Established to speed research from the bench to the bedside, The Children’s Hospital of Philadelphia Research Institute’s Centers of Emphasis concentrate investigator efforts and resources. Bringing together many of the most pioneering researchers in the U.S., CHOP Research’s Centers of Emphasis have become well known for their consistently excellent, forward-thinking investigations.
During fiscal 2013 the Institute’s current Centers — which include the Center for Applied Genomics, the Center for Childhood Cancer Research, PolicyLab, and the Center for Injury Research and Prevention — were joined by a new Center of Emphasis, the Center for Clinical Pharmacology (CCP).
Led by Athena F. Zuppa, MD, MSCE, the CCP offers pharmacological training, bioanalytical and pharmacostatistical support, and study design services. By “restructuring and rebuilding” on previously existent resources, the new Center of Emphasis provides a single, consolidated resource for investigators across the Institute, according to Dr. Zuppa.
Dr. Zuppa joined CHOP in 1996 as an intern after receiving her medical degree from SUNY Stony Brook. She was named an assistant professor of Anesthesia and Pediatric Critical Care Medicine Pediatrics in 2002, and — in addition to her new role leading the CCP — is now an associate professor of Anesthesiology and Critical Care at the Hospital of the University of Pennsylvania and CHOP as well as associate director of Children’s Hospital’s PICU Fellowship Program. Dr. Zuppa has an active research program, and she is currently supported by a number of grants, including an R01 that is funding her investigation of the impact of hypothermia on the pharmacokinetics of midazolam (used for sedation) and the painkiller morphine (pain control) in children following cardiac arrest.
As Dr. Zuppa sees it, the CCP’s overarching structure will be supported by three pillars: training in clinical pharmacology, bioanalytical services, and pharmacostatistical support.
“If there are investigators who want to do a pharmacology study, they can come to us, and we can help them with study design, implementation, quantitative analysis of the biologic specimens, wrap that up into a database, and then actually interpret the data,” she said.
Dr. Zuppa also noted that along with Thomas Jefferson University, CHOP has applied for a T32 award to support a training program in clinical pharmacology. If approved, the joint CHOP-Thomas Jefferson training program would “be one, if not the first, pediatric and adult clinical pharmacology training programs bridging pediatrics and adults,” she said.
In addition to Dr. Zuppa, other CHOP staff who will be contributing to the CCP include Director of the Bioanalytical Core Ganesh Moorthy, PhD; pharmacometrician Chee Ng, PharmD, PhD; pediatric intensivist Adam S. Himebauch, MD; pediatric oncologist and Chair of the Children’s Oncology Group Peter C. Adamson, MD; director of clinical research in the Center for Childhood Cancer Research Frank M. Balis, MD; and pediatric oncologist and pharmacologist Elizabeth Fox, MD, head of the Developmental Therapeutics Program in the Division of Oncology. Dr. Zuppa noted that she is also actively looking to expand the new Center’s faculty and staff.
A trade mission to Israel led by Philadelphia Mayor Michael A. Nutter during fiscal 2013 led to a new research agreement between The Children’s Hospital of Philadelphia, Drexel University, and The Hebrew University of Jerusalem. The partnership — which is focused on pediatric translational research and moving investigations from the bench to the bedside — stimulated a January conference hosted by CHOP that gave researchers from all three institutions the chance to connect and share ideas.
“I am proud to see two great Philadelphia institutions, CHOP and Drexel University, expand their research overseas,” said Mayor Nutter when the agreement was signed in a ceremony at Jerusalem’s City Hall, Nov. 11, 2013.
Prior to the signing of the research agreement, Drexel University and Hebrew University already had a partnership in place, the Joint Drexel-Hebrew University Institute for Drug Research Hub. The new collaboration with CHOP will “address unmet needs in pediatrics through innovative commercial pediatric therapeutics and diagnostics,” said John A. Fry, president of Drexel University.
The collaborative research symposium, hosted by the Research Institute, brought together investigators from all three institutions for presentations and discussions aimed at fostering cooperation and teamwork. One of the goals of the symposium was to form collaborative “Dream Teams” of investigators who would unite to craft innovative solutions to challenges.
The symposium featured sessions on everything from the nervous system to orphan diseases to pediatric cancers and drug discovery. For example, during the session “Transformative Approaches to Diseases and Disorders of Childhood,” Philip R. Johnson, MD, chief scientific officer and director of the Research Institute, said that defining the future of pediatric medicine “is a tall challenge.” But Dr. Johnson nonetheless challenged researchers to consider novel ways to advance pediatric care.
Participants also were given the opportunity to meet privately for one-on-one discussions. These meetings allowed investigators to follow up on presentations and discussions, and served as the first step in the development of new collaborations.
“The symposium really exceeded our expectations,” said CHOP Research’s Deputy Scientific Director Tom Curran, PhD, FRS, who led the organization of the symposium. “It set the tone for us to work together, transcending traditional boundaries, and forming unique collaborations with the common theme of improving the health and welfare of children.”
For medical devices, as with many medicines, the market for children is a small fraction of the adult market, and there are far fewer child-sized devices. But the need for pediatric medical devices exists, even if proper devices may not, and a collaborative, multi-institution consortium led by CHOP experts is looking to address this need.
“It’s not simply a matter of scaling down adult equipment for pediatric use,” said Children’s Hospital bioengineer Matthew Maltese, PhD. “Pediatricians have long known that children are not just small adults, and adults are not just big children.”
Dr. Maltese is the principal investigator of the Philadelphia Regional Pediatric Medical Device Consortium (PPDC), which brings engineers and biomedical researchers from CHOP, Drexel University, and the University of Pennsylvania to address the shortage of medical devices designed for children. During fiscal 2013 the PPDC received a $1.5 million, five-year grant from the U.S. Food and Drug Administration (FDA).
This multi-institution consortium will provide clinical, business, and regulatory expertise, as well as seed funding, to help translate innovative ideas into commercial devices for use in young patients. As the center of the nation’s largest pediatric care network, CHOP offers a large, diverse pool of pediatric patients, allowing for carefully regulated clinical trials to test potential medical devices.
Co-principal investigator of the PPDC Robert Levy, MD, sees opportunities to help children, saying that the consortium “will help to address unmet needs for pediatric medical devices.” Dr. Levy’s medical device experience is reflected in his 35 issued U.S. patents that have led to extensive licensing activities, both to established medical device companies and to startups.
In addition, the PPDC will benefit from Dr. Maltese’s own experience adapting medical devices for children in his position in Critical Care Medicine at CHOP. The Hospital is currently collaborating with industry partners to develop pediatric versions of existing FDA-approved cardiopulmonary resuscitation (CPR) quality feedback tools developed for adults. These smartphone-sized devices measure motion and force on a patient’s chest during CPR to rapidly produce sound and visual prompts that improve the quality of CPR and save lives.
“For a variety of reasons, it is difficult to advance pediatric medical devices beyond the idea stage,” Dr. Maltese said. The PPDC provides “innovators with the support they need to transform concepts into practical and available medical devices that benefit children,” he added.
Clinicians and researchers at The Children’s Hospital of Philadelphia and Penn Medicine have developed remarkable expertise in Friedreich’s Ataxia (FA), a rare, progressive neurodegenerative condition that is heavily disabling because it affects a variety of body systems.
A new Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence opened in March to advance this work under the direction of David Lynch, MD, PhD, FA program director at CHOP, and Robert B. Wilson, MD, PhD, professor of pathology and laboratory medicine at the Perelman School of Medicine. The establishment of the Center was catalyzed by a $3.25 million gift from the Friedreich’s Ataxia Research Alliance (FARA), in partnership with the Hamilton and Finneran families.
“We are the center for research on FA for the world,” Dr. Lynch said.
FA is a genetic mitochondrial disease found in approximately one in 50,000 people worldwide. Symptoms usually begin in childhood, and most patients are confined to a wheelchair by their mid-to-late 20s. People diagnosed with FA experience general unsteadiness, motor speech problems, increased heart wall thickness, and a higher tendency to develop diabetes over time. Myocardial failure and/or arrhythmias are the most common cause of premature death. Currently there are no approved drugs to treat FA.
For the past 16 years CHOP, Penn Medicine, and FARA, a nonprofit organization dedicated to curing FA, have collaborated to provide and enhance the care needed by FA patients. The three longtime allies also have shared in research and clinical trials that have elucidated the metabolic dysfunction underlying FA.
One of the Center’s first goals was to establish a biomarker development program with the expertise of Ian Blair, PhD, of the Perelman School of Medicine. This collaboration is the focus of a National Institute of Neurological Disorders and Stroke grant awarded to Dr. Lynch.
“A unique aspect of this grant is our chance to partner on a technique that not only may be useful for understanding the mitochondrial abnormalities that are proposed in FA, but also for monitoring it and related diseases in clinical trials,” Dr. Lynch said.
If successful, this new approach could allow investigators to know within days if a chosen therapy reverses the intracellular mechanisms that go awry in FA and other more common secondary mitochondrial disorders such as Parkinson’s disease and Alzheimer’s.
Another objective for the center was to add cardiac expertise in FA research and clinical care under the leadership of Kimberly Y. Lin, MD, a cardiologist at CHOP with board certification in pediatrics, internal medicine, and pediatric cardiology.
“Integrating cardiac expertise into the care of patients is one major step forward this gift allows us to pursue,” said Philip R. Johnson, MD, chief scientific officer and director of the Research Institute. “Rare diseases are often an area where philanthropy can make a difference, and the generosity of these donors will make a significant impact.”
Investigators at Children’s Hospital work tirelessly to uncover the inner workings of biological systems and the causes of diseases. But making discoveries is only part of the challenge; the next set of challenges often lies in taking the new knowledge from discoveries and working with outside partners to bring promising new therapeutics and treatments to patients.
A new partnership launched in 2013 between Children’s Hospital and the venture-capital fund Osage University Partners (OUP) will expand the opportunities to commercialize the research done at Children’s Hospital, moving the potential for new treatments even closer to patients’ bedsides.
OUP invests exclusively in startup companies that commercialize academic research. It shares part of the resulting profits with those institutions to further promote entrepreneurial opportunities within those centers.
OUP is part of Osage Partners, a family of venture capital funds based in Bala Cynwyd, Pa. OUP has research partnerships with more than 60 universities and research centers, including the University of Pennsylvania, Johns Hopkins University, Carnegie-Mellon University, Drexel University, and Duke University.
The company invests in life sciences, biopharma, and medical devices and diagnostics, in addition to other industries such as those involved in information technology, energy, and materials technology. It typically co-invests in conjunction with other venture companies.
“This partnership offers a mechanism to move our Hospital’s innovative research into the marketplace and better provide health benefits to children and families worldwide,” said Philip R. Johnson, MD, chief scientific officer and director of the Research Institute.
The Children’s Hospital of Philadelphia engages with the community around it in myriad ways, from collaborating with social organizations to organizing fundraisers to working to prevent and reduce violence.
During fiscal 2013 CHOP Research and the Science Leadership Academy (SLA), a Philadelphia public high school focused on the sciences, formed a novel partnership under which SLA students worked in CHOP labs. By being mentored by CHOP investigators, SLA students contributed to a variety of studies while also getting a feel for the daily work and benefits of a career in science.
SLA is a partnership high school with The Franklin Institute that “provides a rigorous, college-preparatory curriculum with a focus on science, technology, mathematics and entrepreneurship.” SLA students have been accepted at prestigious colleges around the country, including the University of Pennsylvania, Princeton University, and Oberlin College, according to the school’s website.
The students worked at CHOP Research through SLA’s Individualized Learning Plan program, which prepares students for adulthood by giving them the chance to work in various organizations around Philadelphia. Students are placed in an array of Philadelphia institutions, from the Academy of Natural Sciences to the Philadelphia Zoo.
CHOP’s SLA partnership is administered by Raymond Colliton, MS, director of CHOP Research’s Office of Research Safety; Wendy Williams, PhD; and Jodi Leckrone, MEd, director and assistant director, respectively, of the Office of Responsible Research Training.
Six SLA students were paired with five Children’s Hospital investigators from a number of disciplines. Pathologist Yair Argon, PhD; geneticist Ian Krantz, MD; cartilage and bone researcher Motomi Enomoto-Iwamoto, DDS, PhD; gastroenterologist Randy Matthews, MD, PhD; and anesthesiologist Francis McGowan, MD; all hosted SLA students. The students, who began working in October 2013, helped in the researchers’ labs for two to five hours one day a week, Leckrone said.
“By exposing these students to research at CHOP, we hope to not only provide them with practical, applicable laboratory skills but also foster an interest in science, research, and medicine,” Dr. Williams said.
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