Background
B.S. in Chemistry, Fairfield University, 2004
Ph.D. in Chemistry, Yale University, 2009, Advisor: Ann M. Valentine
Postdoctoral Research, University of Pennsylvania, 2009-2011, Advisor: David W. Christianson
Research in Biochemistry and Structural Biology
My research uses protein crystallography to study the structure-function relationships of metalloenzymes, namely polysaccharide deacetylases and histone deacetylases. Polysaccharide deacetylases are carbohydrate esterases found in bacteria. These enzymes catalyze the deacetylation of acetylated sugars along the membranes of Gram-positive bacteria, which allows the bacteria to evade host immune systems. Inhibition of these enzymes, therefore, hinders this bacterial defensive mechanism and offers a promising route for the development of new antibiotic therapeutics.
Histone deacetylases catalyze the hydrolysis of acetylated lysine side chains in both histone and non-histone proteins and are implicated in a number of important biological processes. As such, abnormal HDAC activity is linked with various diseases, including many cancers, which makes HDACs validated targets for drug design. In all projects, we are specifically interested in structural information for the design and development of new, potent structure-based inhibitors.
Courses Taught
CHEM 121: Principles of Chemistry (lecture and lab) (Fall)
BIOC 353: Biochemistry: Protein Structure and Function (Fall)
CHEM 325: Experimental Chemistry IV: Advanced Inorganic Chemistry Lab (Spring)
BIOC 481: Current Topics in Biochemistry (senior capstone) (Spring)
CHEM 490: Advanced Elective in Bioinorganic Chemistry (Spring)
Selected Publications
Deardorff, M.A. et al. (2012) HDAC8 Mutations in Cornelia de Lange Syndrome Refine the Cohesin Acetylation Cycle. Nature. in press.
Lombardi, P.M.; Cole, K.E.; Dowling, D.P.; Christianson, D.W. (2011) Structure, Mechanism, and Inhibition of Histone Deacetylases and Related Metalloenzymes. Curr. Opin. Struct. Biol., 21, 735-743.
Cole, K.E.; Dowling, D.P., Boone, M.A.; Phillips, A.J.; Christianson, D.W. (2011) Structural Basis of the Antiproliferative Activity of Largazole, a Depsipeptide Inhibitor of the Histone Deacetylases. J. Am. Chem. Soc., 133, 12474-12477.
Cole, K.E.; Gattis, S.G.; Gennadios, H.A.; Fierke, C.A.; Christianson, D.W. (2011) Structure of the Metal-Dependent Deacetylase LpxC from Yersinia enterocolitica Complexed with the Potent Inhibitor CHIR090. Biochemistry, 50, 258-265.
Cole, K.E.; Valentine, A.M. (2007) Spermidine and Spermine Catalyze the Formation of Nanostructured Titanium Oxide. Biomacromolecules, 8, 1641-1647.
Cole, K.E.; Ortiz, A.N.; Schoonen, M.A.; Valentine, A.M. (2006) Peptide- and Long-Chain Polyamine- Induced Synthesis of Micro- and Nanostructured Titanium Phosphate and Protein Encapsulation. Chem. Mater., 18, 4592-4599.
Cole, K.E.; Valentine, A.M. (2006) Titanium Biomaterials: Titania Needles in the Test of the Foraminiferan Bathysiphon argenteus. Dalton Trans., 3, 430-432.
