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The Science and the Stories OF THE CHILDREN’S DISCOVERY INSTITUTE 2018 Report to Investors


The research funding you provide is an investment in people. It’s the critical support that talented physician-scientists need to continue to seek answers that will lead to better treatments for the array of diseases that threaten childhoods around the world.

Cover Photo: Ashanti, age 13, cystic fibrosis, double lung transplant in January

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A MESSAGE FROM

CDI Leadership

Thank you for believing in the brilliant minds of the Children’s Discovery Institute (CDI). Because of you, CDI researchers continue to leverage the discoveries made through the seed funding of their innovative ideas into larger research grants from such public funding sources as the National Institutes of Health. The research funding you provide is an investment in people. It’s the critical support that talented physician-scientists need to continue to seek answers that will lead to better treatments for the array of diseases that threaten childhoods around the world. Since the CDI’s inception in 2006, our researchers have made some profound discoveries. Standing shoulder to shoulder with them, you have enhanced their ability to harness the power of genomics in astonishing ways. Your support enables a better understanding of disease processes and the creation of personalized treatments for pediatric lung disease, pediatric leukemia and congenital musculoskeletal birth defects. Your investment has created pipelines for discovery of gene defects that negatively impact the development of the heart, lung, brain and immune systems. Because of you, our researchers have also been able to explore the dark corners of the gut microbiota, allowing for a better understanding of its role in health and disease. Each year, the CDI Scientific Advisory Board reviews dozens of research proposals. And though many are worthy of funding, only a precious few are selected. While not every study leads to a breakthrough, we risk missing out on discoveries that could propel us forward. That can mean some child somewhere in the world doesn’t receive a desperately needed treatment in time — because without research there is no progress. So, again, thank you for your critical support.

Gary A. Silverman, MD, PhD Executive Director Children’s Discovery Institute

Chairman, Department of Pediatrics The Harriet B. Spoehrer Professor of Pediatrics Washington University School of Medicine Pediatrician-in-Chief St. Louis Children’s Hospital

Mary C. Dinauer, MD, PhD Scientific Director Children’s Discovery Institute

Fred M. Saigh Distinguished Chair in Pediatric Research St. Louis Children’s Hospital

Joan Magruder (Ex Officio) President St. Louis Children’s Hospital

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FINANCIAL

Highlights $340 million

Center Award Totals

extramural grant funding obtained as a result of CDI awards

2006–2018

880

187 CDI Grants

Published Research Papers

6 Biology

& Physiology

awarded by department 2006–2018

Biology

2

3

Molecular Microbiology

1 Otolaryngology

5

8

Genetics

2

Center for Pediatric Pulmonary Disease

Congenital Heart Disease Center

Obstetrics & Gynecology

5

million

million

Mechanical, Aerospace & Structural Engineering

Neurosurgery

$18.6

5

million

Orthopedic Surgery

94

Pediatrics

Neurology

Science & Engineering

million

McDonnell Pediatric Cancer Center

$9.6

$11.1

1

7 Developmental 1 Computer

27

Grants

2 Chemistry

$13.8

CDI (all centers)

Medicine

1

$9.3

million

Biomedical Engineering

5 Cell Biology

$62.4 million

awarded since inception

as a result of CDI awards

By the Numbers total awarded to date

10 Pathology &

Immunology

2

Radiology

1

Center for Metabolism and Immunity

Radiation Oncology

1

Surgery– Pediatric


EXPANDING

Knowledge TO HELP KIDS REACH THEIR FULL POTENTIAL

“Right now, we can tell parents what to expect in terms of the surgical and medical treatments available for their newborn’s heart condition. Unfortunately, we can’t do the same for their long-term development. That uncertainty is what drives us to understand how and why brain development is different in these babies.” Cynthia Ortinau, MD, pediatrics

“Currently, no medical therapy for chronic pancreatitis (CP) exists, partly because it is so poorly understood. We seek to help clinicians understand the pathway between mutant digestive enzymes and a certain type of CP, then find drugs that can stop the disease before it takes hold. If successful, our findings will help greatly improve the quality of life for many children suffering the unbearable circumstances of CP.”

“If we find out what bacterial factors trigger immune protection, we might be able to develop a vaccine with that factor built into it. Our ultimate goal is to develop a whole new arsenal of different ways to inhibit the bacterium from causing infection before it gets started. Klebsiella (a dangerous and antibioticresistant bacteria) is not going to outsmart us for very much longer.” David Rosen, MD, PhD, pediatrics

Xunjun Xiao, PhD, pediatrics Stephen Pak, PhD, pediatrics

“What we know is that children who are reared in adverse settings, who experience deprivation, neglect, even abuse and trauma, experience physical and mental health problems at a disproportionate rate compared to their peers. But now, new data are emerging that suggest a link between adversity and changes in brain development. Our study will investigate the mechanistic pathways that lead to those changes.” Barbara Warner, MD, pediatrics Joan Luby, MD, psychiatry

“The only likely downside for re-purposing Glibenclamide (a diabetes drug) for Cantu syndrome (a rare congenital disorder) is its action on the pancreas to lower blood sugar levels. But a simple remedy should be to give glucose along with the medication. So it turns out that a spoonful of sugar may actually help the medicine go down, or at least work the way you want it to.” Colin Nichols, PhD, cell biology and physiology

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You Create the Stories of Healthier Futures

NEW LUNGS for

Ashanti

Imagine what it’s like for a teenager to consider a hospital her home away from home. That’s how Ashanti Dalton and her mom, Karen, feel about St. Louis Children’s Hospital. Ashanti has been a patient at St. Louis Children’s Hospital since she was an infant diagnosed with cystic fibrosis (CF), a chronic lung disease. Living with CF has led to her being in and out of the hospital through the years. She has battled multiple complications that led to a double lung transplant this past January.

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Over the years, Ashanti’s lungs had continued to worsen due to infection and inflammation, and Karen says they always knew a lung transplant would be in her future. “Children with cystic fibrosis have problems in other organ systems, but by far the greatest challenge is in the


NEW 2018 RESEARCH IN

Pulmonary Disease New funding from the CDI will pave the way for Jacco Boon, PhD, medicine, and Daisy Leung, PhD, pathology and immunology, to use advanced sequencing techniques to develop a muchlungs,” says Stuart Sweet, MD, PhD, medical director of the hospital’s pediatric lung transplant program. “If you look at the population of children who get lung transplants, anywhere from 40 to 60 percent of those patients have cystic fibrosis.” By Christmas of 2017, Ashanti was very sick and was placed on a waiting list for a new pair of lungs. Karen says, “I was so scared and nervous for Ashanti, but I had to stay positive for her. I’ll never forget the day we got the call. We were out shopping at T.J. Maxx and the phone rang. I put it on speaker and everyone around me heard the news and they were all congratulating Ashanti. It was just so nice.” On Jan. 6, 2018, Karen waited with family and friends during a very long surgery meant to give Ashanti a second chance at life, thanks to someone else’s kindness. Overall, her transplant was a success. However, complications unrelated to the new lungs caused her kidneys to fail and, thus, created the need for dialysis three days a week.

needed respiratory syncytial virus (RSV) vaccine. In a previous CDI-funded study, Dr. Leung played a key role in understanding how critical RSV proteins are structured. Could an inexpensive and readily available nutritional supplement, known as CoQ10, be the secret to preventing severe bacterial pneumonia in some children? CDI investigator Celeste Morley, MD, PhD, pediatrics, will seek to answer that question using a mouse model with a variant in a gene known to activate the enzymes the body needs to produce CoQ10, an antioxidant. With his funding, Timothy Wencewicz, PhD, chemistry, will take on mycobacteria and shortcircuit their ability to resist the antibiotics used to fight Mycobacterium tuberculosis (Mtb), which infects more than a million children annually. In children with cystic fibrosis, the inability to clear another type of mycobacteria from the lungs renders them unable to receive lung transplants. Dr. Wencewicz is taking an innovative approach to improve treatment results. Infectious disease specialist David Rosen,

Somehow, through it all, both Ashanti, now age 15, and her mom are grateful to the team of caregivers and the research that informs the prevention of chronic lung transplant failure. “I know everybody is going through a lot when they are at Children’s Hospital and it’s very hard. I feel for any parent going through what I’ve been through,” Karen says. “Some parents say, ‘Karen, I just can’t do it,’ and I say, ‘Yes, you can. It’s your child.’ I just keep thinking positive thoughts and keep a smile on my face.”

MD, PhD, pediatrics, received a CDI Faculty Scholar award to lead a study of Klebsiella pneumonia to uncover its vulnerabilities for vaccine development. Kel Vin Woo, MD, PhD, pediatrics, received a CDI postdoctoral fellowship to find ways to protect vulnerable premature infants from high blood pressure in the lungs, a condition known as pulmonary hypertension. He has identified promising targets that can prevent this disease in animal models, and he is further investigating the mechanism of this protective effect. 5


You Create the Stories of Healthier Futures

FIGHTING for

Colin’s Potential

Since 2014, when then 10-year-old Colin Schlereth was diagnosed with stage 4 medulloblastoma, the Schlereth family has been on a journey strewn with tears, fears, frustrations and triumphs. Medulloblastomas are fast-growing tumors that develop in a part of the brain that controls movement, balance and posture. Both the tumor and its treatment, which included proton beam radiation therapy and chemotherapy, sidelined Colin from hockey and hurt his school performance. “As a parent, it was devastating to see your son go from a healthy, active and thriving fourth-grader to one who was unable to write his name,” says Becky, Colin’s mother. According to CDI cancer researcher Josh Rubin, MD, PhD, pediatrics, cognitive deficits are the greatest obstacle to full functional recovery in the survivors of pediatric brain tumors. Now, CDI funding brings researchers in his lab together to answer an important question: can data, collected at the time of a child’s diagnosis, predict that child’s cognitive outcome? “Until we understand how tumors derail the structural and functional factors of brain development, it will be difficult for us to optimize cognitive recovery,” Dr. Rubin says. “Now, we don’t know how much influence genetics, environment and treatment have in determining outcomes.” 6


Working with the neuro-oncology team at St. Louis Children’s, Colin’s elementary and middle schools created altered educational plans for him. The goal ever since has been to help him keep pace without exhausting him. “Fortunately for us, both his schools have been amazing in providing us with resources for tutoring and in the level of support and caring they demonstrate,” says Becky. As Colin’s team of educators continue that support, Dr. Rubin and his colleagues have been collecting data generated by neuro-psychiatric testing, as well as functional and anatomical magnetic resonance imaging (MRI), of the brain tumor patients enrolled in their study. So far, they have exceeded the study’s initial enrollment goals. “We are hoping to gather enough data to apply for an NIH grant to really dig into this emerging issue,” Dr. Rubin says. “For now, we hope we can prove

“Until we understand how tumors derail the structural and functional factors of brain development, it will be difficult for us to optimize cognitive recovery.” Josh Rubin, MD, PhD

the feasibility of being able to do something with that data. Then, we hope to look for consistent patterns in the tumors of these patients. We also want to be able to identify the differences between brain tumor patients and a [healthy] control group. Eventually, we believe we will be able to give families an informed prediction on the cognitive outcome of various forms of treatment and adjust that child’s treatment accordingly. That would

be a truly transformative personalized medicine approach.” Meanwhile, Becky and her husband, Rick, will continue to do all they can to help Colin reach his full potential in school, on the ice and in life. “We are working very hard to get our Colin back,” says Becky. “We don’t need a rock star or a star athlete. We just want what he wants, and that’s to be in the game.”

NEW 2018 RESEARCH IN

Pediatric Cancer Cisplatin, a widely used and effective chemotherapy

Through advances in sequencing

drug, often causes hearing loss and nerve damage

technology, researchers are

in children who receive treatment. Mark Warchol,

discovering new gene variants

PhD, otolaryngology, and Lavinia Sheets, PhD,

in cancer cells all the time. The

otolaryngology, designed a study that addresses

ongoing challenge is that they

these issues. With their CDI funding, they hope

still don’t have a way to determine

to determine whether adjusting the treatment

their impact. Dustin Baldridge,

schedule based on a child’s biological rhythm, or

MD, PhD, pediatrics, Barak

Not pictured: Josh Rubin, MD, PhD

circadian clock, influences

Cohen, PhD, genetics, Josh Rubin, MD, PhD,

the vulnerability of sensory

pediatrics, Christina Gurnett, MD, PhD, neurology,

cells to the drug. They

Malachi Griffin, PhD, medicine, and Obi Griffin,

also will test to see if any

PhD, medicine, received CDI funding to perform

FDA-approved drugs and

the type of DNA scanning needed to make those

bioactive compounds could

determinations for two important cancer genes:

be used to prevent or reverse

TP53 and SMAD4. Their studies will be useful for

the nerve damage.

clinicians who treat cancer and promise to identify personalized therapies. 7


Investments in Discovery Create the Next Chapter of What Could Be

SAVING

Caroline

In one day, the Marnatti family’s world turned upside down. Their youngest daughter, Caroline, was admitted to the St. Louis Children’s Hospital pediatric intensive care unit (PICU) on Mother’s Day 2018. She was in toxic shock from an infection caused by Streptococcus, or “strep,” and it was impacting her heart, kidneys and lungs. “She very rapidly progressed from being critically ill to arriving at death’s door,” says critical care specialist Juliane Bubeck Wardenburg, MD, PhD, pediatrics. It quickly became clear that Caroline would need extracorporeal membrane oxygenation (ECMO), an advanced life support technique used for patients with life-threatening heart and/or lung problems.

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“Research has helped people like me, who are interested in infectious disease, understand the mechanisms of infection progression at a granular level,” Dr. Bubeck Wardenburg says. “We understand many details about how bacteria and toxins we fight work — we know that this is something that can be reversed, and that the body is capable of recovering from. In Caroline, we coupled this knowledge with


longstanding research and technical innovations that give us the ability to fully support heart and lung function by diverting a child’s circulation through a machine outside that child’s body — called ‘ECMO’ — which is really pretty amazing.” But, she adds, more still needs to be learned about how to avoid complications of using ECMO, like clotting or bleeding. Only through more research will clinicians be able to understand why some children put on ECMO do so much better than other children who need the support. In the case of children like Caroline, part of the answer to this question may lie in understanding more about infection and the immune system. “Today,” says Dr. Bubeck Wardenburg, “when I talk to parents about putting their child on ECMO, if they ask about likelihood of survival, I tell them that they may have a 50 to 70 percent chance of leaving the hospital. But the truth is that some may have more than a 90 percent chance of survival while others may have a very low chance. Right now, I can’t say with any certainty what the actual outcome will be based on the child’s individual response to disease. Caroline’s case affords us the opportunity to harness molecular, cellular and technological medicine and apply it to a single child. It is research that will deepen our ability to understand disease and best apply interventions to improve outcomes.” Fortunately, Caroline was able to go off ECMO and to pull through her illness. She now is in outpatient rehabilitation through St. Louis Children’s Hospital, and also receives unique care in the Neurocritical Care Follow-up Program, the first of its kind in the nation to provide a seamless continuum of clinical care for PICU patients and their families. The program, which just received philanthropic support to expand its clinicians’ ability to follow child development and perform outcomes

research, has a primary goal of ensuring that families leave the hospital able to resume their lives to the fullest. “I came back to St. Louis Children’s Hospital and joined the Washington University School of Medicine faculty because this place has an almost magical feel for a physician-scientist,”

says Dr. Bubeck Wardenburg. “There is so much investment here in understanding disease and enabling those of us who think about molecular mechanisms of disease and how they inform the clinical arena. If I were an investor, I would be confident that the integration between clinicians and researchers is profoundly different here.”

NEW 2018 RESEARCH IN

Metabolic & Immune Disease Ana Maria Arbelaez, MD, pediatrics, and Christopher Smyser, MD, neurology, seek to understand the neurodevelopmental consequences of malnutrition in children. The researchers and their collaborators will use their funding to expand a previous CDI-funded pilot study in Cali, Colombia. Harshad Ingle, PhD, medicine, received a postdoctoral fellowship to study how malnutrition affects the microbial makeup of a child’s gut and leads to severe virus-induced diarrhea. With their CDI funding, Xunjun Xiao, PhD, MS, pediatrics and Stephen Pak, PhD, pediatrics, will study how inherited mutations in a pancreatic digestive enzyme cause a cellular response that leads to chronic pancreatitis. Greater understanding of this disease, which can result in diabetes, chronic pain and the inability to digest food, could lead to effective therapies, which currently are lacking.

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Investments in Discovery Create the Next Chapter of What Could Be

Personalized MedicineA NEW,

EXPANDED VISION FOR THE CDI The battle between health and disease has been fiercely waged throughout St. Louis Children’s Hospital and in the research labs at Washington University School of Medicine since their inception. But now, a bold and brilliant team of physicians and research scientists are wielding new, more precise weaponry. Personalized or precision medicine, defined as the use of genomics to identify, prescribe and treat disease, is becoming a reality for every childhood malady. And the CDI is at the forefront of discovering new precision therapies designed for individual patients. In the first decade of this partnership between two powerful institutions to transform child health care, the CDI has focused its resources on four main centers of research: • Center for Pediatric Pulmonary Disease • Congenital Heart Disease Center • Center for Metabolism and Immunity • McDonnell Pediatric Cancer Center

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Through this vision, the CDI could help ensure that children reach their full potential.

Powered by the support of forward-thinking philanthropists, the mission of the CDI could expand to include the following: 1. Leverage the Washington University School of Medicine’s personalized medicine resources to establish complementary and overlapping pediatric scientific centers that use genomics and multi- or interdisciplinary approaches to attacking pediatric disorders.

NEW 2018 RESEARCH IN

Metabolic & Immune Disease

2. Integrate aspects of the research program with patients by coupling each center to multiple clinical programs at the hospital and/or regional/national patient networks.

Leveraging her

3. Broaden the overall scope of the pediatric research programs supported to encompass all childhood diseases.

molecular mechanisms

understanding of the of immunodeficiency,

4. Use center directorships to recruit and retain the best and brightest minds in pediatric research and clinical care.

Megan Cooper, MD,

5. Integrate centers into training pipelines that foster and support the development and recruitment of emerging pediatric research talent.

use advanced genome

6. Broaden the spectrum of philanthropic interest and support. 7. Integrate every child’s genomic profile, with ageand disease-related changes to their microbiome and metabolome, into their lifelong medical record. 8. Enhance technology development and transfer. Through this vision, the CDI could help ensure that children reach their full potential. It could address health disparities between our communities. It could give hope to families looking for a diagnosis of their child’s rare disease or structural birth defect.

PhD, pediatrics, will sequencing to uncover personalized precision therapies based on the specific mutations causing a child’s immune disorder. Does adversity become “biologically embedded” in a child, leading to disparities in health outcomes? A new study by Barbara Warner, MD, pediatrics, and Joan Luby, MD, psychiatry, will investigate the degree to which psychosocial stress, such as poverty, in the prenatal period or early infancy alters the microbial makeup of the baby’s gut and, in turn, his or her immune system health and inflammatory response.

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CURRENT

Research Grants Congenital Heart Disease Center

McDonnell Pediatric Cancer Center

Meghan Chlebowski, MD, pediatrics Technology-based Educational Modules for Patient and Family Education

Dustin Baldridge, MD, PhD, pediatrics Barak Cohen, PhD, genetics Joshua B. Rubin, MD, PhD, pediatrics Christina Gurnett, MD, PhD, neurology Malachi Griffith, PhD, medicine Obi L. Griffith, PhD, medicine High-throughput, Large-scale Functional Genomics of Genetic Variation in Pediatric Cancer

Joel Garbow, PhD, radiology Effect of Elastin Insufficiency on Brain Development and Cognition Kory Lavine, MD, PhD, medicine Christopher Sturgeon, PhD, medicine Pluripotent Stem Cell-derived Macrophages as a Therapeutic for Pediatric Dilated Cardiomyopathy Cynthia Ortinau, MD, pediatrics Underlying Mechanisms of Impaired Brain Development in Congenital Heart Disease Jennifer Silva, MD, pediatrics Jonathan Silva, PhD, biomedical engineering Improving Outcomes in the Pediatric Cardiac Catheterization Lab Using Augmented Reality Kel Vin Woo, MD, PhD, pediatrics Protective Role of Endothelial Fibroblast Growth Factor Signaling in Group 3 Pulmonary Hypertension

Hong Chen, PhD, biomedical engineering Yongjian Liu, PhD, radiology Image-guided Drug Delivery for Improved Treatment of Diffuse Intrinsic Pontine Glioma John F. DiPersio, MD, PhD, medicine Matthew Cooper, PhD, medicine Clinical Development of CRISPR/Cas9 Gene-edited CAR-T for the Treatment of T Cell Malignancies Todd Fehniger, MD, PhD, medicine Memory-like Natural Killer Cell Immunotherapy for Pediatric and Young Adult Leukemia Patients Karen Gauvain, MD, pediatrics Gavin Dunn, MD, PhD, neurosurgery A Pilot Study of a Personalized Vaccine Approach in Patients with Recurrent Pediatric Brain Tumors Karen Gauvain, MD, pediatrics David Limbrick, MD, PhD, neurosurgery MRI-guided Laser Heat Ablation to Induce Blood Brain Barrier Breakdown in Pediatric Brain Tumors Jeffrey Magee, MD, PhD, pediatrics Developmental Changes in Stem Cell Self-renewal Mechanisms and Their Role in Leukemogenesis Rob D. Mitra, PhD, genetics Sex-specific Super Enhancer Activity in Glioblastoma

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Center for Metabolism and Immunity Ana Maria Arbelaez, MD, pediatrics Christopher Smyser, MD, neurology Effects of Childhood Malnutrition on Brain Development Regina Clemens, MD, PhD, pediatrics The Molecular Regulation of Neutrophil Calcium Signaling in Acute Lung Injury Megan Cooper, MD, PhD, pediatrics Investigation of Mechanisms of Pediatric Immune Dysregulation Brian DeBosch, MD, PhD, pediatrics Role of Enterocyte GLUT9 in Intestinal Urate Handling and Energy Homeostasis McDonnell Pediatric Cancer Center (cont.) Joshua Rubin, MD, PhD, pediatrics Albert Kim, MD, PhD, neurosurgery Kristen Kroll, PhD, developmental biology Hiroko Yano, PhD, neurosurgery Targeting the Abnormal Chromatin State of Pediatric Brain Tumors Joshua Rubin, MD, PhD, pediatrics Bradley Schlaggar, MD, PhD, neurology Survivors of Pediatric Brain Tumors: Biomarkers of Cognitive Dysfunction Shalini Shenoy, MD, pediatrics A Phase I Trial of Familial Haploidentical Nonmyeloablative Bone Marrow Transplantation in Children Mark Warchol, PhD, otolaryngology Lavinia Sheets, PhD, otolaryngology Prevention of Sensory Pathology Following Cisplatin Chemotherapy

Brian DeBosch, MD, PhD, pediatrics Paul Hruz, MD, PhD, pediatrics Prevention and Treatment of Hepatic Steatosis Through Selective Targeting of GLUT8 Misty Good, MD, pediatrics Modulating the Intestinal Immune Response in the Pathogenesis of Necrotizing Enterocolitis Harshad Ingle, PhD, medicine Effects of Malnutrition on Innate Immune Regulation of Norovirus Clifford Luke, PhD, pediatrics Stephen Pak, PhD, pediatrics High Content Drug Screens for the Prevention of Necrotizing Enterocolitis Jonathan Miner, MD, PhD, medicine Robyn Klein, MD, PhD, medicine Neurodevelopmental Implications of Congenital Zika Virus Infection

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Center for Metabolism and Immunity (cont.) David Rosen, MD, PhD, pediatrics Klebsiella Pneumoniae Virulence Factor Regulation and Host Immune Response in the Lung David Rudnick, MD, PhD, pediatrics Stephen Pak, PhD, pediatrics Discovering Novel Therapeutic Interventions for Alpha-1-antitrypsin Deficiency Liver Disease Brigida Rusconi, PhD, pediatrics Metabolomic and Experimental Investigation of Host Lipids in Necrotizing Enterocolitis Onset Kristen Seiler, MD, surgery Development of Patient-derived Small Intestine “Organ-on-Chip� Microfluidic Devices Indi Trehan, MD, MPH, pediatrics Innovative Interventions for Improving Childhood Growth and Environmental Enteropathy Indi Trehan, MD, MPH, pediatrics Mark Manary, MD, pediatrics Optimizing Therapeutic Foods for Neurocognitive Development in Malnourished Children Barbara Warner, MD, pediatrics Impact of Childhood Intestinal Microbial Maturity on Nutritional Status and Immunity Barbara Warner, MD, pediatrics Joan Luby, MD, psychiatry The Gut Microbial Contribution to Systemic Inflammation and Moderating Role of Psychosocial Stress Timothy Wencewicz, PhD, chemistry Blocking Nitrogen Metabolism in TB Xunjun Xiao, PhD, pediatrics Stephen Pak, PhD, pediatrics Development of Novel Therapies for Chronic Pancreatitis by Targeting Misfolded Digestive Enzymes

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Center for Pediatric Pulmonary Disease Leonard Bacharier, MD, pediatrics Avraham Beigelman, MD, pediatrics Upper Respiratory Tract and Fecal Microbiomes and Recurrent Wheezing Following RSV Bronchiolitis Joshua Blatter, MD, MPH, pediatrics David Wang, PhD, molecular microbiology Identifying Biomarkers in Pediatric Lung Transplantation Using the Complete Microbiome Jacco Boon, PhD, medicine Daisy Leung, PhD, pathology and immunology Live-attenuated RSV Vaccines: An RNA-based Approach to Attenuate Virus Replication


Center for Pediatric Pulmonary Disease (cont.) Regina Clemens, MD, PhD, pediatrics The Molecular Regulation of Neutrophil Calcium Signaling in Acute Lung Injury Jeffrey Haspel, MD, PhD, medicine Impact of the Circadian Clock and Age on Antiviral Responses that Contribute to Asthma Celeste Morley, MD, PhD, pediatrics Evaluating a Genetic Variant in COQ6 Predisposing to Severe Childhood Pneumonia Jessica Pittman, MD, MPH, pediatrics Dmitriy Yablonskiy, PhD, radiology Determinants of Change in Lung Function During Pulmonary Exacerbation and Recovery in Cystic Fibrosis David Rosen, MD, PhD, pediatrics Klebsiella Pneumoniae Virulence Factor Regulation and Host Immune Response in the Lung

All Center Grants F. Sessions Cole, MD, pediatrics David Spencer, MD, PhD, medicine Karyn Meltz Steinberg, PhD, pediatrics Comprehensive Genome Analysis for Discovery of Missing Heritability in Infants with Birth Defects Todd Druley, MD, PhD, pediatrics Rob Mitra, PhD, genetics Accelerating Novel Genetic Discoveries by CDI Investigators via Next-generation DNA Sequencing Phyllis Hanson, MD, PhD, cell biology and physiology Paul Taghert, PhD, neuroscience Washington University Center for Cellular Imaging Collaboration with the Children’s Discovery Institute Ericka Hayes, MD, pediatrics Summer Pediatric Research in Global Health Translation (SPRIGHT)

Timothy Wencewicz, PhD, chemistry Blocking Nitrogen Metabolism in TB

Kathryn Miller, PhD, biology Support for Undergraduate Research in Children’s Health and Disease

Kel Vin Woo, MD, PhD, pediatrics Protective Role of Endothelial Fibroblast Growth Factor Signaling in Group 3 Pulmonary Hypertension

Lilianna Solnica-Krezel, PhD, developmental biology Zebrafish Models for Pediatric Research – Zebrafish Research Cooperative Philip Spinella, MD, pediatrics Implementation of Science Principles to Develop Blood Management Guidelines for Critically Ill Children

“There is so much investment here in understanding disease and enabling those of us who think about molecular mechanisms of disease and how they inform the clinical arena. If I were an investor, I would feel confident that the integration between clinicians and researchers is profoundly different here.” Juliane Bubeck Wardenburg, MD, PhD

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CHILDREN’S DISCOVERY INSTITUTE

Leadership

CDI Scientific Advisory Board Aaron DiAntonio, MD, PhD, is the Alan A. and Edith L. Wolff Professor of Developmental Biology at Washington University School of Medicine. He is also a past chair of the NIH Synapses, Cytoskeleton and Trafficking study section. Michael J. Bamshad, MD, is the Allan and Phyllis Treuer Endowed Chair in Genetics and Development at Seattle Children’s Hospital and professor of pediatrics and genome sciences at the University of Washington School of Medicine. Mario Castro, MD, MPH, is the Alan A. and Edith L. Wolff Professor of Pulmonary and Critical Care Medicine at Washington University School of Medicine and a noted authority on asthma and other respiratory diseases. Susan K. Dutcher, PhD, is a professor of genetics and of cell biology and physiology, and the interim director of the McDonnell Genome Institute at Washington University School of Medicine. Dr. Dutcher is interested in the basic biology of cilia. Cilia are required for many developmental processes, including left-right asymmetry, heart development, maintenance of the renal epithelium, respiratory function, electrolyte balance in the cerebrospinal fluid and fertility. Jay Kolls, MD, is a professor of medicine and pediatrics, director of the Center for Translational Research in Infection and Inflammation and the John W. Deming Endowed Chair in Internal Medicine at the Tulane University School of Medicine.

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Jeanne Nerbonne, PhD, is the Alumni Endowed Professor of Molecular Biology and Pharmacology in the departments of Developmental Biology and Medicine, the Co-Director of the Center for the Investigation of Membrane Excitability Diseases, and the Director for the Center for Cardiovascular Research at Washington University School of Medicine.

CDI BOARD MEMBER RECEIVES British

Royal Society’s Highest Honor Jeffrey I. Gordon, MD, pathology and immunology, a member of the CDI Board of Managers, recently received the 2018 Copley Medal from the Royal Society in Britain. He is being honored for his studies of human gut microbial communities, which have led to a fundamental shift in the way scientists understand the relationship between microbes, health and disease. His discoveries have shed new light on, among other things, the origins of two pressing global health problems: obesity and childhood malnutrition. Dr. Gordon is in good company. The Copley Medal, the most prestigious scientific award in the United Kingdom, is given annually for outstanding achievements in research in any branch of science. Past recipients include Benjamin Franklin, Charles Darwin, Louis Pasteur, Albert Einstein and Stephen Hawking.


Board of Managers Andrew E. Newman, Chair Chairman Hackett Security, Inc.

Richard J. Mahoney Retired Chairman and Chief Executive Officer Monsanto Company

Dale L. Cammon Chairman and Co-Chief Executive Director Bryant Group, Inc.

Distinguished Executive in Residence Weidenbaum Center on the Economy, Government and Public Policy Washington University in St. Louis

Daniel Getman, PhD Retired President Kansas City Area Life Sciences Institute

Richard H. McClure Former President UniGroup, Inc.

Former Vice President Pfizer R&D Director St. Louis Laboratories

James S. McDonnell III Retired Corporate Vice President McDonnell Douglas Corporation

Jeffrey I. Gordon, MD Dr. Robert J. Glaser Distinguished University Professor

Jeffrey Milbrandt, MD, PhD The James S. McDonnell Professor of Genetics Washington University School of Medicine

Director The Edison Family Center for Genome Sciences and Systems Biology Washington University School of Medicine

John O’Connell Vice Chairman Bodley Group

Keith S. Harbison Managing Partner Alitus Partners, LLC

David H. Perlmutter, MD (Ex Officio) George and Carol Bauer Dean, School of Medicine

Jennifer K. Lodge, PhD Professor Molecular Microbiology

Executive Vice Chancellor for Medical Affairs Washington University School of Medicine

Associate Dean for Research Washington University School of Medicine Vice Chancellor for Research Washington University Joan Magruder (Ex Officio) President St. Louis Children’s Hospital

Spencer T. and Ann W. Olin Distinguished Professor

Gary A. Silverman, MD, PhD Executive Director Children’s Discovery Institute Chairman Department of Pediatrics The Harriet B. Spoehrer Professor of Pediatrics Washington University School of Medicine Pediatrician-in-Chief St. Louis Children’s Hospital Raymond R. Van de Riet, Jr. President Aero Charter, Inc. Kelvin R. Westbrook President and Chief Executive Officer KRW Advisors, LLC


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St. Louis Children’s Hospital Foundation 1001 Highlands Plaza, Suite 160 St. Louis, MO 63110 888.559.9699 or 314.286.0988 childrensdiscovery.org

The Children’s Discovery Institute is a multidisciplinary, innovation-based research partnership between St. Louis Children’s Hospital and Washington University School of Medicine. Launched in 2006, the Institute is focused on accelerating discoveries in pediatric research to ultimately find cures for the most devastating childhood diseases and disorders. Thank you for the support that makes you a Guardian of Childhood. Learn more at childrensdiscovery.org.

Children's Discovery Institute: 2018 Report to Investors  
Children's Discovery Institute: 2018 Report to Investors