My early scientific work emphasized determining, interpreting, and comparing complete sequences of mitochondrial and chloroplast genomes of phylogenetically diverse animals, plants, and eukaryotic microorganisms. My lab has determined the complete mtDNA sequences of ~200 species and of cpDNA sequences of ~100 species. The results addressed questions of genome evolution, deep evolutionary relationships, intron evolution, post-transcriptional modification of tRNAs, gene movements among intracellular compartments, changes in the genetic code, and the evolution of codon usage patterns.
From 2000-2007, I was the Head of Evolutionary Genomics and part of the six-person Senior Management Team of the DoE Joint Genome Institute (JGI), one of the world’s largest genome sequencing centers, with an annual budget at the time of $65 million. I led their transition from being a human genome sequencing facility to being a comparative genomics institute and JGI is, today, broadly acknowledged as premier among such institutes in its sampling of phylogenetically diverse organisms and in their evolutionary comparisons. I led the development of the $20 million/year “JGI Community Sequencing Program” that provides genomic data to the scientific community through peer review.
In 2007, I left full-time employment at the University of California (of which JGI is a part) and reduced my appointment at JGI to that of a “guest researcher” (while maintaining an appointment as adjunct professor at UC Berkeley) to establish a corporation called Genome Project Solutions, Inc. that would provide genome sequencing, interpretations, and database, software, and visualization tools to clients, both corporate and academic.
In one or another of these positions, I have led numerous whole genome sequencing projects, including those of the crustacean Daphnia pulex (chosen, then, by NIH as an officially designated model organism), the butterfly Danaus plexippus, the mollusk Potamopyrgus antipodum, the glaucophyte Cyanophora paradoxa, the moss Physcomitrella patens, the stramenopile alga Nannochloropsis gaditana, the green alga Chlorella vulgaris, and the oömycetes Phytophthora sojae and P. ramorum, and performed major parts of the analyses for the genomes of the fish Xiphophorus maculatus, the tunicate Ciona intestinalis, the mollusk Lottia gigantea, the annelids Helobdella robusta and Capitella teleta, and the oömycetes Pythium ultimum and Hyaloperonospora arabidopsidis.
My work has made significant contributions to understanding the genome duplications at the base of the vertebrates, the evolutionary transfer of genes among intracellular compartments, modes of genome rearrangement, mammalian sex chromosome evolution, and Hox gene cluster evolution, recognizing regulatory elements in DNA sequences, using genome-level characters for reconstructing evolutionary relationships, evaluating changes in gene expression patterns, understanding the effects of various genome processes on DNA sequence evolution, and identifying the genomic underpinnings of plant pathogenesis and environmental adaptation, crop improvement, biofuels production, responses to environmental challenges, behavioral complexity, asexuality within lineages, and differential longevity among populations.
Two examples of software created by my group include, first, DOGMA (“Dual Organellar Genome Annotator”), which provides a semi-automated tool for identifying and annotating genes for mitochondrial and plastid genomes that is in common usage. Second is PHRINGE (“Phylogenetic Resources for the Interpretation of Genomes”), which accepts the complete gene sets of many genomes, clusters these into families using a unique algorithm, creates true phylogenetic trees for each cluster, and has an extensive set of databases, displays, and queries for comparing homologous genes across these genomes. This has been shown to be the most accurate method for assigning gene function based on inference of homology, the only possible evidence in the absence of genetic or biochemical experimentation. PHRINGE was also used to demonstrate much more robustly than any other study the reality of the two rounds of whole genome duplication that characterized the origin of the vertebrates. The paper reporting that study is in the top 1% of all cited articles ever published in the high-profile journal PLoS Biology.
In 2015, I decided to refocus my career on biomedicine and spent all of 2016 in a “sabbatical-like” experience here at the Institute for Systems Biology. At the beginning of 2017, I was hired as the Director of Scientific Technology for Providence St. Joseph Health, reporting to Lee Hood in his capacity as PSJH Senior Vice President and Chief Science Officer, and my responsibilities include forming and managing strategic partnerships among PSJH clinicians and researchers, building outside collaborations, implementing technology for translational medicine, to include high-throughput genomics, proteomics, and single cell assays, leading an independent, externally-funded research program, and interfacing with the broader scientific community.
In total, I have led 23 governmental grant-funded projects totaling over $12 million. In the process, scores of students, postdoctoral scholars, and visiting researchers have been trained. I have published 119 scientific manuscripts, 12 of which were in either Nature or Science and six were in Proceedings of the National Academy of Sciences. These works have been cited, collectively, more than 23,000 times, over 11,000 of these within the last five years, and have an “h-index” of 71, meaning that 71 of these papers have been cited at least 71 times each.
Systems Biology; Genomics; Biotechnology; Bioinformatics; Evolutionary Biology; Genetics; Biomedicine
Ph.D., Biology, University of Michigan, Ann Arbor, Michigan
B.S., Biology, Pennsylvania State University, State College, Pennsylvania