Our lab uses molecular genetic tools to study the reproduction and development of a variety of organisms, from mice to sharks. Currently, work in the lab is focused on four unique areas of study - the epigenetic control of mammalian development, mammalian brain development and neurodevelopmental disorders, mammalian limb development, and the population genetics of sharks.

Regulation of genomic Imprinting. Mammalian organisms inherit one copy of each gene from their mother and one copy from their father, and most genes are expressed equivalently from each copy. A group of ~100 genes defies this rule, however, being expressed from only one of the two parental alleles. These are the imprinted genes, and the process that regulates their parental-specific expression is called genomic imprinting. Imprinted genes play important roles in mammalian growth and development, and their deregulation underlies many human congenital diseases and is involved in the etiology of cancer. The mouse, Mus musculus, is being used as a model system to investigate the developmental functions of imprinted genes, and to identify the mechanisms that regulate genomic imprinting.

A mouse model for congenital hydrocephalus. Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, is the most common human neurodevelopmental disorder. This disease occurs in 1 in every 500 children, and if left untreated causes increasing neurological damage that leads to cognitive and motor defects. Our lab has developed a mouse model for juvenile hydrocephalus (Jh mice). These mice develop hydrocephalus by 2 weeks of age, and results from the mutation of a single novel gene whose function is unknown. We are using a combination of molecular, biochemical and microscopic techniques to characterize the neural defects of Jh mice, and to understand the normal function of the Jh gene.

A novel gene expressed in the developing mammalian limb. The developing mouse limb forms initially as the limb bud, a flattened “paddle” of tissue. Subsequently, cartilage rays appear that delineate the developing digits, and the interdigital mesenchyme (IDM) tissue joining the digits undergoes apoptosis. Our lab is studying a gene trap integration that is expressed in the presumptive IDM early in limb development. There is evidence that the IDM specifies digit identity, and the early expression of this gene suggests that it may be involved in digit specification. We are using a combination of gene expression analysis and transgenic mice to identify the trapped gene and determine its function.

Population and reproductive genetics in the whale shark (Rhincodon typus). The whale shark is the largest shark and the largest fish, reaching lengths of 45 feet or more. They are planktivorous filter-feeders who get their name from their large size and method of feeding. Whale sharks are open ocean animals, but gather in large feeding aggregations in certain parts of the world at predictable times. A key question for both the biology and conservation of whale sharks is whether these aggregations represent isolated breeding populations of animals, or whether whale sharks are migratory and composed of a single global population. As active fisheries exist for whale sharks in many countries, their migratory patterns can determine the risks they face. We are using genetic analysis to understand the genetic relatedness of whale sharks found in different parts of the world.