inject progenitor cells into to stress differently, so the isolation exactly how the cell reacts versa. Presently there is a lot of focus an animal model of hypoplastic left technique is much more sensitive. (and how the drug would on mouse models of a specific disease heart syndrome, a condition in which affect the entire heart). “We and equating what is happening in the the time is worth the effort, in Dr. the left ventricle is either very small need to understand the mouse to the human,” said Dr. Phillips. Phillips’ opinion. “We’re going to be or missing. He hopes that by mechanisms of heart cells in “if we can understand how individual able to take what we do in the clinical putting the cells in an environ- order to understand where cells of the heart work by examining realm and see what its benefit is on the ment where they are needed, they we can involve drug therapy human tissue, we can equate that to cellular level. With the ability to culture will grow to rebuild the damaged to adequately reverse this animal models of heart disease and individual cells, we’re going to be able heart. this research is of particular condition,” said Wold. clinical outcomes, with the result of to look into the microscope and say interest to Dr. Phillips since developing new strategies.” ‘this cell responds differently than this hypoplastic left heart syndrome the benefits of cellular cell because we did this procedure.’” is one if his clinical specialties. investigation don’t stop at to go beyond the animal model, drug investigation. other Dr. Phillips has received institutional this also has applications for the continued investigation into Loren Wold, PhD health treatment methods, Review board permission to extract tiny future design of clinical trials. “being progenitor cells could provide such as an increase in exercise pieces of heart tissue that are removed able to understand how the cell remarkable new insights into and improvement in diet, can normally and discarded during surgical responds at the cellular level overall heart functioning. “if we but according to Dr. Wold’s studies, a be viewed at the cellular level. correction of congenital defects. these and understanding the signaling can show how the heart regener- subject doesn’t have to be living with When Dr. Wold looked at the heart “explants” are then made available to mechanisms at each step along the ates, it has incredible implications diabetes for these heart conditions to cells of pre-diabetic rats once they were Dr. Wold to use for isolating individual way is the best way for drug develop- across the board,” said Dr. Phillips. be present. it can happen when lipid put on an exercise regime or fiber was human cells. With both specialists ment and testing,” said Dr. Wold. levels are heightened but glucose levels but before they look at the big added to their diet, all signs of heart working at nationwide children’s, the are normal (a condition known Sharing their “Stem Cell” Secrets picture, they have to continue to complications had disappeared. When handoff of the heart tissue typically clinically as pre-diabetes). “in some of the pediatric samples, look at the small one. the same diet and exercise routine takes about 10 minutes (as opposed we’ve found progenitor cells,” said Dr. these findings could have important was applied to cells in a diabetic state, to the time it takes to transport such a “the key is breaking down Wold. “Some people use the words implications for the pediatric a significant decrease in heart sample from one institution to another, cardiology to the functional unit, ‘stem cells,’ but we call them progeni- population. Although type 2 diabetes complications were shown. across town or even across country). which is the myocyte,” said Dr. tor cells because we’re not exactly sure is sometimes referred to as adult-onset Wold. “the only way we’re going Such investigation isn’t beneficial only Although such collaboration may what role they play,” said Dr. Wold. diabetes, it is no longer just an adult- to understand the whole heart and to diabetic-related heart diseases. the seem commonsensical, it is a rarity, hood disease. According to the centers As he explains it, these progenitor how it responds is to understand it same methods can be applied to look according to Dr. Wold. “We are one for Disease control, type 2 diabetes, cells are particularly common in at the cellular level.” at heart functioning, drug and treat- of the only pediatric institutes with this although still rare, is being diagnosed pediatric heart samples because ment performance in hypertension, kind of access. using human samples Further Reading: Wold, le., et al. “impaired more frequently in children and children’s hearts are still growing. no and heart conditions associated with and applying basic science concepts, SeRcA function contributes to cardiomyocyte adolescents, a striking phenomenon one knows exactly what they do, but dysfunction in insulin resistant rats.” Journal of Alistair Phillips, MD children who were born with fetal that’s translational research,” he said. Molecular and Cellular Cardiology, v. 39 issue 2, considering the prevalence of the theory is that they’re like the heart’s alcohol syndrome. 2005, p. 297-307. childhood obesity is on the rise. military, waiting for a sign of injury 14 | research research | 15
    • into the future | t H e look of ReSeARcH in 2012 While details are New Research Building Included in Campus Expansion Plans the Research institute at nationwide children’s Hospital continues to experience tremendous not finalized yet, growth and success. it is one of the fastest growing pediatric research centers in the united States in recent years, ranking in the top ten nationally in funding from the national institutes this graphic shows of Health. to accommodate the need for additional space, a third research building will be a glimpse of what added to the nationwide children’s campus. this vital space will enable nationwide children’s to continue recruitment of leading investigators and make possible scientific discoveries that is on the drawing may change the course of medicine and the lives of patients and families we serve. board for Nationwide the additional research building is part of nationwide children’s Hospital’s campus expansion plan. by 2012, the campus will have added more than 1 million square feet, including a new Children’s Hospital main hospital, making nationwide children’s Hospital one of the largest pediatric facilities in in 2012. the country. nonPRofit oRg. u.S. PoStAge pa I d coluMbuS, oH 700 children’s Drive PeRMit no. 777 columbus, ohio 43205-2696