个人简介
Robert Kennedy is the Willard Professor of Chemistry and Professor of Pharmacology at the University of Michigan. Professor Kennedy earned a B.S. in Chemistry at the University of Florida (1984) and a Ph.D. from the University of North Carolina (1988). He was a post-doctoral fellow at North Carolina from 1989-1991. He became professor of chemistry at the University of Florida in 1991 and served there for 11 years before moving to Michigan. He teaches undergraduate courses in analytical chemistry and a graduate course on Chemical Separations. His research interests are analytical chemistry and its application to neuroscience, endocrinology, and biotechnology. His group has developed instrumentation that couples sampling probes to capillary electrophoresis, capillary chromatography, mass spectrometry, and microfluidic assays for monitoring neurotransmitters in vivo. These methods have been used for studying changes in neurotransmitter concentrations associated with behavior and diseases. His group has also developed sensors and microfluidic devices for monitoring insulin secretion from pancreatic b-cells. These methods are coupled with metabolomics to understand the biochemical mechanism of insulin secretion and perturbations associated with diabetes. His group is also researching use of rapid electrophoretic and mass spectrometric assays as novel approaches to high-throughput screening. His work has been recognized by several awards including two MERIT awards from the NIH, a Presidential Faculty Fellowship, a Sloan Foundation Fellowship, Beckman Young Investigator Award, ACS Findeis Award, McKnight Award for Technical Innovations in Neuroscience, and Golay Award for Achievements in Chromatography. He has held several service posts and is presently Associate Editor of Analytical Chemistry and Director of the Microfluidics in Biomedical Sciences Training Program at Michigan.
研究领域
Analytical Chemistry/Bioanalytical Chemistry/Bioinorganic Chemistry/Chemical Biology/Optics and Imaging/Sensor Science/Nanoscale analytical techniques/Chemical separations/Mass spectrometry/Microfluidics/Neurochemistry/Islet Biology
Our primary goal is to develop nanoscale analytical techniques and explore their use in the measurement of neurotransmitters and hormones both in vivo and at single cells. This goal requires development of techniques capable of measuring zeptomole (10-21 mole) quantities in chemically complex nanoliter samples.
For in vivo measurements, we are coupling capillary zone electrophoresis (CZE) and capillary liquid chromatography (LC) with in vivo sampling methods. The sampling probes continuously remove samples which are periodically and automatically injected into the separation column. In one project, we have developed a 1 s CZE separation of several neurotransmitters which allows high resolution monitoring of neurotransmitter activity. Another project, just underway, involves combining capillary LC with mass spectrometry to discover novel neurotransmitters.
In the area of single cell analysis, we have focused on development of microsensors and confocal fluorescence microscopy for measurement of insulin secreted from cells with millisecond resolution. We are also pursuing analytical methods that allow simultaneous detection of intracellular messengers such as Zn2+, Ca2+, oxygen, and glucose at the same cells. The combination of these methods will provide a complete chemical picture of the cell as it functions.
As we begin to understand the dynamics of extracellular signaling molecules, it also becomes important to understand the intracellular chemical changes that result from the interaction of such molecules with receptors. To facilitate these studies, we are developing techniques based on capillary electrophoresis, fluorescence detection, and mass spectrometry to detect and modern intracellular signal transduction. Applications include detection of G-proteins, proteins with SH2 domains, and phosphorylated proteins. Such measurements can be considered directed proteomics measurements.
All of these techniques involve development of novel analytical chemistry as well as instrumentation. Recently, a significant effort has been made in developing microfabricated instruments for micro-total analytical systems (mu TAS) to perform the analyses described above. In addition to the fundamental analytical work, application of these methods to studies of brain and endocrine function as well as diseases such as diabetes and Alzheimer's are underway in various collaborations.
近期论文
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Patterson CM, Wong JM, Leinninger GM, Allison MB, Mabrouk OS, Kasper CL, Gonzalez IE, Mackenzie A, Jones JC, Kennedy RT, Myers MG Jr. “Ventral tegmental area neurotensin signaling links the lateral hypothalamus to locomotor activity and striatal dopamine efflux in male mice.“ Endocrinology. 2015.
Cepeda DE, Hains L, Li D, Bull J, Lentz SI, Kennedy RT. “Experimental evaluation and computational modeling of tissue damage from low-flow push-pull perfusion sampling in vivo.“ J Neurosci Methods. 2015. 242C:97-105.
Flak JN, Patterson CM, Garfield AS, D’Agostino G, Goforth PB, Sutton AK, Malec PA, Wong JM, Germani M, Jones JC, Rajala M, Satin L, Rhodes CJ, Olson DP, Kennedy RT, Heisler LK, Myers MG Jr. “Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative energy balance.“ Nat Neurosci. 2014. 17(12):1744-50.
Kuo S, Zhou Y, Kim HM, Kato H, Kim RY, Bayar GR, Marcelo CL, Kennedy RT, Feinberg SE. “Biochemical indicators of implantation success of tissue-engineered oral mucosa.“J Dent Res. 2015. 94(1):78-84.
Guetschow ED, Steyer DJ, Kennedy RT. “Subsecond electrophoretic separations from droplet samples for screening of enzyme modulators.“ Anal Chem. 2014, 86(20):10373-9.
Vander Weele CM, Porter-Stransky KA, Mabrouk OS, Lovic V, Singer BF, Kennedy RT, Aragona BJ. “Rapid dopamine transmission within the nucleus accumbens: dramatic difference between morphine and oxycodone delivery.“ Eur J Neurosci. 2014, 40(7):3041-54.
Sun S, Kennedy RT. “Droplet electrospray ionization mass spectrometry for high throughput screening for enzyme inhibitors.“ Anal Chem. 2014, 86(18):9309-14
Dugan CE, Cawthorn WP, MacDougald OA, Kennedy RT. “Multiplexed microfluidic enzyme assays for simultaneous detection of lipolysis products from adipocytes.” Anal Bioanal Chem. 2014, 406(20):4851-9
El-Azzouny M, Evans CR, Treutelaar MK, Kennedy RT, Burant CF. “Increased Glucose Metabolism and Glycerolipid Formation by Fatty Acids and GPR40 Receptor Signaling Underlies the Fatty Acid Potentiation of Insulin Secretion.” JOURNAL OF BIOLOGICAL CHEMISTRY. 2014, 289(19):13575-13588
Bosse KE, Jutkiewicz EM, Schultz-Kuszak KN, Mabrouk OS, Kennedy RT, Gnegy ME, Traynor JR. “Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism.” NEUROPHARMACOLOGY. 2014, 77:19-27
Dugan CE, Kennedy RT. “ Measurement of Lipolysis Products Secreted by 3T3-L1 Adipocytes Using Microfluidics.” METHODS OF ADIPOSE TISSUE BIOLOGY, Book Series: Methods in Enzymology. 2014, 538:195-209
Mabrouk OS, Semaan DZ, Mikelman S, Gnegy ME, Kennedy RT. “Amphetamine stimulates movement through thalamocortical glutamate release.” JOURNAL OF NEUROCHEMISTRY. 2014, 128(1):152-161
Nie J, Kennedy RT. “Capillary liquid chromatography fraction collection and postcolumn reaction using segmented flow microfluidics.” JOURNAL OF SEPARATION SCIENCE. 2013, 36(21-22):3471-3477
Rauch JN,Nie J,Buchholz TJ,Gestwicki JE,Kennedy RT. “Development of a Capillary Electrophoresis Platform for Identifying Inhibitors of Protein-Protein Interactions.” Analytical Chemistry. 2013, 85(20):9824-9831
Kennedy RT. “Emerging trends in in vivo neurochemical monitoring by microdialysis.” CURRENT OPINION IN CHEMICAL BIOLOGY. 2013, 17(5):860-7
Davda D, El Azzouny MA, Hernandez JL, Majmudar JD, Kennedy RT, Martin BR. “Profiling Targets of the Irreversible Palmitoylation Inhibitor 2-Bromopalmitate.” ACS CHEMICAL BIOLOGY. 2013, 8(9):1912-7
Jin S, Anderson GJ, Kennedy RT. “Western blotting using microchip electrophoresis interfaced to a protein capture membrane.” Analytical Chemistry. 2013, 85(12):6073-9.
Zhou Y, Mabrouk OS, Kennedy RT. “Rapid Preconcentration for Liquid Chromatography-Mass Spectrometry Assay of Trace Level Neuropeptides.” Journal of American Society Mass Spectrometry 2013 Apr 17. [Epub ahead of print]
Lee WH, Slaney TR, Hower RW, Kennedy RT. “Microfabricated sampling probes for in vivo monitoring of neurotransmitters.” Analytical Chemistry 2013, 85(8):3828-31.
Akiyama M, Liew CW, Lu S, Hu J, Martinez R, Hambro B, Kennedy RT, Kulkarni RN. “X-Box Binding Protein 1 Is Essential for Insulin Regulation of Pancreatic α-Cell Function.” Diabetes. 2013, 62(7):2439-49.