Dan Herschlag

Stanford University


Primary Section: 21, Biochemistry
Secondary Section: 29, Biophysics and Computational Biology
Membership Type: Member (elected 2018)

Biosketch

Dan Herschlag is a biochemist known for deep and creative investigation of molecular and atomic behavior of RNA and proteins, and for his dedication to the development and support of students and young scientists. He has defined how molecular properties define and delineate biological function and evolution, developing the RNA Chaperone hypothesis of the concept of Catalytic Promiscuity. He was born in White Plains, New York, and grew up outside of Peekskill, New York. He began college studying math at the University of Michigan and, after spending time traveling, returned to study at SUNY Binghamton where he received a degree in Biochemistry in 1982. After spending a year at the University of Minnesota Dan pursued graduate work at Brandeis University with W.P. Jencks, where he received his PhD in Biochemistry in 1988. He began postdoctoral research in RNA catalysis with Tom Cech at the University of Colorado in 1989 and joined the faculty at Stanford’s Department of Biochemistry in 1992, where he has remained. In addition to his research teaching, Dan has served in many formal and informal roles in support of students and postdocs, including as Senior Associate Dean of Graduate Education and Postdoctoral Affairs (2011-2015), where he initiated many innovative programs.

Research Interests

The overarching goal of my lab has been to develop understanding of the chemical and physical principles that underlie biological processes in order to understand how biology works, how it evolved, and how the fundamental physical and chemical properties of biomolecules enable and constrain evolution and biological function. We take an interdisciplinary approach, spanning and integrating physics, chemistry and biology, and employing a wide range of techniques, and we are particularly interested in questions of how enzymes work, both protein and RNA, how RNA folds, how proteins recognize RNA, and the roles of RNA/protein interactions in regulation and control, and the evolution of molecules and molecular interactions. Our research has led to discoveries and new directions in enzyme and RNA research, including the RNA Chaperone hypothesis; the evolutionary and mechanistic concept of Catalytic Promiscuity; pioneering genomic studies with Pat Brown that revealed global regulation and organization of gene expression by RNA binding proteins; the first FRET-based single-molecule folding experiments with Steve Chu; kinetic and thermodynamic frameworks for ribozyme catalysis and dissection of the roles of metal ions; kinetic and thermodynamic dissection of RNA folding pathways and development of the Reconstitution Model for RNA folding; determination of the interrelationship between hydrogen bond structure, environment, and energetics; identification of new catalytic mechanisms such as aromatic-anion interactions to position enzymatic general bases and ground state electrostatic destabilization.

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