New Translational Neuroscience Center is BRIDGE between Genetics and Therapies

BRIDGE is a creative space for CHOP researchers who study childhood brain disorders to connect and collaborate.

The Center for Brain Research in Development, Genetics, and Engineering (BRIDGE), a new Center of Emphasis at Children's Hospital of Philadelphia Research Institute, is a creative space for CHOP researchers who study childhood brain disorders to connect and collaborate. BRIDGE aims to better understand the basic and translational mechanisms of neurodevelopmental disorders and develop novel therapies by linking ongoing efforts on campus in genetics, genomics, cell and gene therapy, and neuroengineering.

"It's a new space centered around science and shared interests rather than divisional or department affiliation," said BRIDGE Director Ethan Goldberg, MD, PhD, a core faculty member in the Center. "We aim to move toward the common goal of modeling and ultimately developing new therapies for brain disorders in childhood."

An Opportunity for Collaboration

The term "neurodevelopmental disorders" is broad and includes genetic and acquired influences on normal brain development that cause it to go awry. Pediatric neurodegeneration, mitochondrial disease, and perinatal brain injury are also among the disorders the Center laboratories focus on.

"There may be some convergent and divergent mechanisms of these disorders," said Dr. Goldberg, who is also an Associate Professor of Neurology, Neuroscience, and Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. "And understanding the ways in which they're similar or different may give us insight into disease pathogenesis."

By studying genetics, researchers gain insight into disease mechanism and some specificity where they can develop an experimental model system, such as a stem cell-derived neuron, or work with murine and fruit fly models.

The engineering piece of the BRIDGE Center is reflected in the approaches the team takes when studying model systems and implementing new therapies, while leveraging the platform technologies space planned for the first floor of the new Morgan Center for Research and Innovation, scheduled for completion in 2025.

Naiara Akizu, PhD

"The BRIDGE Center is an opportunity for collaboration between researchers who are working toward the same objective but using different tools, models, and approaches," said Naiara Akizu, PhD, whose lab is in the BRIDGE Center. "By leveraging these collaborations, we build on everyone's specific knowledge."

Vibrant Community to Move Field Forward

The BRIDGE Center is anticipated to occupy three floors in the Morgan Center for Research and Innovation. Faculty members of the BRIDGE Center will include CHOP faculty, as well as new recruits "to fill in gaps either in terms of content area or approach," Dr. Goldberg said. All the labs have thriving research groups with graduate students, postdoctoral fellows, and clinical research-oriented residents and fellows, as well as extramural research funding.

The laboratories within the Center are led by core faculty members:

• Goldberg Lab investigates mechanisms of cerebral cortical circuit function and circuit dysfunction in neurodevelopmental disorders.
• Akizu Lab studies human brain complexity in health and disease to uncover therapeutic targets for pediatric neurodegenerative disorders.
• Eisch Lab seeks to investigate limbic circuitry, mental function, and new neurons of the postnatal brain.
• Song Lab aims to elucidate the cellular and molecular basis governing neural circuits under physiological and pathological conditions.
• Ortiz-Gonzalez Lab investigates whether mitochondrial dysfunction is a common, underlying factor in rare pediatric neurodegenerative disorders.
• Cristancho Lab studies the epigenetic mechanisms driving long-term neurodevelopmental disabilities from prenatal and perinatal brain injury.

Ethan Goldberg, MD, PhD

"It will be a vibrant community for young people to interact and bring new perspectives and ideas to some intractable problems in neuroscience and disorders of the developing brain — and hopefully move the field forward," Dr. Goldberg said.

Positioned Between Two Research Initiatives

As the name suggests, the BRIDGE Center is positioned between two major research initiatives at CHOP: the Omics Initiative and the Cell and Gene Therapy Collaborative.

On one side, the Omics Initiative is focused on using genetics, genomics, and other omics to better understand and improve children's health. Working with vast amounts of data, they are striving to identify genetic contributions to disease and potential targets for therapy.

On the other side, the Cell and Gene Therapy Collaborative helps investigators to accelerate clinical trials, training, and research to bring life-saving therapies from bench to bedside.

The Center will be working in synergy with these entities by bridging the genetics and the treatments focused on neurodevelopmental disorders toward novel therapeutics. For example, BRIDGE researchers can generate novel models and test candidate targets and potential therapies. This can provide an understanding of both the basic biology that decides how these genes target function and how those processes are altered in childhood brain disease.

"An understanding at the deep mechanistic level is critical toward actually delivering on the promise of our advances in genetic testing and genetic diagnosis and now our emerging abilities to deliver genes to the brain using gene therapy," Dr. Goldberg said.