A N U P D AT E F O R PA R T N E R S O F T H E C H I L D R E N ' S D I S C O V E R Y I N S T I T U T E S P R I N G 2 0 1 3

ChildrensDiscovery.org

IMPROVING PREGNANCY-RELATED HEALTH OUTCOMESA unique initiative provides samples and data for studies on women’s reproductive health and pediatric diseases ›

Three years ago, the Children’s Discovery Institute launched a one-of-a-kind initiative called the Women and Infants’ Health Specimen Consortium (WIHSC). Its aim is to track long-term, pregnancy-related health outcomes of women and their infants by collecting, processing and storing clinical samples taken from women before and during pregnancy, as well as samples from infants after delivery.

In addition to the samples, a comprehensive database of clinical outcomes from the WIHSC is available to the Washington University research community to study women’s reproductive health and pediatric diseases.

“The WIHSC is the only large tissue and biomedical information database in the United States that collects samples from women at different time points—during conception, throughout pregnancy and beyond,” says lead investigator Kelle Moley, MD, the James P. Crane Professor of Obstetrics and Gynecology at Washington University School of Medicine. “This consortium enables studies that probably weren’t possible before because we didn’t have access to these samples.”

By providing a vast resource of blood, urine, amniotic fluid and placenta tissue samples, as well as infant brain development data, the WIHSC can help scientists pinpoint factors that cause premature birth, such as high blood pressure in pregnant women, poor fetal growth, fetal chromosomal abnormalities, congenital heart disease, miscarriage, infertility and poor outcomes related to assisted reproductive technology. Ultimately, this research can lead to new diagnostic tools and treatment strategies for a range of pregnancy-related health conditions.

“The possibilities are endless,” Dr. Moley says. “This resource could help us develop predictors for pregnancy outcomes such as preterm birth, or understand the

fetal origins of adult diseases.” For this project, Dr. Moley is collaborating with Ann Gronowski, PhD, professor of pathology and immunology at the School of Medicine, and Marwan Shinawi, MD, associate professor of pediatrics at the School of Medicine.

Having recently expanded from recruiting patients and obtaining samples at one clinic to four centers, the WIHSC has enrolled more than 2,500 patients, including 500 infants, and banked more than 15,000 specimens. The consortium also has supported 16 research studies across eight departments, leading to the funding of nine additional federal and non-federal grants, totaling more than $3 million, and five published papers in leading journals. These studies have shown that certain harmful bacteria in the placenta are associated with adverse pregnancy outcomes. They’ve also demonstrated that elevated levels of compounds called free fatty acids are associated with poor quality

egg cells and a decreased chance of pregnancy in women undergoing in vitro fertilization.

Moving forward, the consortium will continue to expand its services to additional delivery hospitals and launch a monthly seminar series to increase awareness of this rapidly growing core facility.

“Typically, the National Institutes of Health and other funding agencies won’t fund infrastructure projects or projects that help support other projects. So we were very lucky to get support from the Children’s Discovery Institute,” Dr. Moley says. “Gestation is such an important period in a child’s development, yet it is often difficult to study across a nine-month period. We hope this consortium will provide the tissue and material needed to answer the most important questions in obstetrics, gynecology and early pediatric health.” ›

Lead investigator Kelle Moley, MD, oversees the Women and Infants’ Health Specimen Consortium (WIHSC), a new resource available for the study of women’s reproductive health and pediatric disease.

Recent Studies Showcase Wide-Ranging Research AdvancesAs the Children’s Discovery Institute embarks on its seventh year of funding innovative research to promote children’s health, I am continually impressed by the far-reaching accomplishments of the Institute’s talented investigators. Here are just a few of the recent published studies that deserve mentioning.

Two of these studies, published in Science and Nature, highlight the importance of sequencing the genomes of microbial communities to understand their impact on human health. For example, Gautam Dantas, PhD, and his team revealed that bacteria found in soil could transfer genes that cause antibiotic resistance to pathogens responsible for pneumonia and other life-threatening infections, making these conditions more difficult to treat. On the other hand, Barbara Warner, MD, and her collaborators showed that microbial communities in the intestinal tract vary significantly between people in different countries. This could explain how cultural factors such as diet could lead to different health outcomes across geographic locations.

As reported in Nature and Cancer Research, Joshua Rubin, MD, PhD, Jeffrey Leonard, MD, and their collaborators are making substantial progress in understanding medulloblastoma, the most common malignant brain tumor in children. By characterizing unique molecular and genetic patterns in different subgroups of medulloblastoma patients, these researchers will pave the way for personalized treatment plans for specific types of patients.

Beyond improving therapeutic options for patients, it is crucial to develop new tools to improve the diagnosis of diseases. Toward that end, Charles Canter, MD, Samuel Wickline, MD, and colleagues developed a noninvasive imaging method for detecting transplant coronary artery disease — the main complication that limits long-term survival in pediatric heart transplant recipients. This approach, reported in the Journal of Heart and Lung Transplantation, will help clinicians decide on the best treatment options for these patients.

Taken together, these new research advances illustrate the important work that Institute investigators continue to pursue in order to treat, cure and ultimately prevent a wide range of childhood diseases.

Mary Dinauer, MD, PhD

Mary Dinauer, MD, PhD, is the Scientific Director of the Children’s Discovery Institute. She also is the Fred M. Saigh Distinguished Chair in Pediatric Research at St. Louis Children’s Hospital, and Professor in Pediatrics, Pathology and Immunology at Washington University School of Medicine.

Research Citations

Forsberg KJ, Reyes A, Wang B, Selleck EM, Somer MOA, Dantas G. The shared antibiotic resistome of soil bacteria and human pathogens. Science, Aug. 31, 2012.

Northcott PA, Shih DJ, Peacock J, Garzia L,…, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Lau LM, Van Meir EG,…, Pfister SM, Marra MA, Taylor MD. Subgroup-specific structural variation across 1,000 medulloblastoma genomes, www.ncbi.nlm.nih.gov/pubmed/22832581. Nature. 2012 Aug 2;488(7409):49-56. doi: 10.1038/nature11327.

Tanya Yatsunenko, Federico Rey, Mark Manary, Indi Trehan, Maria Gloria Dominguez-Bello, Robert N. Baldassano, Andrey P. Anokhin, Andrew C. Heath, Barbara Warner, Jens Reeder, Justin Kuczynski, Catherine Lozupon6, Christian Lauber, Jose Carlos Clemente, Dan Knights, Rob Knight, and Jeffrey I. Gordon. Human gut microbiome differentiation viewed across cultures, ages and families. Nature (London). 14 June 2012 486:(7402): 222-227 (doi:10.1038/nature11053)

Sengupta, R, Dubuc, A, Ward, S, Yang, L, Northcott, P, Woerner, BM, Kroll, K, Luo, J, Taylor, MD, Wechsler-Reya, RJ and Rubin, JB. CXCR4 activation defines a new subgroup of Sonic Hedgehog-driven Medulloblastoma, www.ncbi.nlm.nih.gov/pubmed/22052462. (2011) 2012 Cancer Research 72, 122-132

Madani MH, Canter CE, Balzer DT, Watkins MP, Wickline SA. http://www.ncbi.nlm.nih.gov/pubmed/22749830 Noninvasive detection of transplant coronary artery disease with contrast-enhanced cardiac MRI in pediatric cardiac transplants. J Heart Lung Transplant. 2012 Nov;31(11):1234-5.

2 |

The Children’s Discovery Institute’s Fifth Annual Symposium gave investors the opportunity to learn about research advances from a selection of Institute-funded projects.

Kicking off the first session, Beth Kozel, MD, PhD, discussed her research on genetic factors that influence the severity of vascular disease in patients with Williams syndrome. These patients are prone to high blood pressure and stiff blood vessels. She has used mice to model these vascular problems and identify several genes that modify the severity of vascular disease. She also has confirmed that variation in one of these genes influences the severity of high blood pressure and vascular stiffness. Her talk highlighted the importance of using both animal models and human studies to pinpoint the genetic causes of human diseases. Ultimately, the research could help doctors predict which children will develop life-threatening vascular disease, and use this information to develop more effective, individualized strategies for clinical interventions. After the presentation, Dr. Kozel showcased instruments used for her research, including a vascular probe and a machine that measures the skin’s elasticity.

Armed with a container of brain tumor samples, the second presenter, Joshua Rubin, MD, PhD, discussed his research on factors that affect the risk of developing pediatric brain tumors. Boys have a higher rate of brain tumors than girls. To try to understand why, Dr. Rubin is studying brain tumors associated with neurofibromatosis 1 (NF1) — the most common genetic disease associated

HIGHLIGHTS OF THE FIFTH ANNUAL INVESTOR SYMPOSIUMSymposium provides hands-on opportunities to learn about research sponsored by the Children’s Discovery Institute

FROM THE SCIENTIFIC DIRECTOR Investor Engagement ›

Symposium participants peer through a microscope to get a better understanding of the genetic connection between humans and zebrafish. Yes, zebrafish.

with childhood brain tumors. Using a mouse model of NF1-associated brain tumors, Dr. Rubin has found that a molecule called cyclic AMP, which is important for the development of brain tumors, is regulated in different ways in the brain cells of males versus females. In humans, Dr. Rubin has found that genetic variations regulating cyclic AMP levels can account for gender differences in the risk of developing brain tumors. Moving forward, it will be possible to develop a screening tool to identify patients at risk for brain cancer prior to the onset of symptoms, and use this information to personalize clinical care. Ultimately, this research could lead to new strategies to prevent and treat brain cancer.

In the next session, Steven Brody, MD, showcased lung samples while discussing the importance of using cultured airway epithelial cells to study childhood lung diseases, such as asthma, cystic fibrosis and respiratory virus infection. The Airway Epithelial Cell Core provides Institute investigators with complex preparations of cells taken from the respiratory tracts of mice and humans; a repository of normal and diseased lung tissue; and technical training in methods for generating, maintaining and analyzing these high-quality cell preparations. This state-of-the-art resource enables researchers to better understand lung biology and develop new therapeutic strategies for diseases.

Christina Gurnett, MD, PhD; Matthew Goldsmith, MD; and Ryan Gray, PhD, presented their research on the genetic basis of scoliosis. They explained the advantages of using zebrafish—which were on display for investors to see—as an animal model for this condition. These tropical fish can develop curves in the spine, just like humans, and the genes involved in their development are similar to

those found in humans. By introducing mutations randomly into the zebrafish genome, the researchers have identified genes responsible for spinal curves. Moving forward, they will determine how these mutations cause spinal curves and will use these animals to screen for drugs that could correct the problem. They also have collected DNA samples from 500 patients with scoliosis and are performing gene sequencing to determine their genetic risk factors. Ultimately, their research could lead to the development of more effective diagnostic tools and preventive treatments. ›

Joshua Rubin, MD, PhD, lets investors get up close and personal with the brain tumors he uses in his research on factors that affect a child’s risk for developing these tumors.

Nicholas Yozamp, an assistant in Dr. Steven Brody’s lab, showcases lung samples used to study childhood lung disease.

…it will be possible

to develop a

screening tool to

identify patients at

risk for brain cancer

prior to the onset

of symptoms, and

use this information

to personalize

clinical care.

Investor Engagement ›

| 3

4 |

Investigator Spotlight ›

Faculty scholar awardee gets to the bottom of antibiotic-resistant Staph infections

It has long been known that methicillin-

resistant Staphylococcus aureus (MRSA)

— a type of Staph bacteria that is

resistant to treatment with many common

antibiotics — often takes up residence

in hospitals, putting hospital patients

at risk. But over the past 15 years, this

pathogen has found its way into people’s

homes as a new strain easily transmitted

from person to person. Nearly 2 percent

of individuals in the United States have

MRSA living in their noses or on their

skin (also known as colonization). This

can cause pneumonia and other serious

infections. MRSA also is the most

frequent cause of skin infections and

invasive, life-threatening infections

of the muscles and bones in children.

Community-associated MRSA can be curbed through good hygiene, covering cuts with bandages and washing sheets and towels in hot water. But effective methods for reducing MRSA colonization, interrupting the spread of MRSA and preventing infections are still lacking. “We have a lot of non-evidence-based recommendations that we give our patients to try to prevent recurrent infections, but we don’t know how well they work,” says Stephanie Fritz, MD, MSCI, assistant professor of pediatrics at Washington University School of Medicine. “We are trying to put the science behind the recommendations we make to our patients.”

With the help of a faculty scholar award from the Children’s Discovery Institute, Dr. Fritz is studying how MRSA spreads in the community, specifically within households, where infections tend to cluster. By following 150 pediatric patients with community-associated MRSA infection and their household contacts for one year, she is learning how family

members transmit MRSA to one another. Dr. Fritz samples household surfaces, such as countertops and television remote controls. She also surveys family members about places they visit that could expose them to the pathogen, as well as their hygiene practices, such as sharing towels.

“To date, studies have not been published which examine the transmission dynamics of Staph in the household, and right now people are very much at a loss for how to prevent these infections,” Dr. Fritz says.

“This study takes a thorough, whole-house approach to answer these questions. Our goal is to identify the environmental surfaces in the household that might be playing a key role in transmission. Then we’ll be able to focus our interventions on those targets and develop better preventive strategies.”

Dr. Fritz also will take DNA samples from these individuals and study the DNA of the germs they carry to determine which genetic factors increase susceptibility to MRSA and severe infections. For instance, differences in genes that regulate immune responses in individuals could affect their ability to fight infections, while genetic differences among Staph strains could influence their virulence. “Right now, we don’t have a vaccine to prevent Staph infections, and it’s not well known what the targets should be for a vaccine. The information we are assembling could help us develop a vaccine, and certainly could help us decide who should receive a vaccine,” Dr. Fritz says. “For example, knowing more about who is most susceptible to these invasive infections will help us decide who should be immunized and who should receive more aggressive therapy.”

Based on preliminary data collected through this Institute-funded project, Dr. Fritz has been awarded a $2.5 million grant from the U.S. Department of Health & Human Services’ Agency for Healthcare Research and Quality. “The Children’s Discovery Institute has been essential for allowing junior investigators to launch our research programs,” she says. “We often have very creative ideas that may not be mainstream enough for traditional funding agencies. Very fruitful, innovative and exciting research funded by the Institute really helps us provide the most up-to-date care for pediatric patients.” ›

UNDERSTANDING THE CAUSES OF COMMUNITY-ASSOCIATED INFECTIONS

“Our goal is to identify the environmental surfaces in the household that

might be playing a key role in transmission. Then we’ll be able to focus our

interventions on those targets and develop better preventive strategies.”

— Stephanie Fritz, MD, MSCI

What’s on your countertop? Stephanie Fritz, MD, displays a culture of Staphylococcus aureus – better known as MRSA – which may provide clues on how the infection spreads in households.

Featured Research ›

Determining the origins of metabolic syndrome could lead to healthier kids

Obesity is an epidemic among children and adolescents in the United States, and for the first time in centuries, it threatens to make their life expectancy shorter than that of their parents.

Nearly one in five children and adolescents are obese, putting them in danger of developing metabolic syndrome, a cluster of conditions that increases the risk for heart disease and other health problems, including diabetes and stroke. Children with metabolic syndrome have at least four risk factors: excessive belly fat, high blood pressure, high cholesterol and high blood sugar.

Factors that increase a child’s risk for obesity traditionally have been thought to be limited to lifestyle choices, such as diet and exercise. But this may not always be the case. Instead, obesity and its health complications also may stem from conditions in the womb.

“Metabolic syndrome is a major public health problem, but not many studies have focused on its origins,” says Carlos Bernal-Mizrachi, MD, assistant professor of medicine and cell biology and physiology at Washington University School of Medicine.

“The objective of my research is to try to identify environmental conditions or other factors in the womb that affect the development of metabolic syndrome.”

Dr. Bernal-Mizrachi focuses on vitamin D and its role in immune system function, which in turn influences the development of metabolic syndrome. Many pregnant women have vitamin D deficiency. These women often give birth to children who eventually become obese and develop metabolic syndrome.

“There are many trials indicating that vitamin D may be fundamental during pregnancy and the early postnatal period to prevent or ameliorate the development of metabolic disorders,” Dr. Bernal-Mizrachi says.

In past research, Dr. Bernal-Mizrachi has identified potential mechanisms by which vitamin D regulates immune cell responses and the development of cardiovascular disease. That has laid the groundwork for clinical trials assessing the benefits of vitamin D supplementation. He has recently discovered that vitamin D deficiency in mice causes an increase in blood pressure and hardening of the arteries and alters immune cell responses — patterns associated with metabolic syndrome.

With the support of the Children’s Discovery Institute, he is now turning his attention to the influence of vitamin D deficiency on the genetics of immune cells in the womb and how this contributes to the

development of metabolic syndrome after birth. So far, he has found that mice genetically engineered to lack the vitamin D receptor in immune cells have metabolic abnormalities resembling those caused by vitamin D deficiency in the womb. In collaboration with Washington University’s Ting Wang, PhD, assistant professor of genetics, and Mark Sands, PhD, professor of medicine, Dr. Bernal-Mizrachi is identifying specific genes and tissues that are affected by vitamin D deficiency during embryonic development. These genes and tissues could play a role in the development of metabolic syndrome. “Without the Children’s Discovery Institute, I would not have been capable of progressing in this research,” Dr. Bernal-Mizrachi says.

Through this interdisciplinary research initiative, Dr. Bernal-Mizrachi hopes to provide firm evidence for the importance of vitamin D supplementation during pregnancy and uncover potential targets for drugs that could prevent and treat obesity and metabolic syndrome, paving the way for clinical trials.

“These findings could potentially change the way we look at metabolic syndrome. There are major health implications, because there are potentially ways to resolve it,” he says. “One potential way is to improve vitamin D supplementation, but this may not be the whole story. If we can understand the environmental conditions that play a role early on, we can come up with other strategies for intervention.” ›

RESEARCH TACKLES OBESITY-RELATED HEALTH PROBLEMS IN CHILDREN

“There are many

trials indicating that

vitamin D may be

fundamental during

pregnancy and the early

postnatal period to

prevent or ameliorate

the development of

metabolic disorders.”

— Carlos Bernal-Mizrachi, MD

Carlos Bernal-Mizrachi, MD, hopes to provide evidence of the importance of vitamin D supplementation during pregnancy and uncover ways to prevent and treat obesity in children.

6 |

“These new research advances

illustrate the important work

that Institute investigators

continue to pursue in order

to treat, cure and ultimately

prevent a wide range of

childhood diseases.”

– Mary Dinauer, MD, PHD

The Children’s Discovery Institute’s newest Faculty Scholar, Lori Holtz, MD, is on the prowl for new viruses associated with disorders of the childhood digestive system. One such disorder, known as environmental enteropathy (EE), leads to malnutrition and stunted growth and contributes to one-third of childhood deaths worldwide. In her new translational research laboratory, Dr. Holtz will test the hypothesis that viruses are associated with the development of EE. The tools her lab develops for this undertaking will also be useful in the study of other diseases that have a yet-undefined viral cause. ›

Interdisciplinary Research Initiatives

Gaya Amarasinghe, PhD (Pathology/Immunology) Characterization of Structure-based Targets for Vaccines Against Respiratory Syncytial Virus. This project will work to move us closer to

vaccines that fight respiratory syncytial virus (RSV), a major cause of lung infections and breathing problems in children.

Grant Challen, PhD (Medicine) Altered Epigenetics as a Driver of T-cell Acute Lymphoblastic Leukemia. The long-term goal of this project is to help develop

treatments and improve outcomes for patients with acute lymphoblastic leukemia, the most common cancer in children.

Peter Crawford, MD, PhD (Medicine) Integration of the Ketogenic-ketolytic Axis with Metabolic Homeostasis in Newborn Period and Beyond. Up to 10 percent of newborns

aren’t fueled with the correct amount of blood sugar glucose. Undetected, this metabolic problem can contribute to neurological conditions and even sudden infant death syndrome. Dr. Crawford will investigate whether the presence of an alternate fuel source, called Ketone bodies, in newborns is the red flag needed to detect low blood sugar and its complications.

Robert Heuckeroth, MD, PhD (Pediatrics); Joseph Dougherty, PhD (Genetics and Psychiatry); and Joshua Maurer, PhD (Chemistry)

Building Tools for Regenerative Medicine to Specify and Pattern Pluripotent Neural Crest Cells. Birth defects are the most common

cause of infant death in the United States. We know that the failure of cells responsible for many critical structures in the body to divide, migrate or differentiate normally is the culprit. The goal of this research is to establish new ways to rebuild the circuitry that generates healthy tissue and organs.

Audrey McAlinden, PhD (Orthopedic Surgery)Identification of Novel and Differentially-expressed Non-coding RNAs During Human Limb Development. This is one year

of additional funding to follow up on promising leads from a study regarding the development of cartilage tissue. Knowledge gained may lead to novel ways to regenerate that tissue after damage from certain childhood diseases.

S. Celeste Morley, MD, PhD (Pediatrics) Defining Host Determinants of Severe Childhood Pneumococcal Pneumonia. Pneumonia caused by the bacteria Streptococcus

pneumoniae kills more than half a million children worldwide each year. In this study, Dr. Morley and her collaborators will use DNA samples from patients in databases from St. Louis and Papua New Guinea to identify genetic differences that predispose a child for this pneumonia.

Christina Stallings, PhD (Molecular Microbiology) Novel Treatments for Mycobacterial Infections in Infants and Children. Tuberculosis bacteria can be extremely difficult to treat due to their high

drug tolerance. Dr. Stallings and her collaborators are hoping to find novel drug therapies to treat tuberculosis in children.

Jason Weber, PhD (Medicine); Jeffrey Leonard, MD (Neurosurgery)

Targeting Nucleolar Protein Interactions in Pediatric Gliomas. Gliomas are one of the most common brain tumors in children. The

survival rate for patients with a high-grade form of these tumors is less than one year. This project will investigate the role of two proteins located in the brain — nucleolin (NCL) and nucleophosmin (NPM) — in the development of gliomas. This will help establish whether to target these proteins in the treatment of gliomas.

Fellowships

Amjad Horani, MD (Pediatrics) Characterization of Novel Primary Ciliary Dyskinesia Genes. Primary ciliary dyskinensia (PCD) is the paralysis of cilia. Without

movement, these these tiny hairs lining airways and nasal passages are unable to defend the respiratory system. Dr. Horani recently discovered that a mutation of a gene called HEATR2 affects multiple children with PCD in a large Amish-Mennonite family in Missouri. Further study will help identify novel ways to correct cilia function in a range of pulmonary diseases.

Megan Killian, PhD (Orthopedic Surgery) The Role of Scleraxis on the Development of the Tendon and Its Attachment to Bone. This project will provide insights into the

molecular mechanisms that regulate tendon-to-bone attachment and contribute to new treatments for birth-related defects that affect muscle movement. ›

ELEVEN NEW PROJECTS TAKE AIM AT CHILDHOOD ILLNESSThe Children’s Discovery Institute recently awarded more than $2.7 million to fund 11 new research proposals.

LORI HOLTZ, MD, NAMED FACULTY SCHOLAR

Funding Update ›

As a retired chief executive officer of a utility company and an original board member of the Children’s Discovery Institute, Chuck Mueller sees the value of a team-based approach to finding cures for pediatric diseases. That’s why he and his wife, Jan, are enthusiastic supporters of the Institute.

Q: How did you become involved in the Children’s Discovery Institute?

Chuck: My predecessor as chief executive officer of Union Electric was chairman of the St. Louis Children’s Hospital board. He got me involved. I’ve been on the hospital board for about 20 years. I was chairman for six years. I’ve been on the Foundation board for eight or 10 years, and I’ve been on the Children’s Discovery Institute board since its inception. I was co-chairman of the capital campaign that raised money for the Children’s Discovery Institute. I got interested in it when I heard it described and its goals of accelerating cures for kids, alleviating kids’ suffering and preventing diseases. It’s pretty easy to buy into.

Q: Why are you enthusiastic about supporting the Children’s Discovery Institute?

Chuck: First of all, I know St. Louis Children’s Hospital very well. Their motto is “do what’s right for kids,” and I’ve seen it in the hospital staff and administration. It’s a very efficient, competent and caring organization, and really the sponsor of the Children’s Discovery Institute. St. Louis Children’s Hospital has teamed up with Washington University, which is a top-notch research organization in the country. You just couldn’t duplicate that. It’s like a marriage made in heaven, and it’s pretty easy to get enthused about it.

Q: What makes the Children’s Discovery Institute unique among charitable organizations?

Chuck: It’s a research organization focused on pediatrics, which is very short of funding. The process at the Children’s Discovery Institute is very efficient. A scientific panel selects worthwhile causes. That panel stresses the work of young researchers. It’s seed money to get these young people started in research doing pediatric work and to set them up for grants from the National Institutes of Health. It’s a team-based approach. It’s not just the medical school at Washington University that’s involved. There are no silos. The Institute brings in the physics and chemistry departments and everyone else. Oversight

is provided by board representatives at St. Louis Children’s Hospital and Washington University. I think it’s a very worthwhile endeavor.

Q: Why do you consider the Children’s Discovery Institute a good investment?

Chuck: 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.

Chuck graduated from Saint Louis University with a bachelor’s degree in electrical engineering and an MBA. He started working for Union Electric Company (now Ameren) in 1961 and became the company’s chief executive officer in 1993. Retired for 10 years, he currently serves on the boards of St. Louis Children’s Hospital and the Municipal Theatre Association of St. Louis. His wife, Jan, was a legal assistant who later stayed at home to raise their three sons. Chuck and

Jan also have eight grandchildren and one great-grandson. ›

Chuck and Jan Mueller, Investors in the Children’s Discovery Institute ›

WHY I GIVE

Why do you give? Share your personal story with us. Contact Janice Bailey at jbailey@bjc.org.

| 7

Children’s Discovery Institute investors Charles and Jan Mueller received the Children’s Hospital Heart of Gold award in 2006.

“It’s seed money to get

these young people started

in research doing pediatric

work and to set them up for

grants from the National

Institutes of Health.“

– Chuck Mueller

8 |

I N S I D E T H I S I S S U E›

Improving Pregnancy-Related Health Outcomes ........................cover

Investor Symposium Highlights ..........................................page 2

New Faculty Scholar vs. Antibiotic Resistant Staph Infections ..page 4

Vitamin D’s Role in Childhood Obesity ...................................page 5

Why Chuck and Jan Mueller Invest in the Institute ...................page 6

A N U P D AT E F O R PA R T N E R S O F T H E C H I L D R E N ' S D I S C O V E R Y I N S T I T U T E

St. Louis Children’s Hospital FoundationOne Children’s Place St. Louis, MO 63110

If you have comments or questions about Pathways, please contact:This newsletter shares the accomplishments of the Children’s Discovery Institute with our stakeholders, particularly those whose generosity supports the research carried out by Institute investigators.

Janice BaileyVice President St. Louis Children’s Hospital Foundation

314.286.0971888.559.9699jbailey@bjc.org

Wednesday, November 13, 2013

6:30-8:30 p.m.Charles F. Knight Executive Education & Conference Center at the Washington University Danforth Campus

Meet Children’s Discovery Institute researchers and experience this interactive, hands-on event. Learn more about how your investments are accelerating discoveries for children.

Cocktails and hors d’oeuvres will be served.

Invitation coming this fall!

Children’s Discovery Institute ›

BOARD OF MANAGERSChair: Andrew E. Newman Chairman Hackett Security, Inc.

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

Lee F. Fetter (Ex-officio) Group President, BJC HealthCare President, St. Louis Children’s Hospital Foundation

Daniel Getman, PhD Retired President, Kansas City Area Life Sciences Institute Former Vice President, Pfizer R&D Director, St. Louis Laboratories

Jeffrey I. Gordon, MD Dr. Robert J. Glaser Distinguished University Professor Director, Center for Genome Sciences Washington University School of Medicine

Keith S. Harbison President and Chief Executive Officer Harbison Corporation

Jennifer Lodge, PhD Associate Dean for Research Professor of Molecular Microbiology Washington University School of Medicine

Richard J. Mahoney Retired Chairman and CEO, Monsanto Company Distinguished Executive in Residence at the Murray Weidenbaum Center on the Economy, Government and Public Policy, Washington University in St. Louis

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

Charles W. Mueller Retired Chairman and Chief Executive Officer Ameren Corporation

Alan L. Schwartz, MD, PhD Head of Department of Pediatrics, St. Louis Children’s Hospital Harriet B. Spoehrer Professor of Pediatrics, Washington University School of Medicine

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 Offier KRW Advisors, LLC

The Children’s Discovery Institute research focuses on four centers ›

Congenital Heart Disease Center

McDonnell Pediatric Cancer Center

Center for Pediatric Pulmonary Disease

Center for Musculoskeletal and Metabolic Diseases

PLEASE JOIN US!Mark your calendars! ›

Sixth Annual

Children’s Discovery Institute Symposium

› Visit our website for ongoing research updates and videos.

› ChildrensDiscovery.org