The long-term goal of my research is to understand molecular mechanisms and evolution of gene regulation in mammals. I began studying fundamental aspects of chromatin structure as a graduate student, and then moved on to developing methods for isolating genes as molecular clones of genomic DNA as a post-doc with Tom Maniatis. Those early molecular cloning experiments established the technologies and approaches that we now know as genomics. In my lab at Penn State, we built from those initial clones to define the structures and developmental expression of hemoglobin gene clusters in mammals. This work expanded into decades of collaborative research with Webb Miller to rigorously align genomic DNA sequences between species and to use those alignments to illuminate genome evolution and predict gene regulatory regions. Webb and I established a paradigm of molecular biologists and computational scientists working together to define important problems with bioinformatic solutions, developing algorithms that give informative solutions and scale to whole-genome approaches, and experimentally testing hypotheses derived from the bioinformatic analysis to infer the biological meaning of the bioinformatic results. The whole-genome interspecies alignments of genomic DNA developed during this phase are still the backbone for many comparative genomics studies.