For over nearly a century, Children’s Hospital of Philadelphia has been home to one of the most vibrant and robust pediatric research institutions in the world. Our position as a leader in pediatric research underscores that innovation is both a differentiator for CHOP and critical to the Research Institute’s mission.

We’ve made myriad contributions to understanding the causes of pediatric diseases and conditions and developing new ways to treat patients and improve care every day. Whether in the laboratory or the clinic, the commitment, compassion, and vision of our investigators and their teams has unquestionably broadened the world of possibility for more children.

Amid our accomplishments, it’s good policy to periodically pause and assess where the organization has been and its future directions. During FY16 we engaged in an in-depth and extensive strategic planning process aimed at gaining a fresh perspective – one based on honest assessment, benchmarking, and insight from key stakeholders – to create a roadmap for the next stage in the evolution of the Research Institute.

The strategic planning initiative was, in essence, an opportunity to not only promote our tradition of excellence but to redefine what excellence means as we strive to create healthier futures for each generation.

Underlying this nearly yearlong initiative is the unwavering support of our preeminent community of researchers who together have the breadth and depth of scientific expertise to continue leading the world in basic scientific discovery and creating breakthroughs in care for all children. At the conclusion of the strategic planning process, we are devoted to cultivating an even higher-performing environment that mobilizes the right experts to solve the most challenging problems in child health.

The culture of the Research Institute will evolve into one that fosters “faculty-first” collaboration. This means we will fortify our infrastructure and channel our unique resources to build upon our research teams’ previous successes at CHOP and accelerate our progress to achieve greater pediatric research excellence from bench to bedside and beyond. We will accomplish this by implementing the following specific tactics:

• Strengthen our expertise in fundamental basic sciences to fuel scientific breakthroughs, leading to treatments/cures for rare diseases
• Develop pediatric-focused interventions and treatments to prevent onset of adult disease
• Understand how diseases progress into adulthood and optimize treatments to enhance function and improve lives as children become adults
• Develop novel therapies, medical devices, and treatment techniques that cure disease and reward innovation
• Lead the world in first-in-pediatrics clinical trials for new drugs and devices
• Create scientific capacity to address critical public/population health challenges and engage with the Philadelphia community and beyond
• Develop a first-of-its-kind multi-dimensional data collection, integration, storage, and analytic capability

As we reach our ambitious goals, the Research Institute’s efforts will truly redefine pediatric research excellence to advance scientific discovery at CHOP and improve the lives of children everywhere.

When Children’s Hospital of Philadelphia established the Center for Applied Genomics (CAG) in 2006 with a $40 million commitment, it was one of the largest single investments in a research program in the hospital’s history. The ambitious idea spearheaded by CAG’s founder and director, Hakon Hakonarson, MD, PhD, was to establish the world’s largest pediatric genomics biobank and to use that vast quantity of genetic data to discover the causes of disease and disability hidden within a population’s genes. A decade later, that ambition has translated to spectacular, world-leading successes thanks to hundreds of scientists’ intelligence and hard work and hundreds of thousands of families’ help.

The enormous collection of DNA samples, powered by family participation, is the lynchpin of that effort. From the earliest days after CAG was established, well over 100 CHOP investigators were eager to build this biobank. Together with members of the CAG staff, many of whom have been with the program since its inception, they have contributed to patient recruitment, phenotyping, and sample collections from families who volunteered to participate.

“This is by far the biggest pediatric biobank in the world,” said Dr. Hakonarson, who is also a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “No one has anything remotely close to what we have built here at CHOP.”

Today, the CHOP biobank includes samples from more than 400,000 people, including about 100,000 CHOP patients and their family members. With such a large number of samples, CHOP investigators have great statistical power to detect genetic variations underlying diseases in the population and to discover links between genetic underpinnings and disease phenotypes among patients. The biobank has contributed to discoveries that have been published in more than 500 scientific papers, many of them appearing in top-tier journals such as Nature and Cell. These encompass findings about the gene variations and genetic pathways involved in a wide range of conditions, including asthma, autism spectrum disorder, attention deficit hyperactivity disorder, cancers, schizophrenia, and Type 1 diabetes. In addition, CAG investigators and their collaborators have helped hundreds of families to resolve the underlying genetic causes of their extremely rare diseases.

More recently, CHOP researchers have begun to translate the collaborative genomic discoveries made with the CAG into novel therapies. For example, Yael Mossé, MD, a pediatric oncologist at CHOP and associate professor of Pediatrics at Penn, led a team that in 2008 discovered that a mutation in the gene ALK was a driver of most cases of rare, inherited neuroblastoma, a pediatric nervous system cancer. Within months after this discovery, neuroblastoma patients were able to receive an ALK-inhibitor drug, crizotinib, which had been approved for adults with lung cancer. Dr. Mossé and colleagues have continued to build on this work, identifying more effective ALK inhibitors to help patients whose tumors were less responsive to crizotinib. She is working to launch a clinical trial for a new drug.

A decade ago, success was by no means assured. But today, CAG’s influence is evident across the research landscape and is poised to grow as more of the center’s genomic discoveries lead to improved therapies and possibly cures for some of the most complex and devastating conditions affecting children.

Read more in a Bench to Bedside article.

Heart-stopping. Critical moment. Life-or-death. The catchphrases that define powerful dramatic scenes have real-life antecedents in pediatric intensive care units (PICUs), where sick children are at the highest risk of cardiac arrest in the hospital. After an arrest, more than half of children do not survive to hospital discharge, adding up to more than 3,000 deaths each year.

But a decades-long effort at Children’s Hospital of Philadelphia to make cardiopulmonary resuscitation (CPR) smarter has begun to tip that balance in favor of survival, locally, nationally, and internationally.

In recent years, a CHOP team has demonstrated an approach producing significant improvements in both CPR quality and patients’ survival — and patient survival with favorable neurological outcomes has doubled. CHOP is developing the nation’s first specialized pediatric cardiac arrest center, combining extraordinary clinical care, pioneering translational research, and global education and outreach.

“CHOP has led the field in discovering what is important for the quality of CPR for children, in the knowledge exchange and implementation science of how to perform and disseminate high quality CPR, and in modeling how CPR affects outcomes and quality of life for critically ill and injured children,” said Vinay Nadkarni, MD, MS, a critical care physician at CHOP and professor at the Perelman School of Medicine at the University of Pennsylvania. “Kids are not just little adults. We are getting closer to solving the challenges of figuring out the impact of age, size, and developmental life cycle on performance and outcomes of CPR.”

With a new grant from the National Institutes of Health awarded this spring, CHOP research scientists led by Robert Sutton, MD, MSCE, an attending critical care physician and assistant professor at the Perelman School of Medicine at the University of Pennsylvania, aim to disseminate CHOP’s success across eight hospitals in a national clinical trial. They are helping hospitals across the globe to replicate their bundled approach of bedside refresher training, resuscitation to physiologic blood pressure targets, and post-arrest debriefing using quantitative data (almost like instant replay in sports) for the entire unit to learn from and improve the process of care after each cardiac arrest.

This bundle’s effectiveness is the result of a combination of basic and translational investigation with bedside implementation of clinical therapies at CHOP over the past five years. The new emphasis on physiologic targets for CPR outcomes, for example, contrasts with older methods that focus only on the rate and depth of chest compressions. This innovation began with CHOP’s large animal studies in the lab of Critical Care Medicine Division Chief Robert Berg, MD, that led to providing this more personalized CPR approach to patients. This approach also included the development of specialized training manikins on rolling carts so that clinicians could practice the newer methods at the bedside on a frequent basis.

With the new NIH grant, they will test whether this successful bundled approach leads to similar improvements in outcomes at other children’s hospitals throughout the Collaborative Pediatric Critical Care Research Network (CPCCRN), a core group of eight top-tier medical centers with an intense focus on studying resuscitation improvement in pediatric ICUs. CPCCRN and other larger clinical research networks for resuscitation, such as the pediatric Resuscitation Collaborative (pedi-RES-Q) led by CHOP and supported by an unrestricted educational grant from the Zoll Corporation, extend the work CHOP does as the nation’s first specialized pediatric cardiac arrest center across the nation and the globe. The evidence-based methods that demonstrate success in these expanding concentric circles of research and quality improvement networks, in turn, shape the evidence and future guidelines for organizations such as the American Heart Association, which set the standard for how all hospitals respond to and treat cardiac arrest nationwide.

Read more in a Bench to Bedside article.

While many emerging diseases are scary, for many infectious disease specialists, antibiotic-resistant superbugs remain enemy number one. That is because these are the bugs that have learned how to evade our best defenses. Two million people in the U.S. become infected each year with organisms that are resistant to antibiotics, and those infections are the direct cause of at least 23,000 deaths annually, according to the Centers for Disease Control and Prevention (CDC). And, as more bugs are exposed to more drugs and evolve new tricks to elude them, the threat continues to grow.

Research on the best ways to keep antimicrobial medicines working as well as possible, for as long as possible, got a shot in the arm in June 2016 when the CDC announced $26 million in renewed funding for five of its Prevention Epicenters, more than doubling its previous awards and extending the program to 2020. The program brings together a small number of elite academic research centers, now 11 in total, to address problems in healthcare-associated infections.

The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania Epicenter site received more than $5 million to continue its work, now with an increased emphasis on pediatrics, in addition to adult patients. With the renewal, Jeffrey Gerber, MD, PhD, medical director of the antimicrobial stewardship program at CHOP and assistant professor of Pediatrics and Epidemiology at Penn, joined Ebbing Lautenbach, MD, MPH, MSCE, chief of the division of Infectious Diseases at Penn, as co-principal investigator for the Penn-CHOP site.

Innovation and improvement in antimicrobial stewardship — practices to ensure that the right drugs get to the right patients in the right dose and delivery — are a particular strength of the Penn-CHOP site.

“The idea is to find a way to preserve the effectiveness of these often curative and sometimes lifesaving drugs, but not to lose them,” Dr. Gerber said. “The overall goal is to optimize antimicrobial use, which is not just rationing or restriction, but designing systems to ensure that people select the drugs that work best to help fight infections while limiting unnecessary exposure that leads to antimicrobial resistance and adverse drug effects.”

The broad collaboration across CHOP and Penn capitalizes on investigators’ expertise in fields ranging from infectious diseases, critical care, pulmonary medicine, emergency medicine, epidemiology, biostatistics, bioinformatics, health economics, and microbiology. In addition to their emphasis on antimicrobial stewardship, they will focus on areas including risk factors and outcomes for healthcare-associated viral infections in hospitalized children and adults, and use of biomarkers to inform antimicrobial prescribing.

Read more about some of the CHOP-Penn Epicenter site’s unique strengths on the Cornerstone blog.