Faculty

Our research is in the field of bioanalytical chemistry. We are interested in identifying problems of biological interest and then developing appropriate analytical techniques to address those problems. Students may be involved in methods or instrument development, application to biological problems, or both depending upon their interests. Techniques utilized in the laboratory include: capillary electrophoresis, capillary chromatography, mass spectrometry, confocal imaging, microfluidics, and sensors. These techniques are applied to studies of: signal transduction and biological recognition, in vivo neurochemical signaling (especially as it relates to addiction), and insulin secretion. A key feature of our group is the use of nanoscale measurements that allow detection of attomole or zeptomole quantities of material in complex mixtures.

Signal transduction and biological recognition. Intracellular chemistry is organized and controlled by affinity interactions. We have developed unique tools based on high-speed electrophoresis that allow quantification of these interactions between ligand-receptor, peptide-protein, and protein-protein. We are using these tools presently in studies of G protein coupled receptor signal transduction and SH2 domain-phosphoprotein transduction to address questions of interaction specificity, structure effects on affinity, and effects of drugs on these interactions.

In vivo neurochemistry. The brain utilizes over 200 compounds as neurotransmitters. These chemicals are released in specific brain regions in response to environmental, pharmacological, and internal effects. Imbalance or inappropriate release of transmitters is associated with mental illnesses such as addiction and depression. We have developed a unique approach to monitor the release of these transmitters in vivo in behaving animals. This allows us to evaluate the dynamics of neurotransmission in vivo under experimental conditions. Numerous studies related to addiction are presently underway in collaboration with groups in psychiatry, psychology, and pharmacology.

Insulin Secretion. β-cells in the pancreas secrete insulin in response to elevated glucose. Impairment of this process is a hallmark of type 2 diabetes; however, the precise biochemical mechanism of glucose-stimulated insulin secretion remains unknown. We have developed techniques based on sensors, microfluidics, and imaging to monitor insulin secretion, metabolism in real-time. We are using these tools to uncover chemical mechanisms of oscillatory insulin secretion, insulin-regulation of secretion, and mitochondrial signals for secretion.

Awards

Fellow of the American Association for the Advancement of Science
American Microchemical Society’s Benedetti-Pichler Memorial Award, 2001
NSF Award for Special Creativity, 1999-2001
Denise Desty Memorial Award for Most Innovative Paper in Separations, 1998
ACS Findeis Award in Analytical Chemistry, 1998
NSF Presidential Faculty Fellow, 1996-1998
Alfred P. Sloan Fellow, 1995-1997
Lilly Analytical Research Fellow, 1994-1995
Beckman Young Investigator Award, 1994-1996
NSF National Young Investigator Award, 1993-1996

Representative Publications

1. Haskins, W.E., Cellar, N.A., Watson, C.J., Powell, D. and Kennedy, R.T., "Discovery and Screening of Peptides in Vivo by Chemical Analysis of Microdialysis Samples", Analytical Chem., 2004, 76(18), 5523.

2. Roper, M.G., Shackman, J., Dahlgren, G. and Kennedy, R.T., "Microfabricated Chip for Chemical Monitoring of Live Cells", Analytical Chem., 2003, 75, 4711.

3. Jameson, E.E., Cunliffe, J, Neubig, R.R., Sunahara, R. and Kennedy, R.T., "Detection of G Proteins by Affinity Probe Capillary Electrophoresis Using a Fluorescently Labeled GTP Analogue", Analytical Chem., 2003, 75, 4297.

4. Gee, K., Qian, W.J. and Kennedy, R., "A novel Zn2+ Selective Fluorophore and Application to Pancreatic ?-cells", J. Am. Chem. Soc., 2002, 124, 776.

5. Kennedy, R.T., Kauri, L. and Dahlgren, G., "Metabolic Oscillations in Pancreatic ß-cells", Diabetes, 2002, 51, S152.

6. Aspinwall, C.A., Qian, W., Roper, M., Kahn, C.R., Kulkarni, R. and Kennedy, R.T., "Roles of Insulin Receptor Substrate-1, Phosphatidyl-inositol-3-kinase, and Release of Intracellular Ca2+ in Insulin-stimulated Insulin Secretion", J. Biol. Chem., 2000, 275, 22331.