Discovery of effective prevention and treatment efforts for childhood disease hinges upon the ability for scientists to study and understand the genetic code of pediatric organs and tissue throughout all developmental periods.

Studying how gene expression — the process of converting DNA instructions into a functional product such as a protein — is regulated in adult organs already has identified specific genes associated with five diseases: bipolar disorder, coronary artery disease, Crohn's disease, rheumatoid arthritis and type 1 diabetes. These discoveries have launched new directions in research efforts that continue to promote more effective treatment and management of these complex conditions.

Johns Hopkins All Children’s Hospital is part of a $12.5 million grant to seek similar insight into gene expression in the organs of children who are at various stages of development. The developmental Genome Tissue Expression Project (dGTEx) will be a national, multisite study involving a multidisciplinary team of experts led by the National Disease Research Interchange in Philadelphia.

A unique focus of the dGTEx study will include understanding the challenges of engaging family decision makers in this type of research study because the study involves tissue collection after children die. Johns Hopkins All Children’s received a $1.6 million grant over five years to study the ethical, legal, and social implications (ELSI) of approaching families about organ and tissue donation when they have lost a child or their child is managing end of life care. The team also will focus on how to successfully recruit a diverse pool of donors to help make sure genetic information discovered in the study will equitably benefit all children.

The Center for Pediatric Health Equity Research in the Johns Hopkins All Childrewiln’s Institute for Clinical and Translational Research, l lead the study titled, “Targeting Diversity, Equity and Inclusion Efforts (DEI) in Defining the ELSI for dGTEx Tissue Collection among Tissue Requesters (TRs) and Family Decision Makers (FDMs) of Deceased and At-Risk Children.” The study will focus on evaluating perspectives from research staff who approach families for tissue donation as well as assessing perspectives from family decision makers. Participants will be recruited from a geographically and racially/ethnically diverse population from five pediatric specialty hospitals. Further, at least seven organ procurement organizations will be part of the study.

“This study provides an incredible opportunity to include perspectives from culturally and linguistically diverse families, tissue requesters, as well as community partners on a highly sensitive and challenging topic,” says Raquel Hernandez, M.D., M.P.H., FAAP, assistant professor of pediatrics, principal investigator of the research study, and director of the Center for Pediatric Health Equity Research at John Hopkins All Children’s. “Including a 360-degree approach is novel and will give us critical perspectives on best practices related to pediatric tissue donation.” 

When researchers conducted the Genome Tissue Expression (GTEx) Project with adults, they determined donor families had limited understanding of how the tissues would be used and a false expectation of receiving test results. The adult donor pool was predominantly Caucasian males, leaving gaps in learning about gene expression in a more diverse population. The new project hopes to avoid those pitfalls with the Johns Hopkins All Children’s study.

“There were some critical lessons learned in the GTEx study as to how to better connect the perspectives and experiences of families surrounding the ethical and social challenges of tissue donation into the broader tissue collection efforts,” Hernandez says. “The greater connection our study team can promote between our findings and tissue collection efforts, the more successful the larger study will be discovering mechanisms of pediatric disease onset. This is an opportunity our center and team are thrilled to take on.”

The Johns Hopkins All Children’s team will interview family decision makers who consent to donate their child’s tissue, conduct multilingual surveys and focus groups with family members, and survey tissue requesters. They also will work with community organizations that can enhance the diversity and inclusion approach.

Melissa Faith, Ph.D., ABPP, is a board certified, licensed psychologist at Johns Hopkins All Children’s Hospital, assistant professor in the Johns Hopkins University School of Medicine, and co-investigator with Hernandez on the grant.

“It is an honor and a privilege to walk with families through a child’s end of life care,” Faith says. “Families in this situation are often experiencing one of the most vulnerable times of their lives. Our ultimate goal is to learn the most respectful, mindful ways to provide these families with opportunities to participate in genetics research. We are also strongly invested in learning how to help the dGTEx study procure the most diverse sample possible to enhance health outcomes for all children.”

Faith has helped coordinate a team of clinical psychologists from around the country to help conduct focus groups with families and to serve as a think-tank in these issues. She will also work alongside Hernandez to combine their joint expertise in caring for families through a child’s end of life care.

The overall grant — a collaboration among Johns Hopkins All Children’s, the National Disease Research Interchange (NDRI), Children’s Hospital of Philadelphia and the University of Maryland — is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS).