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个人简介

Education BChE, Chemical Engineering, University of Dayton MS, Biology, University of Dayton PhD, Biochemistry, University of Illinois Post Doctoral Fellow, Structural Biology, University of Pennsylvania Post Doctoral Fellow, Structural and Cancer Biology, University of North Carolina

研究领域

Research in my laboratory focuses on important problems in signal transduction pertinent to human health. Our approach is interdisciplinary, combining, biochemical, biophysical, cell biological and molecular biology methods to gain insight into the mechanisms governing signal transduction in eukaryotic and prokaryotic systems. The major goal is to elucidate the molecular mechanisms that regulate signal transduction. Our recent work has focused on two systems. The first system involves the Rho family of GTPases, a subfamily of the well known Ras superfamily. In their active state, Rho GTPases interact with effector proteins to coordinate changes in gene expression and the actin cytoskeleton. Several molecules, including guanine exchange factors (GEFs), regulate the active state of Rho GTPases. Importantly, the aberrant function of GEFs has been associated with developmental anomalies, mental retardation, and human disease. The long-term goal of this research is to understand the detailed molecular mechanism(s) by which GEF proteins regulate the activation of Rho-family GTPases and how their deregulation leads to disease. The second system centers on bacterial chemosensory in the soil bacterium Myxococcus xanthus. Chemosensory in Myxococcus xanthus is essential for developmental gene expression, biofilm formation, intercellular communication and gliding motility. In collaboration with Dr. John Kirby (U of I, Microbiology) we are elucidating the biochemical and structural basis for Myxococcus xanthus chemosensory signaling.

近期论文

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Liu, X., Speckhard, D. C., Shepherd, T. R., Sun, Y. J., Hengel, S. R., Yu, L., Fowler, C. A., Gakhar, L. & Fuentes, E. J. (2016). Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions.. Structure (London, England : 1993), 24(12), 2053-2066. DOI: 10.1016/j.str.2016.08.019. Darnell, C., Wilson, J., Tiwari, N., Fuentes, E. & Kirby, J. (2014). Chemosensory regulation of a HEAT-repeat protein couples aggregation and sporulation in Myxococcus xanthus. J Bacteriol, 196(17), 3160-8. DOI: 10.1128/JB.01866-14. Liu, Y., Collins, C., Kiosses, W. B., Murray, A. M., Joshi, M., Shepherd, T. R., Fuentes, E. J. & Tzima, E. (2013). A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. The Journal of cell biology, 201(6), 863-73. Liu, X., Shepherd, T. R., Murray, A. M., Xu, Z. & Fuentes, E. J. (2013). The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure (London, England : 1993), 21(3), 342-54. Joshi, M., Gakhar, L. & Fuentes, E. J. (2013). High-resolution structure of the Tiam1 PHn-CC-Ex domain. Acta crystallographica. Section F, Structural biology and crystallization communications, 69(Pt 7), 744-52. Willett, J. W., Tiwari, N., Muller, S., Hummels, K. R., Houtman, J. C., Fuentes, E. J. & Kirby, J. R. (2013). Specificity residues determine binding affinity for two-component signal transduction systems. MBio, 4(6), e00420-13. Shepherd, T. R., Fuentes, E. J. (2011). Structural and thermodynamic analysis of PDZ-ligand interactions. Methods in enzymology, 488, 81-100. Shepherd, T. R., Hard, R. L., Murray, A. M., Pei, D. & Fuentes, E. J. (2011). Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains. Biochemistry, 50(8), 1296-308.

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