NIU Department of
Chemistry & Biochemistry
Where the study of matter...matters!
Postdoctoral Fellow, Johns Hopkins University School of Medicine, 2001-2005
Ph.D., Albert Einstein College of Medicine of Yeshiva University, 2001
M.S., Beijing University of Aeronautics and Astronautics, 1990
B.S., Beijing University of Aeronautics and Astronautics, 1987
Organic synthesis; peptide and protein chemistry; protein posttranslational modifications; protein ligand design, synthesis, and characterization; enzymology; medicinal chemistry.
An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Zhang, X.; Gureasko, J.; Shen, K.; Cole, P. A.; Kuriyan, J. (2006) Cell, 125: 1137–1149.
Protein kinase structure and function analysis with chemical tools. Shen, K.; Hines, A. C.; Schwarzer, D.; Pickin, K. A.; Cole, P.A. (2005) Biochim. Biophys. Acta (Proteins & Proteomics), 1754: 65–78.
Conversion of a tyrosine kinase protein substrate to a high affinity ligand by ATP linkage. Shen, K.; Cole, P. A. (2003) J. Am. Chem. Soc., 125: 16172-16173.
Chemical dissection of the effects of tyrosine phosphorylation of SHP-2. Lu, W.; Shen, K.; Cole, P. A. (2003) Biochemistry, 42: 5461-5468.
Protein tyrosine kinases Src and Csk: A tail's tale. Cole, P. A.; Shen, K.; Qiao, Y.; Wang, D. (2003) Curr. Opin. Chem. Biol., 7: 580-585.
The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation. Zhang, Z.; Shen, K.; Lu, W.; Cole, P. A. (2002) J. Biol. Chem., 278: 4668-4674.
Probing the molecular basis for potent and selective PTP1B inhibition. Guo, X.-L.; Shen, K.; Wang, F.; Lawrence, D. S.; Zhang, Z.-Y. (2002) J. Biol. Chem., 277: 41014-41022.
Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial library and screening procedure. Shen, K.; Keng, Y.-F.; Wu, L.; Guo, X.-L.; Lawrence, D. S.; Zhang, Z.-Y. (2001) J. Biol. Chem., 276: 47311-47319.
Research in my laboratory is aimed at applying synthetic organic chemistry and synthetic protein chemistry to the solution of significant biological problems. Specifically, we are interested in protein post-translational modifications in both normal and abnormal cell signaling. These modifications include phosphorylation and dephosphorylation (common modifications of serine, threonine, and tyrosine residues of intracellularly exposed proteins) mediated by protein kinases and phosphatases, and sulfation (an emerging modification of tyrosine residues of extracelluarly exposed and secreted proteins) mediated by tyrosylprotein sulfotransferases.
To investigate these protein modifications, we adopt an interdisciplinary or multidisciplinary approach. With the help of synthetic chemistry and molecular biology, we generate small molecules and protein-based ligands and inhibitors that are targeted toward proteins of interest. With these synthetic or semi-synthetic species as tools, we are then able to investigate the events of protein post-translational modifications in appropriate in vitro and in vivo systems.
These research projects could be tailored to fit into individual interests and provide training ranging from instrumental analysis, organic synthesis, protein chemistry, enzymology, or structural biology to molecular and cellular biology as well.
