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Hyejung Won Karen Mohlke Mike Love

Hyejung Won (PhD, Assistant Professor, Department of Genetics, Neuroscience Center), Karen Mohlke (PhD, Professor, Department of Genetics), and Mike Love (PhD, Assistant Professor, Department of Biostatistics, Department of Genetics), were awarded a 5-year $9.25 million UM1 grant from the National Human Genome Research Institute (NHGRI) titled “Systematic in vivo characterization of disease-associated regulatory variants”.

The UM1 awarded to Drs Won, Mohlke, and Love is one of 25 awards across 30 US research sites that will form the new Impact of Genomic Variation on Function (IGVF) Consortium initiated and funded by the NHGRI at NIH. NHGRI has committed ~$185 million over the next 5 years to the IGVF consortium with the goal to “understand how genomic variation alters human genome function and how such variation influences human health and disease”. The IGVF consortium includes five components: Functional Characterization Centers (including this UM1), Regulatory Network Projects, Mapping Centers, Predictive Modeling Projects, and a Data and Administrative Coordinating Center. The NIH news release for the IGVF consortium can be found here and the consortium website, which includes a full list of research awards and sites, can be found here.

The goal of the UM1 Functional Characterization Center at UNC is to systematically characterize the impact of human genetic variation on gene regulation via massively parallel reporter assays (MPRA). The gene regulatory effect of ~500,000 variant alleles selected from genome-wide association studies (GWAS) for common diseases and complex traits will be interrogated in five organs (brain, liver, lung, muscle and heart) under physiological conditions at baseline and in a perturbed inflammatory state using systemic circulation of adeno-associated viral (AAV) MPRA libraries in a mouse model. Data generated from the UNC Characterization Center will provide ~10 million allelic effect data points that encompass tissue-, sex-, and perturbation-specific regulatory effects and will contribute to the IGVF Consortium regulatory variant catalog for the community.

The UNC Functional Characterization Center led by Drs Won, Mohlke, and Love will be a collaborative effort with UNC Co-Investigators Yun Li (PhD, Professor, Department of Genetics), Bev Koller (PhD, Associate Professor, Department of Genetics), Jude Samulski (PhD, Professor, Department of Pharmacology, Gene Therapy Center), Adriana Beltran (PhD, Associate Professor, Department of Genetics) and Program Manager Sarah Schoenrock (PhD, Assistant Professor, Department of Genetics). The UNC Functional Characterization Center will also rely heavily on the exceptional core facilities in the School of Medicine at UNC including the Animal Studies Core (led by Charlene Santos), Flow Cytometry Core, Vector Core, High-Throughput Genomic Sequencing Facility, and the Human Pluripotent Cell Core (led by Dr. Adriana Beltran).

The SOM news story can be found here.