The Fisher Lab

Research Interests

Craniofacial defects, affecting formation of the face and skull, affect 1/1000 children and are one of the most common categories of birth defects. Although sometimes these disorders are caused by single gene mutations, in most cases the risks are more complex, likely due to multiple genes and environmental factors, and the mechanisms poorly understood.

My lab uses the zebrafish as a model organism to study disorders of the skeletal system, with a particular focus on craniofacial development. We have developed genetic tools and imaging methods to study the skull, and are applying these to better understand the mechanisms of human craniofacial development and the genetic risks underlying craniofacial birth defects.

Current Research

Tools and methods to image skull development

We have developed methods to carry out serial confocal imaging of individual fish, to capture the dynamic events of skull formation. Using this approach, we have created publicly available datasets of bone, cartilage, and osteoclast distribution during skull development.

Chondrocytes Osteoblasts
Confocal imaging of skull formation in a single zebrafish, from 18 to 32 days of development (Michelle Kanther).
Osteoclast distribution in developing skull
Composite of osteoclast distribution in the developing skull (Kelly Miao).

Genetic risk for craniofacial disorders

My group pioneered the use of zebrafish to analyze transcriptional and regulatory elements from the human genome, and have identified and studied dozens of enhancers associated with skeletal genes.

Using these and other powerful tools for genome editing, we are exploring the genetic risk for craniofacial disorders in humans, identified through genome–wide association studies or sequencing of patient cohorts. In particular, we are working to understand the mechanism of genetic risk associated with several genes in the BMP signaling pathway.

Transgenic screen
Transgenic screen for human enhancers from the human genome associated with genetic risk for craniofacial birth defects (Anita He).