Research Interests

Genomics

We develop new molecular and computational methods to harness the rapidly-increasing power of next-generation sequencing. Our lab developed Restriction-site Associated DNA (RAD) sequencing, which is being used for trait mapping, creation of genetic maps, phylogeography, association and population structure studies. A variant called RAD paired-end contig sequencing is used to create high-quality genome assemblies by partitioning the sequence reads into manageable groups. We have also developed new methods for rapidly screening populations for mutations, an update to TILLING, and genome-wide methods for assaying enhancer activity.

RAD paired-end contigs are assembled from the randomly sheared fragment ends that sample the region around a restriction site. Sequences sharing a restriction site sequence are assembled into a contig that forgoes many of the problems of whole-genome assembly.

Gene regulation

The response to low oxygen, or hypoxia, involves the regulation of many cellular pathways that shut down low priority cellular activity and increase stress responses. We carry out genome-wide studies to identify genetic targets of hypoxic regulation and how the regulatory network is organized. Using the fruit fly Drosophila as a model system, we have shown that HIF-1, the key transcription factor regulating the response to low oxygen, has connections to many other key signaling pathways in the cell that allow it to orchestrate the cellular response. Hypoxia is an important aspect of the pathology of heart attack and stroke, so understanding the regulatory network gives insight into potential therapeutic targets.

Drosophila tissue culture cells carrying a fluorescent reporter driven by a HIF-1 enhancer from the Heat shock factor gene is turned on by low oxygen stress and requires HIF-1.