Douglas A. Andres
Professor
B.S. University of Wisconsin, Madison
Ph.D. Purdue University
dandres@pop.uky.edu
859-257-6775

Research Interests  |  Selected References  |  PubMed

Regulation of Neuronal Survival by the Rit and Rin GTPases.

PICTURES: Neurite outgrowth/RNAi effect on neurite/Fly eye-wing picture

Aberrant cell death (apoptosis) contributes to various neurodegenerative disorders including stroke, epilepsy, and Alzheimer's disease. Elaborating the signal transduction mechanisms that regulate neuronal survival is thus important for understanding both basic biology and for therapeutic intervention. Neurotrophins (nerve growth factors) potently stimulate neuronal survival in part by activating members of the Ras small GTP-binding protein family, which function to translate and direct neurotrophin-initiated signals into multiple signaling pathways. We have discovered a novel, evolutionarily conserved group of Ras-related proteins (Rit and Rin) that are regulated by neurotrophins and direct neural pro-survival signaling cascades. Through the combined use of biochemistry, molecular biology, and genetic approaches, we continue to examine the function of these unique regulators of neuronal survival with the goal of applying this knowledge toward the treatment of neurodegenerative disease.

Publications:

Spencer M., Shao, H., Tucker, H.M., and Andres D.A. (2002) NGF-dependent activation of the small GTPase Rin. J. Biol. Chem. 227, 17605-15.

Spencer, M., Shao, H. and Andres, D.A. (2002) Induction of neurite outgrowth in pheochromocytoma cells by the     Rit             GTPase. J. Biol. Chem. 277, 20160-68.

Hynds, D.L., Spencer, M.L., Andres. D.A., and Snow, D.M. (2003) Rit promotes MEK-independent neurite branching in             human neuroblastoma cells. J. Cell Sci. 116(10),1925-35.

 Shi, G. –X and Andres, D.A. (2005) Rit Contributes to NGF-Induced Neuronal Differentiation via Activation of B-Raf-ERK and p38 MAP kinase Cascades. Mol. Cell. Biol. 25(2), 830-846.

 Harrison, S.M.W., Rudolph, J.L., Spencer, M.L., Wes, P.D., Montell, C., Andres, D.A., and Harrison, D.A.   (2005) Activated RIC, a small GTPase, genetically interacts with the Ras pathway and calmodulin during Drosophila development. Developmental Dynamics, 232(3), 817-826.