Cultivating a World-class Academic Medical Research Community

Children's Hospital of Philadelphia Research Institute and Arcus, CHOP's centralized research data repository, launched its first genomic dataset that includes more than 5,000 exomes and genomes and 12,000 chromosomal SNP arrays this year. The availability of this data will allow CHOP investigators to perform large-scale research while protecting patients' privacy.

Easy, hassle-free access to data is important for researchers to complete their work. This is particularly relevant in the genomics sphere where there is strength in numbers; however, genomic data is so sensitive that sharing it is not straightforward. To overcome this challenge, Arcus built a system within CHOP to make its institutional data available for researchers while providing a state-of-the-art privacy framework.

"A unique aspect of Arcus is that it can act as the honest broker on behalf of our researchers to collect and provide access to de-identified data, particularly the continuous update of rich clinical data that can be linked to genomic data," said Ingo Helbig, MD, scientific director of the Arcus Omics Team.

The skyline alongside Philadelphia's Schuylkill River will look a little different come 2025, as developers broke ground on the Schuylkill Avenue Research Building. Standing at 14 stories with 350,000-square feet of space, this state-of-the-art research facility will continue Children's Hospital of Philadelphia's century-long commitment to advancing children's health through innovative research.

"This building is an important part of our strategy to advance research at CHOP," said Doug Hock, CHOP Executive Vice President and Chief Operating Officer, at the groundbreaking ceremony. "It will make it easier for our teams to collaborate on the bench-to-bedside strategy CHOP is known for. It will help us attract and retain the very best scientists. It will make it possible to translate their discoveries into new treatments to change children's lives."

The international architecture firm Cannon Design created the Schuylkill Avenue Research Building’s overall layout to encourage all the components of successful scientific discovery: collaboration, flexibility, and a dynamic nature. Wet labs, where scientists conduct biochemical and molecular studies, will be situated next to dry labs, where researchers analyze data sets, create computational tools, and develop new hypotheses for wet lab studies. The developers anticipate such a layout will stimulate a more seamless exchange of ideas and communication between researchers.

Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania jointly launched the Penn-CHOP Kidney Innovation Center, in an effort to improve the lives of children and adults with kidney disease. During its first year, the Center hosted its inaugural symposium, recruited two new faculty members, hosted an international meeting, and launched its monthly seminar series.

The Kidney Innovation Center brings together scientists from across disciplines to focus on three main areas: fostering cutting-edge discoveries through collaboration between CHOP and Penn; recruiting and growing top talent to key areas that align with the Center's mission; and building the next generation of nephrology researchers through an enhanced training and mentorship program.

"We started with the symposium with the goal of bringing together people from many different fields, and that was quite successful," said Michelle Denburg, MD, MSCE, director of research for the Division of Nephrology at CHOP and an associate professor of Pediatrics and Epidemiology at Penn. She leads the Kidney Innovation Center with Penn's Katalin Susztak, MD, PhD, a professor of Nephrology and Genetics. "The Center's ultimate vision is to provide an organizational framework that harnesses the unique strengths of CHOP and Penn to create an integrated clinical care and research model that will benefit patients with kidney disease across their life course."

Following the success of the symposium, the Center's momentum continued with the Penn-CHOP Kidney Innovation Center's Seminar Series, which features monthly research in progress by postdocs, fellows, and faculty within the Penn-CHOP community. In May 2023, CHOP and Penn also hosted the biennial International Podocyte Meeting, bringing more than 400 scientists and clinicians from around the world together in Philadelphia. The formation of the Center also allowed CHOP and Penn to create a combined pediatric-adult fellowship in nephrology.

Children's Hospital of Philadelphia selected its inaugural pair of scientists to participate in the Research Institute's Bridge to Faculty Program.

Its goal is to prepare trainees from historically underrepresented groups for tenure-track faculty positions. Similar to the mentored phase of the National Institutes of Health's Pathway to Independence Award, the Bridge to Faculty Program provides a competitive salary, research training, and professional development that will put postdoctoral fellows on the competitive and rigorous path to professorship.

"This is a unique training experience designed to prepare exceptional senior-level trainees to be competitive in the tenure-track job market," said Paulette McRae, PhD, associate director of Specialty Programs and Diversity in the Office of Academic Training and Outreach Programs at CHOP's Research Institute. "The program not only focuses on scholars getting positions, but simultaneously provides them with the tools needed for success as they launch their independent academic careers."

Bridge to Faculty Program participant Amaliris (Ama) Guerra, PhD, is investigating how to fine-tune the immune system to deliver iron in a way that will safely increase red blood cell production in patients with thalassemia, who are at risk of iron overload. Another participant Zila Martinez-Lozada, PhD, researches the communication of cells in the brain using a combination of cell culture microscopy and transcriptomics, a technique used to study a cell's RNA molecules.

"I'm the product of all of these Philadelphia programs intended to create opportunity for people like me and to diversify academia. That has weight," Dr. Guerra said. "Now I get the opportunity to do science as a real job, which is something that doesn't exist for a lot of people."

Inborn errors of metabolism (IEM) are rare genetic disorders resulting in deficiency of key metabolic enzymes and can lead to serious complications if not treated or managed properly. Patients with inborn errors require close medical follow-ups, and most diagnoses are also associated with repeated hospitalizations.

The Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program is a new Children's Hospital of Philadelphia Frontier Program announced this year to improve outcomes for these patients by creating a nationally renowned center dedicated to translating new molecular therapies from bench-to-bedside.

For the first time, curative molecular therapies are on the horizon for IEMs; however, for any treatment to be successful, it must be given early in the disease course, and patients must receive high quality subspecialist care for their many comorbidities.

Over the next three years, the GTIMD Frontier Program team — led by Rebecca Ahrens-Nicklas, MD, PhD; Can Ficicioglu, MD, PhD; and Sanmati Cuddapah, MD, all members of the Division of Human Genetics — aims to develop an innovative clinical program dedicated to the longitudinal care of IEM patients treated with molecular therapies. Additionally, they aim to translate novel molecular therapies developed at CHOP and the University of Pennsylvania into first-in-human clinical trials for IEM.

"We are so excited to move the transformative new therapies being developed at CHOP and Penn into the clinic in order to improve the quality of life for our patients," Dr. Ahrens-Nicklas said.