Timothy M. Gomez
- Professor, Department of Neuroscience
- (608) 263-4554
Ph.D. University of Minnesota
Molecular mechanisms that regulate growth cone motility and guidance
Work in my laboratory focuses on the intracellular mechanisms that control growth cone motility necessary for the proper development of the nervous system. Growth cones are sensory-motor specializations at the tips of all growing axons and dendrites that detect and transduce extracellular cues into guided outgrowth. Mutations in genes involved in the detection and transduction of axon guidance information into directed neurite outgrowth are responsible for many deficits in cognitive function, including autisms, dyslexias, and learning disabilities. By studying the cellular, physiological and molecular mechanisms that govern normal axon outgrowth and guidance, we hope to identify potential sites of therapeutic intervention.
Research in my laboratory combines a variety of fluorescent probe technologies with high resolution live cell fluorescence microscopy to visualize the dynamic behavior of growth cones and assess their physiological responses during axon extension in vitro and in vivo. We use three model systems for our studies. First, we study spinal cord and retinal ganglion cell (RGC) neuron development using the frog Xenopus Laevis due to their large size, rapid development, and ease of molecular and surgical manipulation of embryos. Second, we conduct parallel experiments in vivo using Zebrafish, exploiting the optical clarity of embryos and powerful genetic tools. Finally, we are studying the development of human forebrain, motoneuron and RGCs using neurons derived from human induced pluripotent stem cells (iPSCs). Various gain and loss of function techniques are used to alter the physiology of growth cones both in vitro and in vivo. In addition, we are using iPSCs derived from human patients with various autism spectrum disorders. By combining the latest advances in imaging technologies with improved optical probes including proteins and FRET-based reporter molecules we hope to answer the following questions:
1. What signals regulate the assembly and function of growth cone invadopodia and function downstream of axon guidance cues?
2. How does calcium influx and release through specific channels exert differential affects on neurite outgrowth?
3. What types of mechanosensitive channels are expressed by developing neurons and what roles do they play in axon guidance and regeneration?
4. How does local protein synthesis control axon guidance in human neurons and what roles do autism related genes such as FMRP and TSC have in the control of local protein synthesis downstream of axon guidance cues?Publications:
*Kerstein, P., *Nichol, R., Gomez T.M. (2015) Mechanochemical regulation of growth cone motility. Frontiers in Neuroscience, July 7, 9:244. Pages 1-16.
*Santiago-Medina, M., #Gregus, K. A., *Nichol, R.H. and Gomez, T. M. Regulation of ECM degradation and axon guidance by growth cone invadosomes. Development, Feb 1, 142(3):486-496. Highlighted in Science magazine. Faculty of 1000 selection
Doers M.E., Musser M.T., *Nichol R., Baker M.W., Berndt E.R., Gomez T.M., Zhang S.C., Abbeduto L., Bhattacharyya A. (2014). Induced pluripotent stem cell derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells Dev. March 24. 23 (15): 1777-1787.
*Santiago-Medina, M., #Gregus, K. A. and Gomez, T. M. (2013) PAK-PIX interactions regulate adhesion dynamics and membrane protrusion to control neurite outgrowth. J Cell Science, Mar 1, 126(Pt 5):1122-1133. PMCID: 3635460
*Kerstein, P., *Jacques-Fricke, B., Rengifo, J., Mogen, B., Williams, J., Gottlieb, P., Sachs, F. and Gomez, T. M. (2013) Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth. J Neurosci., Jan 2, 33(1): 273-285. PMCID: 3539200
*Myers, J. P., *Robles, E., #Ducharme-Smith, A. and Gomez, T. M. (2012) Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues. J of Cell Science. Jun, 5;125(Pt 12):2918-2929. PMID: 22393238
*Myers, J. P. and Gomez, T. M. (2011) Focal adhesion kinase promotes integrin adhesion dynamics necessary for chemotropic turning of nerve growth cones. J Neurosci. 21 September; 31(38):13585-13595. PMCID: 3193056
- *Santiago-Medina, M., *Myers, J. P. and Gomez, T. M. (2011) Imaging adhesion and signaling dynamics in Xenopus laevis growth cones. Dev. Neurobio. Apr 4, Epub ahead of print. PMCID: 3158960
*Myers, J. P., *Santiago-Medina, M. and Gomez, T. M. (2011) Regulation of axonal outgrowth and pathfinding by integrin-ECM interactions. Dev. Neurobio. 71 (11): 901-923. PMCID: 3192254
Hengen, K. B., Gomez, T. M. Stang K. M., Johnson, S. M. and Behan, M. (2011). Changes in ventral respiratory column GABAaR e- and d-subunits during hibernation mediate resistance to depression by EtOH and pentobarbital. Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R272-83. PMCID: 3043800
Moon, M-s and Gomez, T. M. (2010) Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo. Mol. Cell. Neurosci. Jun;44(2):118-128. PMCID: 2862809
Woo, S. W., Rowan, D. J. and Gomez, T. M. (2009) Retinotopic mapping requires FAKmediated regulation of growth cone adhesion. J Neurosci. 29(44): 13981-13991. PMCID:2796108
Marriott, G., Mao, S., Sakata, T., Ran, J., Jackson, D. K., Petchprayoon, C., Gomez, T. M., Warp, E., Tulyathan, O., Aaron, H. L., Isacoff, E.Y. and Yan, Y. (2008). Optical lockin detection imaging microscopy for contrast-enhanced imaging in living cells. Proc Natl Acad Sci U S A. 105: 17789-17794. PMCID: 2584753
*NTP Graduate Student
#Neurobiology Undergraduate Student