Developmental Disease Modeling, Gene Discovery and Drug Screening

Technology Overview

Dr. Lisa Maves

Approximately 80% of human disease-linked genes are also found in zebrafish, making the well-characterized fish a promising system to model human pediatric genetic disorders. Developmental biologist Lisa Maves, PhD, is maximizing the potential of CRISPR-Cas9 genome editing technology and zebrafish models to identify the genetic causes of pediatric diseases and conditions such as congenital heart defects and Duchenne muscular dystrophy. Zebrafish models can be used not only for gene discovery and testing genetic variants but also for drug screening. The ultimate goal of this research is to decipher the genetic mechanisms of pediatric disorders and find novel therapies.

The zebrafish platform developed in the Maves Lab is a key technology aiding three main research endeavors:

• Testing genetic variants in pediatric disorders and diseases: Using CRISPR-Cas9 gene editing, the team has demonstrated success in engineering zebrafish to carry a variety of DNA mutations. The Maves Lab was the first to use CRISPR to demonstrate a function for a human gene variant in zebrafish, a PBX gene variant of unknown significance associated with congenital heart defects. Studies in the zebrafish model can provide insight into the roles of selected genes and genetic variants and their potential contributions to normal development, developmental abnormalities and disease processes. The zebrafish platform could be particularly useful for knocking out genes associated with rare diseases to better address the genes’ putative roles in humans.
• Discovering new genetic associations: The team has taken advantage of CRISPR screening in zebrafish to discover new roles for proteasome factors in heart development and congenital heart defects. In a study that modeled congenital heart defects in zebrafish, Dr. Maves and team used CRISPR-Cas9 editing to knock out genes whose functions were not yet known in mice or humans. For several genes that encode proteasome factors, the Maves Lab identified potential roles in heart development and created new mutant zebrafish strains for two of the implicated genes, pomp and psmd6. The researchers’ experiments showed that loss of the proteasome gene function leads to defects in zebrafish heart development and cardiac function that resemble those seen in known congenital heart defect genes (PLOS Genetics, 2025). The team thus has the ability to assess candidate genes for their potential involvement in specific diseases or disorders.
• Screening drug candidates: A recent collaboration is using the zebrafish platform to screen for drugs that alleviate the cardiotoxicity of a commonly used cancer drug. The joint research includes harnessing the power of zebrafish cancer models to screen for new chemotherapeutic agents. These efforts showcase the Maves Lab’s ability to quickly and inexpensively screen large sets of candidate drugs using zebrafish. Additionally, the researchers are using zebrafish as a xenograft model for pediatric medulloblastoma, in which they introduce human medulloblastoma cells into zebrafish embryos and allow the cells to metastasize. Drugs introduced directly into the fish media can be screened for their ability to kill the malignant cells.

Dr. Maves has considerable expertise in using CRISPR screening and precision editing technology in zebrafish, allowing her team to engineer knock-out and knock-in strains and apply these tools to genetic loci involved in a wide variety of defects and diseases. The aquatics facility at Seattle Children’s Research Institute is well-equipped for this work, allowing researchers to maximize the model system’s advantages. Because zebrafish embryogenesis lasts only 3 days, genetic or drug-induced effects can be seen within days, which allows the researchers to quickly assess a gene’s involvement or a drug candidate’s effectiveness.

Dr. Maves is interested in partnerships that will further develop these preclinical models or generate new models and harness her platform’s potential for disease modeling, discovery research and drug testing.

Stage of Development

• Pre-clinical in vivo

Partnering Opportunities

• Collaborative research and development
• Sponsored research agreement
• Consultation agreement
• Animal model access
• High-throughput screening

Learn More

• Lisa Maves, PhD
• Maves Lab
• Identifying and Evaluating Treatments for Duchenne Muscular Dystrophy and Other Muscle Disorders

Publications

1. Farr GH III, Reid W, Hasegawa EH … Maves L. A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects. PLOS Genet. 2025;21(8):e1011579.
2. Karuppasamy M, English KG, Henry CA … Maves L. Standardization of zebrafish drug testing parameters for muscle diseases. Dis Model Mech. 2024;17(1):dmm050339.
3. Hasegawa EH, Farr GH III, Maves L. Comparison of pronase versus manual dechorionation of zebrafish embryos for small molecule treatments. J Dev Biol. 2023;11(2):16.
4. Farr GH III, Imani K, Pouv D, Maves L. Functional testing of a human PBX3 variant in zebrafish reveals a potential modifier role in congenital heart defects. Dis Model Mech. 2018;11(10):dmm035972.
5. Kao RM, Rurik JG, Farr GH III … Maves L. Pbx4 is required for the temporal onset of zebrafish myocardial differentiation. J Dev Biol. 2015;3(4):93-111.

Last updated 6/15/2026