Understanding Organ Development

Using genomics, genetics, and mouse models to identify disease mechanisms and novel therapeutic targets

Technology Overview

Dr. David BeierDr. David Beier seeks the root causes of human disease and developmental abnormalities using leading-edge genetic methods and customized model organisms. The Beier group primarily studies organ development using mouse models. They have experience in the phenotype-driven approach of embryonic screening for developmental defects and cloning and characterizing the causal genes.

Using this approach, Dr. Beier and colleagues identified a mouse model of a rare kidney disease in children. Characterization of the model determined that it has fundamental similarities to human polycystic kidney disease, which affects 600,000 people in the United States. Dr. Beier's group is using this and other mouse models to identify interacting genes and pathways that cause and modify the development of polycystic kidney disease. Their work shows that their mouse models are suitable for studying renal cystic disease in humans, including identifying therapeutic targets and evaluating novel therapies.

Dr. Beier is also an expert in genotype-driven strategies such as genomewide analyses for previously uncharacterized genes that are likely to be essential for a developmental process. His group has the capabilities and resources to use methods such as CRISPR technology to alter candidate genes in mice. They are experienced in conducting biochemical and genetic analyses to determine the mechanisms by which the genes contribute to congenital disorders and disease.

Dr. Beier is interested in partnerships that make use of his knowledge and skills in bioinformatics and in vitro and in vivo genetic methods. His expertise includes animal model and cell line development, genomics including quantitative trait loci (QTL) analysis, and identifying and characterizing genes that influence human disease and development.

Stage of Development

• Pre-clinical in vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement
• Tissue sample access

Publications

1. Weghorn D, Balick DJ, Cassa C, Kosmicki JA, Daly MJ, Beier DR, Sunyaev SR. Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans. Mol Biol Evol. 2019;36(8):1701-1710.
2. Bittermann E, Abdelhamed Z, Liegel RP, Menke C, Timms A, Beier DR, Stottmann RW. Differential requirements of tubulin genes in mammalian forebrain development. PLoS Genet. 2019;15(8):e1008243.
3. Ha S, Tripathi PP, Daza RA, Hevner RF, Beier DR. Reelin mediates hippocampal Cajal-Retzius cell positioning and infrapyramidal blade morphogenesis. J Dev Biol. 2020;8(3):E20.
4. Geister KA, Timms AE, Beier DR. Optimizing genomic methods for mapping and identification of candidate variants in ENU mutagenesis Screens Using Inbred Mice. G3 (Bethesda). 2018 Feb 2;8(2):401-409.
5. Cassa CA, Weghorn D, Balick DJ, … Beier DR, et al. Estimating the selective effects of heterozygous protein-truncating variants from human exome data. Nat Genet. 2017; 49: 806-810.
6. Beier DR. High-resolution genetic localization of a modifying locus affecting disease severity in the juvenile cystic kidneys (jck) mouse model of polycystic kidney disease. Mamm Genome. 2017; 27: 191-199.
7. Tran PV, Talbott GC, Turbe-Doan A, …Beier DR. Downregulating Hedgehog signaling reduces renal cystogenic potential of mouse models. J Am Soc Nephr. 2014; 25: 2201-2212.
8. Gallego-Llamas J, Timms AE, Geister KA, Lindsay A, Beier DR. Variant mapping and mutation discovery in inbred mice using next-generation sequencing. BMC genomics. 2015; 16: 913. 

Learn More

• David Beier, MD, PhD