Department of Chemistry and Biochemistry

University of Alaska Fairbanks

PO Box 6160

Fairbanks, AK 99775-6160

(907) 474-5752

fftbk@uaf.edu

Kuhn Homepage

After completing his M.S. in Biochemistry at the University of Zurich, Switzerland, Tom Kuhn received a Ph.D. in Neurobiology from the University of Zurich, Switzerland, in 1992. Following postdoctoral positions at Colorado State University, he was an Assistant Professor at the University of Montana and joined the University of Alaska Fairbanks as an Assistant Professor in 2004.

RESEARCH INTERESTS OF THE KUHN LABORATORY

The primary research of the laboratory aims at understanding the role of Rho-subfamily small GTPases, in particular Rac1A, as pivotal regulators of actin filament dynamics and redox homeostasis in central nervous system (CNS) neurons.  Disruptions of actin filament dynamics and/or redox status are universally associated with acute CNS injuries and many chronic neurodegenerative CNS disorders.  Although axonal growth cones, the tips of elongating axons, are capable of navigating considerable distances prior to establishing connection with their targets during development, they fail to regenerate lost connections following acute axonal injury.  Motility, adhesion, and sensory capacity of neuronal growth cones all reside within filopodia and lamellipodia, two morphological structures located at the leading edge of growth cones.  The dynamics of both filopodia and lamellipodia result from a continuous reorganization of actin filaments in response to growth inhibitory and growth promoting molecular cues.  A strong, progressively spreading inflammation typically follows acute CNS injuries and accompanies many chronic neurodegenerative CNS disorders.  This inflammatory reaction causes severe oxidative damage to cellular proteins and lipids due to an increased production of reactive oxygen species (ROS) and ultimately a loss of the neuronal redox homeostasis.  Key questions we are addressing include the function of Rrac1A in neuronal redox signaling, the identity and regulation of the source of ROS potentially a neuronal NADPH oxidase activity, and antioxidant enzymatic systems in neuronal plasma membranes.  Experimental approaches utilized in the lab include viral mediated gene transfer, state-of-the-art light and fluorescence microscopy techniques, and a broad range of molecular biological and biochemical methods.

A second project addresses neuronal stem cells and their generation, functional integration, and elimination in the adult male wild songbird Junco hyemalis.  During breeding season, several song-specific forebrain nuclei almost double in the number of neurons, which is necessary for the production of song.  We are investigating incorporation, differentiation, and apoptosis of newly generated cells derived from the subependymal ventricular zones with regard to seasonal and hormonal cues.

SELECTED PUBLICATIONS

Kuhn TB, Meberg PJ, Brown MD, Bernstein BW, Minamide LS, Jensen JR, Okada K, Soda EA, and Bamburg JR (2000) Regulating actin dynamics in neuronal growth cones by rho family GTPases and ADF/cofilin. J Neurobiol 44:126-144

Kuhn TB, Brown MD, Wilcox CL, Raper JA, and Bamburg JR (1999) Myelin and collapsin-1 induce motor neuron growth cone collapse through different pathways: inhibition of collapse by opposing mutants of rac1. J Neurosci 19:1965-1975

Kuhn TB, Williams CV, Dou P, and Kater SB (1998) Laminin directs growth cone navigation via two temporally and functionally distinct Ca2+ signals. J Neurosci 18:184-194

Kuhn TB, Schmidt MF, and Kater SB (1995) Laminin and fibronectin signal sustained but opposite effects to passing growth cones. Neuron 14: 1-20

Kuhn TB, Stoeckli ET, Condrau MA, Rathjen FG, and Sonderegger P (1991) Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4). J Cell Biol 11