Research InterestsMetabolomics, Enzyme Discovery, Pentose Phosphate Metabolism
- Princeton University, Princeton, NJ, U.S., Lewis-Sigler Fellow 2005-2010.
- Washington University School of Medicine, St. Louis, MO, U.S., (with Dr. John P. Atkinson), Research Fellow 2003-2005.
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, U.S., PhD in Biology (with Dr. Gregory Hannon), 1999-2003.
- Washington University, St. Louis, MO, U.S., BA in Biochemistry 1995-1999.
- Department of Molecular Genetics, University of Toronto.
MY RESEARCH OVERVIEW (GO TO SCIENTIFIC OVERVIEW)
Hidden corridors - discovering new metabolic enzymes
The next time you enjoy a meal, take a moment to marvel how your body can digest such a vast array of foods. With the availability of the complete genome sequences of organisms from yeast to man, we now know the full catalogue of genes for each. However, such lists only hint at how organisms process nutrients. Each cell in our bodies must take in nutrients to maintain itself. If so directed by environmental cues, our cells alter their metabolism in order to produce the building blocks necessary to divide. Now, new tools for chemical analysis permit the study of the metabolome, the chemical intermediates of cellular metabolism.
There are two tremendous gaps in our understanding of cell metabolism. First, there are many chemical reactions that are known to occur as cells break down nutrients, yet we do not know the genes that enable these reactions. Second, recent technological advances in mass spectrometry and NMR have detected hundreds of chemicals in cells that are not predicted by our charts of metabolism.
I am working to characterize the chemical reactions carried out by enzymes of unknown function and place them in context of cellular metabolism and disease. Recently, I discovered riboneogenesis, a new metabolic route for the production of ribose, which is a key building block of both our genes (as DNA) and of how those genes are expressed (as RNA). My lab is working to understand the role of riboneogenesis, and to identify other new metabolic pathways.
SCIENTIFIC RESEARCH OVERVIEW
Current projects in the lab include:
1. Enzyme discovery
We combine genetics with metabolomics to continue discovering new enzymes. Past screens in our lab have provided dozens of candidate genes required for normal production of metabolites ranging from nucleosides to compounds not previously observed in biology. Our approaches for metabolomic discovery are also applicable to discovering the mode of action of enzyme inhibitors, and have shed light on the role of nonenzymatic genes as well.
2. Regulation of riboneogenesis
The riboneogenesis pathway provides an alternative flux of carbon from glycolysis to the pentose phosphate pathway. Riboneogenesis does not change the oxidative state of the cell, and we are interested in understanding how cells regulate the activity of the oxidative pentose phosphate pathway, the canonical nonoxidative pentose phosphate pathway, and the riboneogenic pathway to respond to environmental conditions. We combine classic expression analysis with metabolomics to identify genetic and environmental factors regulating the flux of carbon to ribose.
- Broad metabolic sensitivity profiling of a prototrophic yeast deletion collection. VanderSluis B, Hess DC, Pesyna C, Krumholz EW, Syed T, Szappanos B, Nislow C, Papp B, Troyanskaya OG, Myers CL, Caudy AA. Genome Biol. 2014 Apr 10;15(4):R64.
- Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits. Watson E, MacNeil LT, Ritter AD, Yilmaz LS, Rosebrock AP, Caudy AA, Walhout AJ. Cell. 2014 Feb 13;156(4):759-70.
- Riboneogenesis in yeast. Clasquin MF, Melamud E, Singer A, Gooding JR, Xu X, Dong A, Cui H, Campagna SR, Savchenko A, Yakunin AF, Rabinowitz JD, Caudy AA. Cell. 2011 Jun 10;145(6):969-80.
View Pubmed search of Dr. Caudy's full list of publications.