Beach science
Mouse and Fly
Hong and Hamilton 2016

Brain development

Much of our work starts from genetic analyses. Mutations that causes structural brain defects or more subtle abnormalities that alter behavior have led us into several signaling and transcriptional pathways. These include the nuclear receptor Rora, the 30 zinc finger protein Zfp423, and the single zinc finger protein Zfp804a. Each of these genes has been identified to some extent with human illness. Our work primarily focuses on understanding the biology, which may provide a framework for broader approaches to rare disorders.

Brain Disorders

Abnormalities in human development can present a wide range of disorders. Some aspects of developmental disorders can be modeled effectively in experimental systems. Humans with mutations in ZNF423 (JBTS19) have structural abnormalities homologous to Zfp423 mice. We use mice and cell models to understand mechanisms affected by patient mutations and their relative severity. We have also detected additional genetic loci that modify the survival or anatomical consequences of Zfp423 mutations.

Modifier genes

Anything interesting in biology is likely to be complex. Even disorders caused by a single gene often appear differently in different people–or flies, or fish, or mice. We use a variety of approaches to identify modifier genes–variations that change the outcome of a "disease" mutation. This has led in some unexpected directions, inlcudiong the discovery that a single amino acid substitution in the mRNA nuclear export factor Nxf1 modifies a whole class of mutations cause by retrovirus insertions in introns of other genes.


The most exciting thing in science is not "Eureka," but rather, "that's funny." 1  Some projects arise from things we just don't understand and are better positioned to pursue than other labs.  We found a novel gene (Nmf9) with an unusual evolutionary history and strong conservation of non-motif sequences. Parallel mutations in mice, fish, and flies show its requirement in balance, locomotion, and other neurological functions.

1 Attributed to Isaac Asimov.

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