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Bright minds. Bright future. 2014 Report to Investors

A Message from the Institute Leadership

Bright minds. Bright future. We hope you enjoy reading the 2014 Children’s Discovery Institute (CDI) Investor Report. Its oversized design mirrors the big impact our researchers have made in 2014. It is bright and bold to reflect the optimism of our investigators, displayed every day through their willingness to seek new pathways to treatments and cures for childhood disease. We launched the CDI with some important objectives in mind, most notably, attracting and retaining the best and brightest young scientific talent in the country (and world) to advance research in childhood disease. This year’s four featured investigators exemplify the inspiring inquisitiveness of these talented researchers. As you read about the questions they are asking and gains they have made in understanding leukemia, lung infections, congenital heart disease and scoliosis, we think you’ll be inspired by their tenaciousness and passion. And, once you learn about the journeys of the patients

we’ve featured, you will understand their dedication. Every child treated at St. Louis Children’s Hospital inspires our clinicians and researchers to collaborate, to ask why, to inquire what can we do better and how can we make a difference. Included in this year’s report are summaries of the insights CDI investigators have contributed to the pediatric landscape in 2014. They represent brilliant research ideas and efforts from multiple academic departments across Washington University. Like pebbles dropped into a lake, each has a ripple effect of monumental reach. Each discovery made will have an immeasurable impact on the lives of children, now and in the future. When St. Louis Children’s Hospital and Washington University School of Medicine embarked on the journey of the CDI eight years ago, we had high hopes that we could reshape pediatric medicine. And we still do. How can we not when we have the brightest minds working together to ensure that every child has a bright future?

Mary C. Dinauer, MD, PhD

Alan L. Schwartz, PhD, MD

Lee F. Fetter

Scientific Director Children’s Discovery Institute

Executive Director Children’s Discovery Institute

President St. Louis Children’s Hospital Foundation

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

The Harriet B. Spoehrer Professor of Pediatrics


Pediatrician-in-Chief St. Louis Children’s Hospital

Inspiring Investors for 8 Years

“ The Children’s Discovery Institute is doing breakthrough research now. Where better to start than with kids? They are our future.” JoAnn and Don Shaw

“ The Children’s Discovery Institute is a good bang for your buck. We’ve seen some results already, and since we’re dealing with kids, they have a long life ahead of them, so the payback is long-term.”

“With NIH funding going down, some of the riskiest, most highly impactful research just doesn’t get done because they’re only looking for the safe bet, the single or the double. I think it would be great to just go for the home run.”

Chuck and Jan Mueller

Jim Johnson

“ What’s fascinating is that the research being done through the Children’s Discovery Institute is relevant to the world. If just one of these diseases is cured, it’s cured for the world, not just for St. Louis or the United States.” Michelle Trulaske 1

Congenital Heart Disease Center

Probing a remaining mystery of congenital heart disease bright mind

Jennifer Duncan, MD As a pediatric intensive care doctor, Dr. Jennifer Duncan takes care of some of St. Louis Children’s Hospital’s sickest children. She meets families at the most dire times of their lives and supports them on their journey. She admits that it might get a little overwhelming if she didn’t have another professional outlet. But as one of the CDI’s first faculty scholars, Dr. Duncan is able to step away from the bedside and into the laboratory where she can look at the problems she confronts clinically under an entirely different light. “Deciding to do a critical care fellowship gave me the opportunity to return to the lab. That’s when I realized I wanted to build a career that combined clinical work and research. When I joined the faculty here I found a great mentor and knew that I’d made the right decision to take my career in this direction.” In her lab, Dr. Duncan looks to explain why some children with congenital heart disease do much better after surgery than others with seemingly the same problem. “Not being able to predict how a child responds to treatment got me thinking about whether the health of the mother makes a difference, and if so, would it help to intervene earlier.” What doctors do know is that children with congenital heart disease are more likely to have mothers with obesity issues or diabetes. But what is the connection? Dr. Duncan believes it has something to do with the metabolic programming that occurs during the time that the fetal heart is developing. “So the more we can understand about how mom’s nutritional status affects the baby’s metabolism, the better we’ll be able to develop new strategies to keep congenital heart defects from developing or improve outcomes for patients who require surgery.” Jennifer Duncan, MD, pediatrics, meets families at the most dire times of their lives and supports them on their journey.


Congenital heart defects affect nearly 40,000 infants born in the United States each year.

“There may be dark times, there may be challenges in life, but then the hope comes in at a certain point in the song where you can see light and you can see

In the United States, hospital costs for people with a heart defect were about $1.4 billion in one year.

tomorrow and you can see all the potential life has.” The cause of most congenital heart defects remains unknown.

Erin Bode, singer/songwriter

bright future

Katelyn, age 12 It has been a bumpy road for Katelyn and her family since her first open-heart surgery at 4 months old. Katelyn was born with a heart defect called complete AV canal. Instead of four separate chambers, she had a hole in her heart where all the blood — oxygenated and non-oxygenated —  ran together. To date, she has had seven surgeries and may need more as she ages. Until then, she is healthy and happy enjoying the life of a typical pre-teen. But not every little girl can say they’ve had a song recorded just for her. With great honesty and candor, Katelyn shared the details of her personal journey with St. Louis singer and songwriter, Erin Bode. Erin poured all those emotions into the song “The Space Between.” In addition to the sentiments behind the lyrics, Erin borrowed one more thing from Katelyn. With the help of Dr. George Van Hare, Louis Larrick Ward Professor of Pediatrics and co-director of the St. Louis Children’s and Washington University Heart Center, Erin was able to use a recording of Katelyn’s heartbeat as the rhythm track for the song. “We wanted to make sure that we took people on a journey and allowed them to feel some of the challenges that one goes through when they are dealing with an illness,” explains Bode. Music is just the latest tool Katelyn has used to share her story and provide hope to others. She raised money for heart disease research by jumping rope; she personally delivered valentines to young heart patients; and she donated her own gift cards to families in the Maxine Clark and Bob Fox Cardiac Intensive Care Unit. “She wanted the moms and dads of those babies to know there is hope,” says Katelyn’s mom, Karin. “It is challenging, and every day here may be hard, but she just wanted them to see that there is life after this.” Katelyn, left, inspired Erin Bode to write a song. To hear it, visit stlouischildrens.org and search for “The Space Between.”


McDonnell Pediatric Cancer Center

Finding better, safer treatments for childhood leukemia bright mind

Grant Challen, PhD An Australian-born scientist, Dr. Grant Challen came to the United States in 2006 to pursue a post-doctoral research fellowship at Baylor College of Medicine. Next, he made his way to Washington University School of Medicine because he wanted to make an impact on childhood diseases with poor prognoses, and thought this was the place to pursue that vision. Acute lymphoblastic leukemia (ALL) became an obvious choice. Although much progress has been made in its treatment, some subgroups of this disease, such as T-cell ALL, remain difficult to treat without toxicity. And even then the outcomes are spotty. When, a couple of years into his work, Dr. Challen watched a young family he’d met experience the perilous journey of pediatric ALL treatment only to have their 3-year-old succumb to the disease after a relapse, he was reassured he’d picked the right fight. “I saw the full gamut of their emotions as they went through the experience —  from the original diagnosis to the recovery and relapse. The level of stress this kind of disease creates in a family made a personal impression on me. I have young children of my own, but can only imagine the devastation.” People with T-cell ALL have cancerous, immature white blood cells in their blood. Their overwhelming presence inhibits the production of infectionfighting white blood cells and oxygen-carrying red blood cells. Dr. Challen’s CDI-funded project looks at mutated enzymes known to create this disease. “We think it’s an important area to study,” he says. “If we can identify new ways to treat patients with these particular mutations and better tailor the chemotherapy we currently prescribe, the long-term quality of life for these children will improve.”

Grant Challen, PhD, medicine (right) uses his CDI grant to fight for the same kids Alok Kothari, MD, pediatrics, treats as a pediatric hematology/ oncology clinical fellow.


Today, in the CDI’s McDonnell Pediatric Cancer Center, three research studies are focused on different forms of childhood leukemia.

Pedal the CauseTM raises millions for the pediatric and adult cancer research conducted at St. Louis Children’s Hospital and Siteman Cancer Center.

Each year, there are about 2,900 new cases of children and adolescents diagnosed with ALL in the United States alone.

bright future

D.J., age 6 It’s always devastating to hear the words “your child has leukemia.” But, when you’re a very young mother, it can be particularly crushing. Shakila, age 19, was heading home from St. Louis Children’s Hospital, where she and her boyfriend, Darnell, had taken their 3-year-old, D.J., for blood work. Days earlier, she noticed a knot on his leg, which was tender to the touch. Shakila and D.J. spent the next three months at St. Louis Children’s Hospital battling through an intense round of chemotherapy. Shakila had to quit her job to give her son the attention he needed. Darnell worked extra shifts to ensure they could stay in the apartment they’d rented. Life after discharge changed, too. “Everything was so different. His immune system was suppressed, so we couldn’t go outside. And he couldn’t go to preschool or anything, so I made sure he learned his letters and could write his name.” Fortunately, D.J. sailed through his cancer treatment relatively unscathed. He rang the bell, a ritual all St. Louis Children’s Hospital patients who finish their chemotherapy enjoy, on July 29, 2014 and started school this fall. Meanwhile, Shakila, a former high school basketball star, let the experience of seeing her child through cancer treatment shape her current career path to become a nurse anesthetist. D.J.’s bravery and the grace and strength his young mother displayed during his cancer treatment got the attention of someone who is no stranger to conquering seemingly insurmountable challenges. Teri Griege didn’t just complete the 2011 Ironman World Champion triathlon in Kona, Hawaii, she did so while undergoing treatment for stage-4 colon cancer. Since that momentous event, Teri has continued her fight against cancer and has inspired more than 100 athletes to join her Powered by Hope team for the annual Pedal the Cause™ ride in St. Louis. Free from leukemia, D.J. was ready to start school this fall and inspired Teri Griege’s Pedal the Cause™ team to go the extra mile for cancer research.

This year, the Powered by Hope team rode in honor of D.J. “He is a very special little boy, and you can’t help but be inspired by Shakila.” Teri says, “I’m delighted to ride in their honor.”


The Center for Musculoskeletal and Metabolic Disease

Discovering the genetics behind scoliosis bright mind

Christina Gurnett, MD, PhD Not everyone can say that conversations around the family dinner table inspire scientific research projects that lead to promising discoveries. But, when those dinners involve a pediatric neurologist trained in genetics research and a pediatric orthopaedic surgeon, it’s bound to happen. In fact, that’s where Dr. Christina Gurnett’s CDI-funded research of scoliosis got its start. “One of the reasons my husband (Matthew Dobbs, MD) became a pediatric orthopaedic surgeon was because his sister developed scoliosis as a teenager. She can tell stories about being told by her doctor that she had to wear a brace under her clothes and that it may not even help, in which case she would have to undergo corrective surgery. Not much has changed all these years later, which got us thinking that there must be a way to expand upon those treatment options.” Now, 1,000 banked patient samples and thousands of curve-spined zebrafish later, Dr. Gurnett is beginning to amass the evidence needed to create those innovations. Her research, launched with a CDI grant in 2007, has identified genetic risk factors that predispose children to develop S-shaped scoliosis curves dramatic enough to require surgery. The findings, which appeared in Human Molecular Genetics this fall, indicate that drugs currently in clinical trials for a related disorder may eventually be used to prevent scoliosis in some children who carry mutations to fibrillin-1 and fibrillin-2 genes. Fibrillin-1 is an important protein that connects cells and tissues together throughout the body. “Other genes are involved in scoliosis, as well, but this is a good start,” Dr. Gurnett says. These encouraging findings lead Dr. Gurnett to believe that there will come a day when a child’s pediatrician can detect the gene mutation and therapeutically intervene before scoliosis ever has a chance to develop, sparing the child from bracing and, in some cases, surgery. They also offer Dr. Gurnett something she can point to when her children complain about boring science conversations. They really do make a difference.


Christina Gurnett, MD, PhD, neurology, seeks new treatments for scoliosis.

More than 80% of people who develop scoliosis over the age of 10 are girls.

The simple act of trying to hem a dress clued Lydia’s parents into the possibility of her developing scoliosis.

Scoliosis can cause shortness of breath and chest pain due to the condition’s interference with the function of the lungs and heart. Braces, which must be worn 24 hours a day in severe cases of scoliosis, don’t correct the spinal curve, just keep it from getting worse.

bright future

Lydia, age 14 Just one more cartwheel. That’s what Lydia wishes she had done before her spinal surgery to correct severe scoliosis last spring. Despite having worn a cumbersome brace for four long years, Lydia required a more invasive procedure involving steeling her spine with three titanium rods and 22 screws. The surgery has temporarily sidelined this high school freshman from basketball, volleyball and soccer this year and has put a complete kibosh on cartwheels. The silver lining is that she has more time to pursue her other passions: theater, music and writing. Scoliosis is more common in girls than boys. In fact, Lydia and her older sister Miranda were diagnosed around the same time. Miranda was 14. Lydia was 10. At first, they supported each other through the 20-hour-a-day bracing. But, perhaps because of its early onset, Lydia’s spine didn’t respond to the bracing as well as Miranda’s did, so she had to endure it long after Miranda was able to leave it behind. “That’s when it got really hard,” Lydia says. “It just became more and more difficult to fit it into my life. It was hot, and I had to wear a t-shirt with it. It limited the kind of clothes I could wear. And I love clothes and shopping.” But the worst part, she says, was the questions about bracing. “Having to explain it over and over got pretty annoying,” she says. Couple her brace fatigue with a noticeable increase in back pain due to a growth spurt, and Lydia and her parents, Bob and Lucinda, knew it was time for more intervention. Recovering nicely from her April 2014 procedure, Lydia says she looks forward to trying out for her school’s athletic teams next fall.

Lydia stands taller, straighter and ready for anything life brings.

“I can see the light at the end of the tunnel, and that’s a very good thing,” Lydia says.


Center for Pediatric Pulmonary Diseases

Lung disease meets its match bright mind

Christina Stallings, PhD Dr. Christina Stallings joined the Washington University School of Medicine faculty after a fellowship at Sloan-Kettering Institute in New York. Her intention in coming here was to study how tuberculosis develops. The antibiotic-tolerant airborne bug, which kills more than one million people a year, is a prominent worldwide public health problem. But, when Dr. Stallings arrived at what she calls a mecca for the study of microbial pathogenesis, another pathogen entered her crosshairs. All the pediatric infectious disease clinicians she spoke to cited Mycobacterium abscessus (Mabs) as the mycobacterial infection that most keeps them up at night. When the almost-impossible-to-treat infection opportunistically attacks children with cystic fibrosis, it doesn’t let go, overwhelming their vulnerable immune systems and knocking them off the list for lung transplant. “It definitely tugs at your heartstrings to learn that these kids, who already go through so much, lose the chance to get new lungs because of a microbe.” Having gone into microbiology to make an impact on human health, Dr. Stallings welcomed the study of Mabs to her lab. “The techniques we use to study tuberculosis easily translate to Mabs. We are definitely able to apply what works well with TB to this other bacterium.” Part of the reason why bacterial infections are so difficult to treat is that, as a group, they can form their own protective armor, known as biofilm. Proving there truly is safety in numbers, this group or community of bacteria can produce different kinds of proteins that strengthen the group’s defense against antibiotics. Dr. Stallings’ lab has cultivated mycobacterial biofilm in culture to test compounds for their ability to break down this defense. They have found some that do just that. These mycobacterial biofilm inhibitors (MBIs) are the first examples of chemicals that effectively and specifically attack biofilm formation in mycobacteria, suggesting to Dr. Stallings’ vulnerabilities that have not yet been exploited by current treatments. “Without the support of the CDI, we would not have been able to discover that treatment of bacterial infections with MBIs increases the sensitivity of the bacteria,” Dr. Stallings says. “It has definitely broadened our understanding of how to fight these harmful organisms.”


Christina Stallings, PhD, molecular microbiology, leads her lab in finding better treatments for lung infections.

Mycobacterium abscessus (Mabs) is often referred to as an antibiotic nightmare.

Dr. Stallings is one of 11 CDI primary investigators currently studying lung diseases in children.

Factors that predispose cystic fibrosis patients to infection by Mabs remain unknown.

bright future

Karter, age 14 Like many 14-year-old boys, Karter loves to play baseball, basketball, and yes, video games. The fact that he has cystic fibrosis hasn’t kept him from second base or spending time with friends. “He’s a remarkable kid,” says Thomas Ferkol, MD, the Alexis Hartmann Professor of Pediatrics, and Karter’s pulmonologist since birth. “The way he and his family keep up with the treatments that come with a cystic fibrosis diagnosis while carrying on a normal, active life is truly commendable, given its high treatment burden.” The good news about cystic fibrosis is that our patients are living longer. But, Dr. Ferkol adds, with longevity comes treatment fatigue. “We’ve had to have some difficult conversations with patients, who somewhere in their teens or young adulthood conclude that they don’t need treatments anymore.” But cystic fibrosis is an insidiously progressive lung disease with no cure. Children born with it come into the world with normal lungs. Then, early on, the disease’s characteristic thick, sticky mucus renders the lungs susceptible to infection. Once infected, the lungs become inflamed. When the inflammatory cells produced to fight the infection die, they release enzymes and oxidants in the lungs that, over time, weaken the airways. Damaged airways produce more mucus, which attract more microbes that cause more infection. So far, Karter has avoided this vicious cycle by sticking with the regimen instilled in him by his parents, Kelly and Brent, his whole life. It involves inhaled medications and enzymes and a percussion vest he wears for 20 to 25 minutes three times a day to shear mucus off the surface of his airways. He works all this in while just being a normal kid, and then shrugs like it’s no biggie when asked about it. “Since we started all this when he was so young, it’s just a part of life. It simply doesn’t get in his way,” Kelly says. Karter stays on the playing field using the discipline he had to learn to keep his cystic fibrosis at bay.


More Bright Futures

Anne, age 4 Anne always lives life to the fullest. She loves to run, explore and ask questions. A little more than a year ago, she was diagnosed with acute lymphoblastic leukemia (ALL). Because she is in a “very high risk” category for potential relapses, her medical team laid out an intense regimen involving one year of chemotherapy, which she completed in late August of 2014, to be followed by another 18 months of maintenance therapy. With her on this journey is her grandmother, who is fighting acute myelogenous leukemia (AML). The two chat about their ports and IV lines the way war veterans reminisce about a battle. Anne’s little body is fighting hard to recover enough from her treatments to be able to begin pre-K, where she can focus on what kids her age should be focused on: learning, art, music and making friends.

Anne is fighting hard to get to pre-K and beyond leukemia.

“Her grace and strength inspire me daily,” says her mom, Sarah. “We know, with the help of her medical team who have become part of our family, she will overcome the cancer and live a long and beautiful life.”

Cassidy, age 12 Before she reached double-digits in age, Cassidy beat cancer, suffered chemo-induced lung disease, fought her way through two lung transplants and raised $30,000 to create an endowment for pediatric pulmonary research and family support. And she’s just getting started. Cassidy intends to employ her artistic talent, her entrepreneurial spirit and a winning smile to keep raising research dollars until no child has to endure lung transplant rejection. She has enlisted her friends to decorate and sell pencils and create colorful rainbow loom bracelets that replenish the inventory of Blue Moon Active Wear, a shop in Clayton, Missouri, where Cassidy was invited to sell her items. She and her friends also have become veterans at running lemonade stands, spreading the word with every glass they serve. “I know I like making crafts and bracelets so I thought I could sell them and donate the money to lung transplant research,” Cassidy says. “I’m so happy that people want to help me and grateful for their generous donations.”

Cassidy’s new lungs inspire her to help other kids.


Cassidy started the sixth grade this fall in her hometown of Franklin Lakes, N.J. And it’s safe to say that she’s the only one of her classmates to have created a charitable endowment. “When we had to stay in St. Louis for long periods of time, we had the resources to be able to stay there as a family,” says Cassidy’s mom, Kim. “Cassidy recognized that not all families can do that. That’s why, in addition to pulmonary research, a portion of the money raised through the Cassidy’s Creations endowment will go toward supporting families. She’s a strong, amazing little girl.”

2014 Research Success Stories

Bright minds, bold ideas are changing pediatric healthcare CDI investigators kept the Washington University School of Medicine public affairs office busy this year, reporting on their wide-ranging successes. Here are excerpts from those articles. To read the full story on these discoveries, visit childrensdiscovery.org. Preemies’ Gut Bacteria May Depend More on Gestational Age than Environment

Soil Bacteria May Provide Clues to Curbing Antibiotic Resistance

Proceedings of the National Academy of Sciences, August 11, 2014

Nature, May 21, 2014

Phillip Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics; and Barbara Warner, MD, pediatrics, have found that the population of bacteria in babies’ gastrointestinal tracts may depend more on their biological makeup and gestational age at birth than on environmental factors. The foundational work for this, the latest of this team’s insights into the microbiome of newborns, was laid with funding from the CDI.

New Culprit Identified in Metabolic Syndrome Nature Communications, August 7, 2014 Excess uric acid, a normal waste product the body removes through the kidneys and intestines, may play a direct causative role in metabolic syndrome. A study by CDI investigator Brian DeBosch, MD, PhD, pediatrics, shows that the gut is an important clearance mechanism for uric acid, opening the door to new potential therapies for preventing or treating type 2 diabetes and metabolic syndrome.

One Route to Malaria Drug Resistance Found Nature Communications, July 24, 2014 CDI investigator Audrey Odom, MD, PhD, pediatrics and molecular microbiology, and her colleagues have found one way the malaria parasite becomes resistant to fosmidomycin, an antimalarial drug in clinical trials. Using next-generation sequencing technology, the research team compared the genetics of malaria parasites that responded to the drug to the genetics of those that were resistant to it. With this approach, Odom and her colleagues found mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

Severe Scoliosis Linked to Rare Mutations Human Molecular Genetics, May 29, 2014 Children with rare mutations in two genes are about four times more likely to develop severe scoliosis than their peers with normal versions of the genes, scientists have found. Christina Gurnett, MD, PhD, neurology, has identified genetic risk factors that predispose children to develop S-shaped curves in their spines that are dramatic enough to require surgery.

Annually, drug-resistant bacteria sicken two million Americans and kill at least 23,000. A driving force behind this growing public health threat is the ability of bacteria to share genes that provide antibiotic resistance. A new study by CDI investigator Gautam Dantas, PhD, pathology and immunology, and his collaborators identified that bacteria that naturally live in the soil have a vast collection of genes to fight off antibiotics, but they are much less likely to share these genes. The findings suggest that most genes from soil bacteria are not poised to contribute to antibiotic resistance in infectious bacteria.

Gut Bacteria Can Cause Life-Threatening Infections in Pre-Term Babies Clinical Infectious Diseases, March 19, 2014 Babies born prematurely are surviving in increasing numbers, but many withstand complications of early birth only to suffer late-onset sepsis — life-threatening bloodstream infections that strike after infants reach 72 hours of age. The causes of late-onset sepsis have not been clear. But now, research led by Phillip Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics; and Barbara Warner, MD, pediatrics, discovered that pre-term babies’ guts harbor infectious microbes that can cause this condition.

Infants With Leukemia Inherit Susceptibility Leukemia, January 10, 2014 Babies who develop leukemia during the first year of life appear to have inherited an unfortunate combination of genetic variations that may make the infants highly susceptible to the disease, according to a new study led by CDI researcher Todd Druley, MD, PhD, pediatrics. Doctors have long sought to understand why babies just a few months old sometimes develop cancer. As infants, they have not lived long enough to accumulate a critical number of cancer-causing mutations.


2014 Research Overview

Launching new discoveries for the future Here are the new research projects that took shape in 2014.

Brian DeBosch, MD, PhD, pediatrics Faculty Scholar Award Dr. DeBosch will use his CDI funding to look for new therapeutic measures or lifestyle interventions to treat or prevent type 2 diabetes and pre-diabetes in children. He will focus his research on enterocytes, cells lining the gastrointestinal tract and their role in metabolism and controlling levels of uric acid. If not regulated properly, enterocytes and uric acid may cause childhood pre-diabetes.

Vikas Dharnidharka, MD, MPH, pediatrics Investigator Initiated Award Next-generation sequencing technologies will enable Dr. Dharnidharka and his collaborators to expand understanding of post-transplant lymphoproliferative disorder (PTLD). This malignant transformation of white blood cells can occur in recipients of solid-organ or tissue transplants and may lead to death. While many cases of PTLD are caused by the Epstein-Barr virus, others have no known cause. Dr. Dharnidharka hopes to identify other viruses involved in PTLD, as well as to identify Epstein-Barr genome sequences associated with poorer outcomes.

Todd Druley, MD, PhD, pediatrics Investigator Initiated Award Dr. Druley is continuing his investigation of the genomics of infant leukemia, looking for inherited genetic variation influences. Through this work, Dr. Druley seeks more effective treatments, as well as new strategies for engineering blood stem cells that could be transplanted into leukemia patients, ultimately improving their chance of survival.


Susan Dutcher, PhD, genetics Steven Brody, MD, medicine Investigator Initiated Award With each breath, human lungs are exposed to inhaled pollutants. Cilia are specialized hair-like structures that rely on hundreds of different proteins, including dynein motors, to sweep the lungs clean in a coordinated fashion. Ciliary dysfunction is known or suspected in a number of genetic and acquired disorders called ciliopathies, including primary ciliary dyskinesia (PCD), heart malformations and other birth defects. The goal of this project is to discover new genetic mutations involved in cilia-related human disease by studying patients with known PCD, and model the genetic defects in algae and zebrafish to understand how various factors assemble dynein motors to allow cilia to function.

Nicole Gilbert, PhD, molecular microbiology Postdoctoral Fellowship Award The Group B Streptococcus (GBS) bacterium, a major cause of life-threatening infection and lung damage in newborns, can colonize the vagina of the mother and invade the uterus during pregnancy, infecting both mother and baby. This can lead to pre-term delivery, fetal lung damage, pneumonia and other serious conditions. Dr. Gilbert, a post-doctoral fellow, and her collaborators are using their CDI award to investigate the interaction between GBS and a related condition called bacterial vaginosis, which is caused by a disruption in the balance of vaginal bacteria. Women with both conditions present are more likely than others to deliver pre-term babies who are at greater risk of lung damage.

Amanda Lewis, PhD, molecular microbiology Warren Lewis, PhD, medicine Interdisciplinary Research Initiative Award

Scott Saunders, MD, PhD, pediatrics

This research team is investigating if a certain enzyme found in the reproductive system can be a reliable biomarker indicating that a woman is at risk for pre-term labor and delivery.

David Ornitz, MD, PhD, developmental biology Brad Warner, MD, surgery Interdisciplinary Research Initiative Award

Jeffrey Magee, MD, PhD, pediatrics Faculty Scholar Award Dr. Magee studies bone marrow stem cells and how they behave differently in newborns compared to adults. By studying the relationship between stem cell regulation and leukemia growth at different ages, he hopes to identify age-specific mechanisms of how leukemia develops and new therapies to treat them.

Short bowel syndrome, a condition in which a large part of the small intestine is missing, is the focus of an investigation by these multidisciplinary collaborators. They will investigate if signaling pathways that regulate the growth of the small intestine during development can accelerate intestinal growth after birth. Their goal is to find new approaches to treat short bowel syndrome in children.

Lilianna Solnica-Krezel, PhD, developmental biology

Celeste Morley, MD, PhD, pediatrics

Jeffrey Milbrandt, MD, PhD, genetics

Interdisciplinary Research Initiative Award Dr. Morley is working to define the genetic factors that regulate immune response in order to develop new therapies for severe pneumococcal disease and other pediatric lung disease.

Audrey Odom, MD, PhD, pediatrics Baranidharan Raman, PhD, MS, biomedical engineering Interdisciplinary Research Initiative Award Continuing her work in malaria, a parasitic disease that claims the lives of hundreds of thousands of children each year, Dr. Odom teams up with Dr. Raman to develop and validate the use of a non-invasive device that detects malaria biomarkers in exhaled breath. Development of an inexpensive diagnostic tool will improve care of infected children and conserve antimalarial medications for children most in need.

Indi Trehan, MD, MPH, DTM&H, pediatrics Faculty Scholar Award Dr. Trehan will use his CDI funding to study whether including nutrient-rich legumes in the diet of rural Malawian children can improve their growth and health, and reduce signs of environmental enteropathy by promoting a healthy gut microbiome, meaning one that harbors more helpful rather than harmful bacteria.

Core Large Initiative Award Human pluripotent stem cells (hPSCs) have the potential to develop into all tissues of the body, offering great promise for discovering new treatments for birth defects, injuries and degenerative disease. They also enable researchers to create animal models of congenital childhood disease, as well as allow for the study of how embryos develop. To advance research using these cells, Dr. Solnica-Krezel and Dr. Milbrandt will use their CDI funding to create a human pluripotent stem cell and genome engineering core. This core will enable new projects and enhance existing CDI projects that use human pluripotent stem cells to study and develop new treatments for childhood diseases.

Thaddeus Stappenbeck, MD, PhD, pathology and immunology Steven Brody, MD, medicine Investigator Initiated Award This research will provide a valuable tool for lung stem cell studies, provide opportunities to investigate the mechanisms of childhood lung diseases, enable future drug testing on cells relevant to these diseases and pave the way for personalized therapies.


The Search Continues



Carlos Bernal-Mizrachi, MD, medicine Developmental Origins of Metabolic Syndrome and Cardiovascular Disease

Grant Challen, PhD, medicine Altered Epigenetics as a Driver of T-cell Acute Lymphoblastic Leukemia

Patrick Jay MD, PhD, pediatrics Solving Complex Congenital Heart Disease

Vikas Dharnidharka, MD, MPH, pediatrics Next-generation Deep Sequencing in Post-transplant Lymphoproliferative Disorders

Patrick Jay, MD, PhD, pediatrics; Gary Patti, PhD, chemistry A Modifiable Pathway to Prevent Congenital Heart Disease Beth Kozel, MD, PhD, pediatrics Genetic Modifiers of Elastin Insufficiency Jeanne Nerbonne, PhD, medicine Translational Cardiovascular Tissue Core Michael Shoykhet, MD, PhD, pediatrics Survival Strategies in Pediatric Cardiac Arrest Jennifer Silva, MD, pediatrics The Prospective Pediatric Cardiac Resynchronization Therapy Registry Christopher Smyser, MD, neurology Neuroimaging in Infants with Congenital Heart Disease and Relation to Neurodevelopmental Outcome


Todd Druley, MD, PhD, pediatrics Functional Characterization of Rare Congenital Variation in Infantile Leukemia; High Throughput Rare Variant Detection in High-Risk Pediatric Acute Lymphoblastomas

CENTER FOR MUSCULOSKELETAL AND METABOLIC DISEASES Ying Chen, MD, PhD, medicine Podocyte Endoplasmic Reticulum Stress in Hereditary Nephrotic Syndromes Megan Cooper, MD, PhD, pediatrics Innate Immune Memory; Investigation of Somatic Defects in Patients with Autoimmune Diseases Peter Crawford, MD, PhD, medicine Integration of the Ketogenic-ketolytic Axis with Metabolic Homeostasis in Newborn Period and Beyond

Jeffrey Magee, MD, PhD, pediatrics Developmental Changes in Stem Cell Self-renewal Mechanisms and Their Role in Leukemogenesis

Gautam Dantas, PhD, pathology and immunology Functional Characterization of Antibiotic Resistance Reservoirs in Developing Pediatric Microbiomes

Joshua Rubin, MD, PhD, pediatrics; David Gutmann, MD, PhD, neurology Sexually Dimorphic cAMP Signaling Impacts the Rate of Brain Tumors in Prepubertal Boys and Girls

Brian DeBosch, MD, PhD, pediatrics Role of Enterocyte Glut9 in Intestinal Urate Handling and Energy Homeostasis

Laura Schuettpelz, MD, PhD, pediatrics Elucidating the Role of KLF7 in T-cell Development Jason Weber, PhD, medicine Targeting Nucleolar Protein Interactions in Pediatric Gliomas

Joseph Dougherty, PhD, genetics; Joshua Maurer, PhD, chemistry Building Tools for Regenerative Medicine to Specify and Pattern Pluripotent Neural Crest Cells Stephanie Fritz, MD, pediatrics Epidemiology and Prevention of Staphylococcal Colonization, Infection and Transmission

Matthew Goldsmith, MD, pediatrics; Christina Gurnett, MD, PhD, neurology Genetic Studies of Scoliosis Etiology in Humans and Zebrafish Lori Holtz, MD, pediatrics Defining the Role of Viruses in Environmental Enteropathy Paul Hruz, MD, PhD, pediatrics; Katherine Henzler-Wildman, PhD, biochemistry and molecular biophysics Solution-State NMR Structure and Dynamics of Facilitative Glucose Transport Proteins Megan Killian, PhD, orthopedic surgery The Role of Scleraxis on the Development of the Tendon and Its Attachment to Bone Mark Manary, MD, pediatrics Understanding and Ameliorating Environmental Enteropathy Celeste Morley, MD, PhD, pediatrics Cytoskeletal Regulation of Immune Function Audrey Odom, MD, PhD, pediatrics; Baranidharan Raman, PhD, MS, biomedical engineering Toward Noninvasive Diagnosis of Malaria Infection Through Exhaled Breath Analysis Scott Saunders, MD, PhD, pediatrics; David Ornitz, MD, PhD, developmental biology; Brad Warner, MD, surgery Growth Factor Signaling Pathways Regulating Development of the Small Intestine Indi Trehan, MD, MPH, DTM&H, pediatrics Innovative Interventions for Improving Childhood Growth and Environmental Enteropathy

CENTER FOR PEDIATRIC PULMONARY DISEASE Gaya Amarasinghe, PhD, pathology and immunology Characterization of Structurebased Targets for Vaccines Against Respiratory Syncytial Virus Susan Dutcher, PhD, genetics; Steven Brody, MD, medicine Novel Approaches for Understanding Ciliary Assembly in Rare Childhood Diseases Nicole Gilbert, PhD, molecular microbiology Probing Bacterial Vaginosis Sialidase as a Risk Factor for GBS Colonization and Fetal Transmission Amjad Horani, MD, pediatrics Characterization of HEAT2 in Ciliogenesis Amanda Lewis, PhD, molecular microbiology; Warren Lewis, PhD, medicine GBS Hyaluronidase as a Determinant of Invasion and an Indication of Risk for Invasive Disease

MULTI-CENTER GRANTS Todd Druley, MD, PhD, pediatrics (and Robi Mitra, PhD, genetics) Accelerating Novel Genetic Discoveries by CDI Investigators Via Next-generation DNA Sequencing Bradley Evanoff, MD, medicine Research Forum — Child Health Kathryn Miller, PhD, biology CDI Summer Undergraduate Research Fellowship Program Kelle Moley, MD, obstetrics and gynecology Women and Infants’ Health Specimen Consortium Lilianna Solnica-Krezel, PhD, developmental biology; Jeff Milbrandt, MD, PhD, genetics, pathology and immunology Human Pluripotent Stem Cell Core For a complete description of current and completed research projects, please visit ChildrensDiscovery.org and select the Research Center of interest.

Celeste Morley, MD, PhD pediatrics Defining Host Determinants of Severe Childhood Pneumococcal Pneumonia Christina Stallings, PhD, molecular microbiology Novel Treatments for Mycobacterial Infections in Infants and Children Thaddeus Stappenbeck, MD, PhD, pathology and immunology; Steven Brody, MD, medicine Isolation, Expansion and Characterization of Lung Epithelial Stem Cells

Barbara Warner, MD, pediatrics The St. Louis Neonatal Gut Microbiome Initiative D.J. with his pediatric oncologist, Dr. Fred Huang


By the Numbers

Financial highlights $40.5 million invested in research to date

$163 million extramural grant funding obtained as a result of CDI awards

128 research grants awarded since inception

461 published research papers from Children’s Discovery Institute investigators

Center Award Totals 2006 – 2014 Congenital Heart Disease Center

Center for Musculoskeletal and Metabolic Disease

Multiple Centers




Center for Pediatric Pulmonary Disease

McDonnell Pediatric Cancer Center

Total Research Grants




Departments of Primary Investigators (2006 – 2014)* Biology – 5 Chemistry – 1 Biomedical Engineering – 1 Computer Science and Engineering – 1 Mechanical, Aerospace and Structural Engineering – 1 Cell Biology and Physiology – 3 Developmental Biology – 4 Genetics – 7 *Note: This chart does not include the many collaborators, across additional departments, who take part in research grants but aren’t the principal recipients of grants.


Medicine – 17 Molecular Microbiology – 5 Neurology – 4 Neurosurgery – 2 Obstetrics and Gynecology – 3 Orthopedic Surgery – 5 Pathology and Immunology – 10 Pediatrics – 59

Children’s Discovery Institute Leadership

Board of Managers Andrew E. Newman CHAIR

Richard J. Mahoney

Chairman, Hackett Security, Inc.

Retired Chairman and CEO, Monsanto Company

Dale L. Cammon Chairman and Co-CEO, Bryant Group, Inc.

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

Lee F. Fetter (Ex-Officio)

James S. McDonnell III

Group President, BJC HealthCare President, St. Louis Children’s Hospital Foundation

Retired Corporate Vice President, McDonnell Douglas Corporation

Daniel Getman, PhD

Charles W. Mueller

Retired President, Kansas City Area Life Sciences Institute

Retired Chairman and CEO, Ameren Corporation

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

Alan L. Schwartz, PhD, MD Executive Director, Children’s Discovery Institute Chairman of the Department of Pediatrics

Jeffrey I. Gordon, MD Dr. Robert J. Glaser Distinguished University Professor Director, Center for Genome Sciences and Systems Biology, Washington University School of Medicine Keith S. Harbison President and CEO, Capital Alignment Partners Jennifer Lodge, PhD Professor, Molecular Microbiology, Associate Dean for Research, Vice Chancellor for Research, Washington University in St. Louis

The Harriet B. Spoehrer Professor of Pediatrics Washington University School of Medicine Pediatrician-in-Chief, St. Louis Children’s Hospital Larry J. Shapiro, MD (Ex-officio) Executive Vice Chancellor for Medical Affairs and Dean, Washington University School of Medicine Raymond R. Van de Riet, Jr. Chief Administrative Officer, Aero Charter, Inc. Kelvin R. Westbrook President and Chief Executive Officer, KRW Advisors, LLC




St. Louis Children’s Hospital Foundation One Children’s Place, 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. We are entirely donor funded. And, for that, we say thank you. LEARN MORE AT CHILDRENSDISCOVERY.ORG

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Children's Discovery Institute / Investor Report 2014  

Every child treated at St. Louis Children’s Hospital inspires our clinicians and researchers to collaborate, to ask why, to inquire what can...

Children's Discovery Institute / Investor Report 2014  

Every child treated at St. Louis Children’s Hospital inspires our clinicians and researchers to collaborate, to ask why, to inquire what can...