Timothy Gomez

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Great advances have been made in recent years in our understanding of the factors that contribute to guided axon extension. Many new classes of ligands and their receptors have been discovered and we are beginning to appreciate how growth cones integrate multiple extracellular stimuli and convert those signals into stereotyped behaviors.

Research in my laboratory combines a variety of fluorescent probe technologies with confocal and total internal reflection fluorescence (TIRF) microscopy to visualize the dynamic behavior of growth cones and assess their physiological responses during axon extension in vitro and guided outgrowth in the intact spinal cord. We use two model systems for our studies. First, we study spinal cord and retinal ganglion cell (RGC) neuron development using the African Clawed frog Xenopus Laevis due to the large size, rapid development, and ease of molecular and surgical manipulation of its embryos. Second, we are studying the development of human forebrain and motor neurons, as well as photoreceptors 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 fluorescent fusion proteins and FRET-based reporter molecules we hope to answer the following questions:

1. What is the molecular basis for defective axon outgrowth and guidance by developing human neurons with mutations in Tuberous Sclerosis Complex (TSC) genes, TSC1 and TSC2?

2. How do mutations in TSC1 and TSC2 affect dendritic spine development and circuit function by human cortical neurons?

3. What is the molecular basis for human photoreceptor (PR) axon development and how can we promote PR regeneration?

4. What cues regulate growth cone invadopodia formation and function in peripheral axon pathfinding by spinal motor and sensory neurons?

5. What signaling pathways and downstream matrix metalloproteases (MMPs) regulate growth cone invadopodia formation and function?

Selected Publications

• Rempel, S.K., Welch, M.J., Ludwig, A.L., Phillips, J., Kancherla, Y., Zack, D.J., Gamm, D.M., and Gómez, T.M. Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution. Cell Reports, In Press.
• Catlett, T.S., Onesto, M.M., McCann, A.J., Rempel, S.K., Glass, J., Franz, D.N., and Gómez, T.M. (2021) RhoA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex. Nat. Commun. 12(1):2589.
• Nichol RH 4th, Catlett TS, Onesto MM, Hollender D, Gómez TM. (2019) Environmental Elasticity Regulates Cell-type Specific RHOA Signaling and Neuritogenesis of Human Neurons. Stem Cell Reports. Dec 10;13(6):1006-1021.
• Kerstein PC, Patel KM, Gomez TM (2017) Calpain-Mediated Proteolysis of Talin and FAK Regulates Adhesion Dynamics Necessary for Axon Guidance.  J Neurosci. 2017 Feb 8;37(6):1568-1580.
• Nichol RH 4th, Hagen KM, Lumbard DC, Dent EW, Gómez T.M. (2016) Guidance of Axons by Local Coupling of Retrograde Flow to Point Contact Adhesions. J Neurosci. Feb 17;36(7):2267-82. PMID: 26888936.
• Short CA, Suarez-Zayas EA, Gomez TM.(2016) Cell adhesion and invasion mechanisms that guide developing axons. Curr Opin Neurobiol. Aug;39:77-85. PMID: 27135389.
• Santiago-Medina, M., Gregus, K. A., Nichol, R.H. and Gomez, T. M. (2015). Regulation of ECM degradation and axon guidance by growth cone invadosomes. Development, Feb 1, 142(3):486-496.
• Doers ME, Musser MT, Nichol R, Baker MW, Berndt ER, Gomez TM, Zhang SC, 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. Epub ahead of print.
• Gomez, T. M. and Letourneau, PC. (2014). Actin dynamics in growth cone motility and navigation. J Neurochem, Oct 24. Epub ahead of print.
• 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, Jan 15, Epub ahead of print.
• 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. PMID: 23283340
• 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
• 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. 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
• 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
• 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