To Harness a WHIRLWIND

Center for Pediatric Genomics Applies Structure to a Surging Flow of Discovery

by Tim Bonfield

On paper, it can look orderly, structured, and almost simple. But the cycle of discovery fueled by the revolution in genomic science is more like a cyclone, surging forward, spinning faster, and changing everything in its path.

The enormous potential of genomics to transform medicine makes these exciting times to be working in biomedical science. The breakneck pace of new developments, however, makes it all the more urgent to fully understand the implications of this evolving field and be prepared for the changes to come. This is the goal behind the new Center for Pediatric Genomics at Cincinnati Children’s - to usher in a sea change in the relationship between research and clinical practice.

John Harley, MD, PhD, (left) and Peter White, PhD, co-direct the Center for Pediatric Genomics at Cincinnati Children’s.

John Harley, MD, PhD, (left) and Peter White, PhD, co-direct the Center for Pediatric Genomics at Cincinnati Children’s. Meet our steering committee and support team.

“Our capacity to explore ideas about how things work has changed so much that we’re doing experiments today that were impossible two years ago,” says John Harley, MD, PhD, who co-directs the center with Peter White, PhD. “The databases we have at our disposal are vastly larger and growing exponentially, which offers tremendous opportunity. But bringing utility to all this takes a new level of concerted, dedicated effort.”

Says White: “Five years from now, genomics will be considered much more a standard part of clinical practice. Yet there’s tremendous uncertainty about the changes genomics will bring, not just for patients and families, but also for clinicians. The uniqueness of the center is that it seeks to establish genomics as a community of practice across an entire institution.”

Cincinnati Children’s launched the Center for Pediatric Genomics in 2014, but the center actually reflects more than 15 years of investment to acquire the latest gene sequencing and gene editing technologies, to expand computing power, to develop ethical methods for mining electronic medical records, and most importantly, to recruit a world-class team of experts to put it all together to improve outcomes for children.

So, what is the Center for Pediatric Genomics? On one level, the center functions as an incubator for innovation that has already provided support to more than 20 new and promising projects. On another level, the center serves as a catalyst for integrating genomics into everyday medicine.

Learn more about our Center for Pediatric Genomics

UNDISCOVERED FRONTIERS

The projects supported by the center reflect the wide range of ways genomics will influence the future of pediatric medicine. Some projects seek cures for rare, almost untreatable conditions. Others search for solutions to stubborn complications that occur in cancer treatment and organ transplantation. Some seek to scale up the entire field to take on common but far more genetically complex conditions such as epilepsy, diabetes and asthma.

Still other projects explore more foundational questions, such as studying the formation of chromatin loops and the role they play in regulating gene expression, or searching for better methods to distinguish a risk-causing gene mutation from a “variant of unknown significance.”

Harley says no one can predict where the work may lead.

“If you could stretch out a full strand of DNA, it would be about three meters long. But the strands of the DNA in our chromosomes are actually boxed up into a ball so tiny that we cannot see it. Indeed, there are about 10 trillion of these in the adult human body,” Harley says. “We used to think there was no particular significance to the way that folding occurs, but now we know that it matters very much. That’s just one aspect of genomics that remains minimally understood. It may take the rest of the century to figure out what exactly causes the many differences in our genome, and why.”

NEW KINDS OF CARE TEAMS

Some of the center’s work explores how all this new science will play out as more clinicians become involved in using and communicating genomic information and more families face decisions based on that information.

The emergence of genomics and the promise of personalized, precision medicine is driving new relationships between clinicians and research scientists. In addition to working directly with patients, this may mean that physicians must also interact effectively with a behind-the-scenes army of experts, including computational biologists, cytogeneticists, biostatisticians, programmers, advanced laboratory technicians, bioethicists and others.

Working out the best ways to work together will be a massive undertaking, which is why the center expects to play a major role in training and raising awareness in the clinical world about resources available on the research side.

FORGING MASSIVE NETWORKS

Harley and White emphasize that translating the potential of genomic innovation into improved medical practice will depend heavily on research centers working together at institutional levels. Cincinnati Children’s already leads several big research collaborations and participates in many others.

An important role for the center will be to support even more multi-center projects.

“Our challenge is that the complexity of genomics precludes the old models for conducting research and providing care,” White says. “Very few, if any, advances in this field will come from researchers in isolated labs, or even from single institutions. This truly is the era of team science.”

 


Funding Innovation

The Center for Pediatric Genomics (CpG) at Cincinnati Children’s fosters and incubates outstanding and innovative scientific and translational genomics projects. These projects have received funding for pilot studies:

Vidya Chidambaran, MD
Anesthesia
Genetic-Epigenetic Approach to Predict Chronic Post-Surgical Pain in Children

Andrew Dauber, MD
Cincinnati Center for Growth Disorders
Confronting the Dreaded VUS: Validation of Exome Sequencing Candidates in Human Growth Disorders Using Genome Editing

David Haslam, MD
Infectious Diseases
Fecal Metagenomics as a Tool to Identify and Mitigate Risk of Bloodstream Infection in High Risk Children

Hong Ji, PhD
Asthma Research
Epigenetic Mediation of Genetic Effects in Childhood Asthma

Andrew Lindsley, MD, PhD
Artem Barski, PhD
Pediatrics
Epigenetic Mechanisms of Humoral Immune Deficiency in Kabuki Syndrome

Q. Richard Lu, PhD
Brain Tumor Center
Functional Genomic Analysis of Oncogenic Pathways in Primary and Recurrent Medullablastomas

Melanie Myers, PhD
Genetic Counseling Graduate Program
A Decision Aid for Return of Results across Genomic Sequencing Studies

Mihaela Pavlicev, PhD
Pediatrics
The Contribution of Non-Coding Genome to Placental Defects: The Establishment and Application of a Novel Tool to Reliably Map and Quantify Active Enhancers

Matthew Weirauch, PhD
Center for Autoimmune Genomics and Etiology
Etiology of Inflammatory Diseases Revealed by Shared Molecular Mechanisms

Susanne Wells, PhD
Epithelial Carcinogenesis and Stem Cell Program
HPV Infection of Human Epidermis: Single Cell Resolution & Metabolomic Consequences

Hansel Greiner, MD
Neurology
Biomarker Development in Focal Cortical Dysplasia

Taosheng Huang, MD, PhD
Human Genetics
Mutations in SLC25A46 Cause AutosomalRecessive Optic Atrophy and Axonal Peripheral Neuropathy

Sonata Jodele, MD
Bone Marrow Transplant and Immune Deficiency
Genetic Predisposition for Thrombotic Microangiopathy

Kenneth Kaufman, PhD
Center for Autoimmune Genomics and Etiology
Validation of Arg>Cys 77 AGER Polymorphism in Hereditary Pulmonary Alveolar Proteinosis

Kasiani Myers, MD
Bone Marrow Transplant and Immune Deficiency
Inherited Bone Marrow Failure: Mechanisms and Therapy Through Gene Discovery

Derek Neilson, MD
Human Genetics
Genomic Approach to Prevent a Painful Syndrome: Ehlers Danlos Hypermobility Type

Steve Potter, PhD
Developmental Biology
Genetics of Hepatoblastoma and Congenital Kidney Disease

Senthilkumar Sadhasivam, MD, MPH
Pain Management
EMR Machine Learning and Validation of Genetic Associations and Postoperative Pain and Opioid
Outcomes in Children Undergoing Tonsillectomy

Rolf Stottman, PhD
Human Genetics
Forward Genetic Analysis of Congenital Craniofacial Malformations

James Wells, PhD
Developmental Biology
Generating Corrected Beta Cells from Patients with Genetic Forms of Diabetes

Chunyue Yin, PhD; Alexander Miethke, MD
Gastroenterology, Hepatology & Nutrition
Identification and Functional Relevance of Gene Variants in Progressive Familial Intrahepatic Cholestasis Patients

Learn more about our Division of Biomedical Informatics