Michael Uhler, Ph.D.
Research Professor, MBNI
Professor, Department of Biological Chemistry

5043 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

muhler@umich.edu

(734) 647-3188

Current Research Interests:

The research in our laboratory has focused on the role of protein kinases in the signal transduction mechanisms that mediate neuronal plasticity. In past studies, we have characterized the protein kinases regulated by cyclic nucleotides and studied the biochemical properties of specific isoforms of these cAMP- and cGMP-dependent protein kinases. Diversity in the biochemical properties of these proteins suggest that the individual isoforms are differentially activated in neuronal cells in response to various stimuli. In addition, we have studied the role of kinase isoforms in the regulation of gene transcription that may form the basis of long term memory. We are currently interested in novel mechanisms for controlling the activity of these protein kinases including specific kinase inhibitor proteins expressed in brain. Future studies will be aimed at characterizing important new physiological substrates phosphorylated by these cyclic nucleotide dependent protein kinases, particularly transcription factors that are able to mediate the changes in gene expression that may be associated with long-term memory.

Our recent research has focused on the use of a novel high throughput transfection method to characterize transcriptional regulation by protein kinases in neurons. The Surface Transfection and Expression Protocol (STEP) allows thousands of transfection reactions to take place on a single microscope slide. We are using expression vectors encoding constitutively active protein kinases together with fluorescent reporter vectors with binding sites for specific transcription factors to identify novel regulatory interactions in neurons. Several new functional interactions have been identified and the biochemical mechansisms responsible for the transcriptional regulation observed are being elucidated.

Selected Publications:

Ren, X and Uhler, M.D. (2009) Microarray transfection analysis of conserved genomic sequences from three immediate early genes. Genomics (in press).

Garber, A.L., Lau, Y.Y., Jordan, D.W., Uhler, M.D. and Gilgenbach, R. M. (2006) Implications of a simple mathematical model to cancer cell population dynamics. Cell Proliferation 39:15-28.

Zhang, L., Duan, C.J., Li, G., Uhler, M.D., Logsdon, C.D. and Simeone, D.M. (2004) A Transforming Growth Factor beta-Induced SMAD3/SMAD4 Directly Activates Protein Kinase A. Mol. Cell Biol. 24:2169-80.

Redmond, T. M., Ren, X., Kubish, G., Atkins, S., Low, S. and Uhler, M.D. (2004) Microarray Transfection Analysis of Transcriptional Regulation by cAMP-dependent protein kinase. Mol. Cell. Proteomics. 38:770-9.

Leinninger, G. M., Backus, C., Uhler, M.D., Lentz, S. I. and Feldman, E. L. (2004) Phosphatidylinositol 3-kinase and Akt effectors mediate insulin-like growth factor-I neuroprotection in dorsal root ganglia neurons. FASEB J. 18(13): 1544-6.