Timothy Gomez

RESEARCH INTERESTS –

Work in my laboratory focuses on the intracellular mechanisms that regulate growth cone motility and behavior. Growth cones are sensory-motor specializations at the tips of all growing axons and dendrites that detect and transduce extracellular cues into guided outgrowth.

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, 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 fluorescent fusion proteins and FRET-based reporter molecules we hope to answer the following questions:

1. How does tyrosine kinase signaling by Src and FAK non-receptor tyrosine kinases regulate filopodial protrusion and adhesion dynamics 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 Trp 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.