Professional Overview
Honors and Awards
- NSF-CAREER, National Science Foundation (2007-2012)
- Basil O'Connor Starter Scholar Research Award, March of Dimes (2007-2009)
- Journal Awardee, Synlett/Synthesis (2006)
- Terman Fellowship, Stanford University (2005-2008)
- Research Incentive Grant, Stanford Office of Technology Licensing (2005-2007)
- New Faculty Award, Camille & Henry Dreyfus Foundation (2005)
Scientific Focus
Current Research Interests
Research in my group focuses on understanding and exploiting the molecular foundations of glycoconjugate biosynthesis. Carbohydrates are essential conduits for information transfer in biological systems. Not only are cell surface carbohydrates key arbiters of cell-cell communication but novel roles for protein glycosylation in intracellular processes are also being discovered. In addition, in an era of protein-based therapeutics, specific and efficient glycosylation is an important means of maximizing drugs in vivo efficacies.
In mammalian cells, the organelles of the secretory pathway - the endoplasmic reticulum and the Golgi compartment - orchestrate cell surface glycosylation. The set of carbohydrates synthesized by a cell is determined by the spatial distribution of glycosyltransferases and other modifying enzymes within the Golgi cisternae; this arrangement forms an assembly line for glycoprotein and glycolipid biosynthesis. Accordingly, the collection of carbohydrates displayed on a cells surface provides an extracellular report of the composition and organization of the secretory pathway within that cell.
As a complicated machine responsible for task of glycosylation, the mammalian secretory pathway presents a puzzle to be solved, but also a robust biosynthetic power to be harnessed. One of my labs major research efforts is to obtain a molecular understanding of the processes by which Golgi enzymes select their substrates and coordinate their activities to direct the synthesis of complex carbohydrate structures. We use biochemical and biophysical studies combined with cellular and functional assays to achieve a detailed understanding of how Golgi residents work together to form the glycosylation machinery. Three inter-related questions are paramount: (a) what dictates localization to particular Golgi sub-compartments? (b) is oligomerization required for localization, catalysis, or both? (c) what are the determinants of substrate selectivity?
Parallel to our efforts to understand and discover the inner workings of the secretory pathway, we have also embarked on a program to commandeer this biosynthetic machine to perform novel tasks of our own design. The assembly line architecture of the secretory pathway provides a useful scaffold onto which we will engineer new functionalities. Tools of compelling interest to us are: (a) reprogrammed cell lines whose secretory pathways encode new enzymatic functionality, and (b) new methods to identify glycosylation-dependent protein-protein interactions.
Publications
- Chemical methods for glycoprotein discovery. Curr Opin Chem Biol. 2007; (1): 52-8
- Glycosylation of proteins in the Golgi apparatus Wiley Encyclopedia of Chemical Biology. 2007: in press
- A century at the chemistry-biology interface. Nat Chem Biol. 2006; (6): 288-92
- Regulating cell surface glycosylation with a small-molecule switch. Methods Enzymol. 2006: 213-29
- A small-molecule switch for Golgi sulfotransferases. Proc Natl Acad Sci U S A. 2004; (48): 16715-20
- Directing flux in glycan biosynthetic pathways with a small molecule switch. Chembiochem. 2004; (10): 1455-8
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