Dalby, Kevin

Kevin N Dalby

Professor
College of Pharmacy

Johnson & Johnson Centennial Professor in Pharmacy


dalby@austin.utexas.edu

Phone: 512-471-9267

Office Location
BME 6.202B

Postal Address
The University of Texas at Austin
College of Pharmacy
1 University Station A1900
Austin, TX 78712

Cancer is most commonly caused by the development of aberrant cell signaling pathways. Modern pharmaceutical research thus seeks a clear understanding of these pathways in efforts to treat this all too prevalent illness. A major focus in our laboratory is ERK, a striking mitogen-activated protein kinase that regulates cellular processes with remarkable efficiency and specificity. MAP kinases are mediators of numerous cellular signals, and are believed to play major roles in tumor formation and progression to metastasis. The mitogenic pathway most important in the pathogenesis of human cancer contains the Ras–>Raf–>MEK–>ERK module. Students with an interest in integrating the disciplines of chemistry and biochemistry in the search for treatment of human disease are strongly encouraged to join us by applying. We employ a chemical-biology approach in efforts to elucidate the biochemical basis for the regulation and mechanism of protein kinases. Using state-of-the-art enzyme kinetic techniques we have uncovered surprising mechanisms of substrate recognition. We are currently applying structural methods to address some of the questions posed by these studies. Using high through-put screening, coupled to chemical and peptide library approaches, we are developing small molecule and peptide inhibitors of protein kinases. These inhibitors will be used to elucidate the roles of kinases in cancer progression. The potential for cancer treatment through the targeting of protein kinase remains largely untapped. Our laboratory endeavors to identify these treatments by utilizing novel efforts in chemical biology.

Assignment of Backbone Resonances in a Eukaryotic Protein Kinase – Inactive ERK2 as an Illustrative Example (2012) Methods Mol Biol. 831, 359-68.

Nonvisual Arrestins Function as Simple Scaffolds Assembling the MKK4-JNK3α2 Signaling Complex. (2011) Biochemistry 50, 10520-9.

Examining docking interactions on ERK2 with modular peptide substrates. (2011) Biochemistry 50, 9500-10.

The Effect of Arrestin Conformation on the Recruitment of c-Raf1, MEK1, and ERK1/2 Activation. (2011) PLoS One, e28723.

93 nm Photodissociation of Singly and Multiply Charged Peptide Anions for Acidic Proteome Characterization, (2011) Proteomics, 1329-34.

Understanding the Specificity of a Docking Interaction between JNK1 and the Scaffolding Protein JIP1 (2011) journal of Physical Chemistry 115, 1491-502.

Virtual Screening Using Molecular Simulations (2011) PROTEINS: Structure, Function, and Bioinformatics 79, 1940-51.

MODEL OF A MAPK•SUBSTRATE COMPLEX IN AN ACTIVE CONFORMATION: A COMPUTATIONAL AND EXPERIMENTAL APPROACH (2011) PLoS One 6, e18594.

SOLUTION NMR INSIGHTS INTO DOCKING INTERACTIONS INVOLVING INACTIVE ERK2. (2011) Biochemistry 50, 3660-72.

Development of JNK2-Selective Peptide Inhibitors that Inhibit Breast Cancer Cell Migration. (2011) ACS Chem. Biol. 6, 658-66.

Activated ERK2 is a Monomer in vitro with or without Divalent Cations and when Complexed to the Cytoplasmic Scaffold PEA15 (2011) Biochemistry 50, 4568-78.

Purification and Characterization of Tagless Recombinant Human Elongation Factor-2 Kinase (eEF-2K) Expressed in Escherichia coli (2011) Protein Expression and Purification 79, 237-44.