The National Disease Research Interchange (NDRI), in collaboration with the University of Maryland School of Medicine and Johns Hopkins All Children’s Hospital, has been awarded a research grant of $14.4M by the National Institutes of Health (NIH) with a goal to transform our knowledge of how much genetic variation there is in cells and tissues throughout our bodies.
The five-year award is part of a new NIH Common Fund program called the Somatic Mosaicism across Human Tissues (SMaHT) Network. The initiative will provide the first comprehensive public resource for analyzing genetic variation due to somatic mosaicism in human tissues from all developmental layers in the human body.
“NDRI is thrilled to serve as the Tissue Procurement Center for the SMaHT Network,” says Bill Leinweber, President and CEO of NDRI. “Human tissue is the fundamental resource for achieving the objectives of the SMaHT Network. I am confident our tissue procurement expertise, as demonstrated with other landmark federal research initiatives, will serve to enable research and discovery mediated by genomic variation in somatic tissues.”
Somatic mosaicism is a phenomenon caused by spontaneous mutations in the DNA sequence in cells after fertilization. These genetic alterations create a “mosaic” of cells with distinct genotypes during development and aging. Although somatic mutations are widespread and common during normal development, their implications on disease and human health are still largely unknown.
“The SMaHT Network is poised to make significant contributions to our understanding of how genetic variation contributes to overall health and disease,” says Dr. Melissa VonDran, Senior Vice President of Operations and Biorepository Director at NDRI. “NDRI is excited to be part of such an innovative initiative and we look forward to working with our partners to create a resource for the scientific community that will advance a range of critical research aims.”
NDRI, along with collaborators at the University of Maryland and Johns Hopkins All Children’s Hospital, will serve as the Tissue Procurement Center (TPC) for the SMaHT Network. NDRI will work with a network of organ procurement organizations to collect, store, and distribute multiple healthy tissues across body systems from a diverse pool of at least 150 organ and tissue donors. Brain tissue processing and biobanking along with pathology analysis of all tissue samples will be led by experts at the University of Maryland School of Medicine.
“We are thrilled to be working with NDRI and Johns Hopkins All Children’s Hospital as the Tissue Procurement Center in support of the SMaHT Network,” says Dr. Thomas G. Blanchard, Associate Professor of Pediatrics at the University of Maryland School of Medicine and Director of the University of Maryland Brain and Tissue Bank. “The breadth, innovation, and talent of the SMaHT Network investigators favors truly remarkable advancement in our understanding of the influence of genetic mosaicisms on cellular regulation, programming, differentiation, and function. The success of this initiative is dependent on the acquisition, characterization, and distribution of high-quality tissues and we are excited to be a partner in providing such an important resource in support of the SMaHT scientific objectives.”
The SMaHT Network also includes an Ethical, Legal, Social Implications (ELSI) study to further our understanding of human tissue donation for genetic research. The SMaHT ELSI study will evaluate tissue requesters and family decision makers with a focus on diversity, equity, and inclusion to gain broad perspectives on ELSI factors for tissue donation.
Dr. Raquel Hernandez, Associate Professor of Pediatrics and Director of the Center for Pediatric Health Equity Research at Johns Hopkins All Children’s Hospital, adds that their ELSI team is excited to implement its Diversity, Equity, and Inclusion 360° model in this project. This will be used to conduct focus groups and interviews with donor families, tissue requesters, and community members to explore attitudes, knowledge, and beliefs related to tissue donation studies focused on somatic tissue variation. The goal of this work is aimed at finding greater support for families and teams in end-of-life conversations related to tissue donation and genomic research.
The SMaHT Network joins other large-scale initiatives supported by the NIH aiming to map human development. The data from the SMaHT project will create an unparalleled research resource for the advancement of our understanding of somatic mosaicism.
This work is supported by the National Institutes of Health grant #1 U24 MH133204-01.