- BS, University of California, Santa Cruz, 1997
- Ph.D., Johns Hopkins University, School of Medicine, 2004
- Postdoctoral, University of California, San Francisco, 2010
Honors and Awards
- Paul Ehrlich Research Award, Johns Hopkins University, 2004
- American Cancer Society Postdoctoral Fellowship, 2007
- Biological Sciences Scholar, University of Michigan, 2011
Dan grew up in California and attended UC Santa Cruz (the fighting banana slugs) as an undergraduate, receiving degrees in environmental studies and molecular biology. There he realized his love of science and laboratory research studying prebiotic chemistry and the origins of life under the guidance of David Deamer. With a deepened interest in biochemistry and the molecules and mechanisms that are fundamental to cellular life he attended graduate school at Johns Hopkins University and joined Rachel Green’s lab. There he studied the ribosome, the large RNA:protein complex, universal to all cells and organisms that translates genetic information into protein. For his graduate work Dan focused the translocation step of peptide synthesis - how the tRNA:mRNA machinery ratchets through the ribosome after every peptide bond formation. Using kinetic experiments and in vitro translation assays he discovered that the ribosomal proteins S12 and S13 act as critical control elements during the translocation step while the mechanism of the translocation movement remains inherent to the RNA structure within the ribosome.
With an interest in connecting biochemical methods and structural biology and a newfound desire to visualize macromolecular complexes at the single molecule level, Dan switched focus significantly and joined David Agard’s lab at UCSF to learn electron microscopy. In the Agard lab he gained powerful cryo-EM expertise studying the structure and function of the Hsp90 molecular chaperone. Unique among the chaperone family, Hsp90 plays a critical role in cellular homeostasis and signaling by interacting with substrates in near-native states and promoting refolding and activation events necessary for downstream protein:protein and protein:ligand interactions. Dan achieved several 3-D structures of Hsp90 from different organisms and in different conformational states, identifying a 3-state nucleotide cycle that is universal in E. coli, yeast and human Hsp90s. This work revealed that the Hsp90 cycle involves a conformational equilibrium that is likely tailored to the unique demands of different cellular and substrate environments. Dan also determined the cryo-EM structure of the human Hsp90:Hop complex, identifying a novel substrate loading conformation of Hsp90 and critical regulatory mechanisms of the Hop cochaperone. Dan joined the faculty at the Life Sciences Institute in the Department of Biological Chemistry at U of M in 2011. He continues his focus on cryo-EM methodologies to study the structure and function of molecular chaperone assemblies central to the protein triage process, the molecular ‘decision’ to degrade or activate substrates.