Professor of Chemistry and Biological Chemistry
About
My laboratory is interested in novel mechanisms of enzyme catalysis, enzyme regulation and designing self-assembling proteins. Our current research projects focus on enzymes that catalyze carboxylation and decarboxylation of aromatic molecules, which may provide routes to green commodity chemicals. We are also studying the regulation and interactions of enzymes involved in the cellular antiviral response. Lastly, we are developing strategies for the assembly of proteins into nano-cages. Our research is inherently inter-disciplinary and draws on a synergistic combination of bio-organic, bio-inorganic and bio-physical chemistry. We are fortunate to enjoy numerous productive collaborations with other research groups at Michigan.
Enzymes for green chemical production
The design of highly efficient, environmentally friendly methods for producing commodity chemicals and biofuels requires engineering new metabolic pathways, which, in turn, requires new enzymes. We are currently studying a recently discovered class of enzymes that catalyze (de)carboxylation reactions on otherwise unreactive aromatic molecules. Despite their potentially useful applications, these enzymes are poorly understood in terms of their catalytic properties, which hinders attempts to engineer them into new biochemical pathways. We are using a variety of techniques to study the mechanisms of these enzymes and engineer them towards new substrate specificities.
Enzymes that fight viruses
Cells have most likely been fighting infection by viruses from the beginning of life. Viperin is one of the most ancient enzymes involved in the cellular antiviral response; it is conserved in all kingdoms of life and is strongly upregulated in response to viral infections. Despite this, viperin was only recently discovered to catalyze the synthesis of a novel antiviral nucleotide that blocks viral replication in a manner similar to many antiviral drugs. In simple organisms, this is probably all viperin does, but in higher animals, including humans, viperin interacts with many different proteins to coordinate a multifaceted response to viral infection. It is these regulatory interactions that we are focused on characterizing to better understand viperin’s unique role in the cell’s innate immune response.
Self-assembling protein nano-cages
The assembly of individual protein subunits into higher order (quaternary) structures is a ubiquitous feature of biology and essential for the biological function of many proteins. The proteins are remarkably diverse in their structures and functions, which suggests that assembling proteins into new, large-scale supramolecular structures will provide a powerful approach for the construction of novel, responsive biomaterials. We have developed a simple, symmetry-based approach to assemble proteins into nano-cages with defined geometries and stoichiometries that is largely independent of the structural details of the protein fold. One important and useful property that emerges from assembling such protein cages is enhanced protein stability. We are currently focused on understanding the assembly pathway to elucidate what features of the design that contribute to efficient assembly and enhanced stability.
Research Areas
- Bioinorganic Chemistry
Bioorganic Chemistry
Biophysical Chemistry
Chemical Biology
Energy Science
Nano Chemistry
Organic Chemistry
Enzyme mechanisms
Protein engineering and design
Awards
- Chair, Faculty Senate, University of Michigan 2018 - 2019
- Fellow, American Association for the Advancement of Science, 2017
- Fellow, Royal Society of Chemistry, 2005
- Royal Society University Research Fellow 1990 - 1995
- Doctor of Science, University of Cambridge
