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Faculty & Research

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Alex Kolodkin

Department Affiliation Primary: Neuroscience
Secondary: Molecular Biology & Genetics
RankProfessor
Phone Numbers410-614-9499
Lab: 410-614-9497
Fax: 410-614-8423
Emailkolodkin@jhmi.edu
School of Medicine Address725 N. Wolfe Street
1001 PCTB
Baltimore MD 21205
Link to Lab Homepage
Alex Kolodkin

Research Topic: Molecular Mechanisms of Neuronal Growth Cone Guidance

Research in my laboratory is focused on understanding how neuronal connectivity is established during development.  Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology, and synapse formation and function.  For several years we have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors.  We employ a cross phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology, and synaptogenesis.  We also seek to understand how these signals are transduced to cytosolic effectors.  Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function.  As a result of the ongoing projects in my laboratory, I and my colleagues have extensive experience in both fly and mouse genetic manipulations and neuroanatomical analysis.  Our current work includes a relatively new interest in understanding the origins of laminar organization in the CNS.  This direction has resulted in our identification of guidance cues that regulate both specific and general aspects of neurite stratification in the mouse retina, in addition to the targeting of retinal ganglion cell axons to retinorecipient midbrain targets.  These observations have prompted us to look for cellular and molecular mechanisms that regulate laminar organization in the mouse neocortex.

Publications:

Sun, L.O., Brady, C.M., Cahill, H., Sakuta, Dhande, O.S., Noda, M., Huberman, A.D., Nathans, J., Kolodkin, A.L.  (2015). Functional assembly of accessary optic system circuitry critical for compensatory eye movements. Neuron. 86, 971-984 [NIHMSID 677901].
PubMed Reference

Riccomagno, M.M., Sun, L.O., Brady, C.M., Alexandropoulos, K., Seo, S., Kurokawa, M., and Kolodkin, A.L. (2014). Cas adaptor proteins organize the retinal ganglion cell layer downstream of integrin signalling. Neuron, 81, 779-786.
PubMed Reference

Sun, L.O., Jiang, Z., Rivlin-Etzion, M., Hand, R., Brady, C.M., Matsuoka, R.L., Yau, K.-W., Feller, M. B., and Kolodkin, A.L. (2013). On and Off retinal circuit assembly by divergent molecular mechanisms.  Science, 342, 1241947; DOI:10.1126/science.1241974 [PMCID In Progress; NIHMSID#: 544230].
PubMed Reference

Jeong, S., Juhaszova, K., and Kolodkin, A.L. (2012). The control of semaphorin-1a-meidated reverse signaling by opposing pebble and RhoGAPp190 functions in Drosophila. Neuron, 140, 627-38.
PubMed Reference
 
Riccomagno, M, Hurtado, A., Wang, H.-B., Macopson, J.G.J., Griner, E.M., Betz, A., Brose, N. Kazanietz, M.G., and Kolodkin, A.L. (2012). The RacGAP b-Chimaerin selectively mediates stereotyped hippocampal axon pruning. Cell.
PubMed Reference
 
Lloyd, T.E., Machamer, J., O’Hara, K, Kim, J.H., Collins, S.E., Wong, M.Y., Sahin, B., Imlach, W., Yang, Y., Levitan, E.S., McCabe, B.D. and Kolodkin, A.L. (2012). The p150/Glued CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Neuron.
PubMed Reference
  

Matsuoka, R.L., Chivatakarn, O, Badea, T.C., Samuels, I.S., Cahill, H., Katayama K, Suto F, Chédotal, A., Peachey, N.S., Nathans, J, Yoshida, Y., Giger, R.J., and Kolodkin, A.L. (2011). Class5 transmembrane semaphorins control mammalian inner retinal lamination, neurite arborization, and function. Neuron 71, 460-473.
PubMed Reference

Matsuoka, R.L., Nguyen-Ba-Charvet, K.T., Parray, A., Badea, T.C., Chedotal, A., and Kolodkin, A.L. (2011). Transmembrane semaphorin signaling controls laminar stratification in the mammalian retina. Nature. 470, 259-263 [doi:10.1038/nature09765].
PubMed Reference 

Wu, Z., Sweeney, L.B. Ayoob, J.C., Chak, K., Andreone, B.J., Ohyama,T. Kerr, R., Luo, L, Zlatic, M., and Kolodkin, A.L. (2011). A combinatorial semaphorin code instructs the initial steps of sensory circuit assembly in the Drosophila CNS. Neuron, 70, 281-298.
PubMed Reference

Tran, T.S., Rubio, M.E., Clem, R.L., Johnson, D.,Case, L.C., Tessier-Lavigne, M., Huganir, R.L., Ginty, D.D., and Kolodkin, A.L. (2009). Secreted Semaphorins Control Spine Distribution and Morphogenesis in the Postnatal CNS. Nature, 462, 1065-9.
PubMed Reference

Huber, A.B., Kania, A., Tran, T.S., Gu, C., De Marco Garcia, N., Lieberam, I., Johnson, D., Jessell, T.M. Ginty, D.D., and Kolodkin, A.L. (2005). Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron 48, 949-964.
PubMed Reference

Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger, R.J., and Kolodkin, A.L. (2004). Semaphorin 5A is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans. Neuron, 44, 961-975.
PubMed Reference

Terman, J.R., and Kolodkin, A.L. (2004). The AKAP Nervy direction couples Protein Kinase A to Plexin-mediated semaphorin repulsion. Science, 303, pp. 1204-1207.
PubMed Reference

Pasterkamp, R.J., Peshon, J.J., Spriggs, M.K. and Kolodkin, A.L. (2003). Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature, 424, pp. 398-405.
PubMed Reference

Giger, R.J., Urquhart, E.R., Gillespie, S.K.H., Levengood, D.V., Ginty, D.D., and Kolodkin, A.L. (1998). Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron, 21, pp.1079-1092.
ScienceDirect

Yu, H.-H., Araj, H.H., Ralls, S.A., and Kolodkin, A.L. (1998). The transmembrane semaphorin Sema-I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron, 20, pp.207-220.
ScienceDirect

Kolodkin, A.L., Levengood, D.V., Rowe, E.G., Tai, Y.-T., Giger, R. J., and Ginty, D. D. (1997). Neuropilin is a semaphorin III receptor. Cell, 90, pp.753-762.
ScienceDirect   

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