Department of Neurobiology
Room 2.138B Medical Research Building
Route: 1069 | Tel: (409) 772-6708 | Email: kaechang@utmb.edu
Lab Website
Education and Training
Postdoctoral training, University of California, San Francisco, Mentor: Jonah Chan
Ph.D. in Developmental Biology, Baylor College of Medicine, Mentor: Matthew Rasband
M.S. in Microbiology and Immunology, National Yang-Ming University, Taiwan, Mentor: Soo-Chen Cheng
B.S. in Life Science, National Tsing Hua University, Taiwan, Mentor: Jui-Chou Hsu
Research Interests
More than trillions of nerve impulses are generated every second in our nervous system as part of the communication between neurons and their downstream targets. These electric signals, or action potentials, are propagated along the axons of neurons.
In jawed vertebrates like us, many axons are wrapped in an insulating coating composed of compact glial membranes, called myelin. Myelination is one of the greatest evolutionary advances that facilitated the development of our complex nervous
system. Myelin increases action potential conduction velocity while simultaneously decreasing energy and space demands. However, the breakdown of myelin in pathological or injury conditions disrupts nervous system function and causes a wide range
of neurological deficits, including motor, sensory, and cognitive impairment. Our long-term research goal is to obtain a deep understanding of the molecular mechanisms of myelination and the biology of myelin-making glial cells--oligodendrocytes
in the central nervous system and Schwann cells in the peripheral nervous system. This will provide essential pieces of information for developing therapeutic strategies to repair myelin and restore neurological functions of patients.
Rapid saltatory conduction requires the polarization of myelinated axons into distinct molecular domains. For example, paranodal junctions flank nodes of Ranvier at the gaps between myelin sheaths, and both nodes and paranodes contain molecular domains
essential for proper functioning of myelinated axons. We recently discovered that an RNA-binding protein TDP-43 in myelinating glia regulates, through the repression of a cryptic exon, the expression of the cell adhesion molecule neurofascin,
which is required for the assembly and maintenance of paranodal junctions. When TDP-43 is ablated in Schwann cells, neurofascin and paranodal junctions are lost, causing a 50% nerve conduction delay and motor deficits in mice. This revealed a
previously unknown molecular link where the master gene regulator TDP-43 in Schwann cells regulates neuron-glia interactions and polarization of myelinated axons.
Rapid saltatory conduction also depends on the proper morphological parameters of myelin sheaths, including their thickness and length. We are currently investigating a special class of membrane-remodeling proteins, which participate in shaping oligodendroglial
myelination.
Myelination is essential for proper nervous system function, and “proper” myelination is crucial for optimal nerve conduction and our daily activity, such as sensing the world and making a decision. How is proper myelination achieved during
development and through adaptive myelin remodeling by life experience? Understanding these mechanisms and knowing how to harness them will be required for manipulating glial cells to enhance and accelerate nervous system repair in the future.
Selected Publications
Chang KJ, Agrawal I, Vainshtein A, Ho WY, Xin W, Tucker-Kellogg G, Susuki K, Peles E, Ling SC#, Chan JR#. (2021) TDP-43 maximizes nerve conduction velocity by repressing a cryptic exon for paranodal junction assembly in Schwann cells.
eLife 10, e64456.
Susuki K, Zollinger DR, Chang KJ, Zhang C, Huang CY, Tsai CR, Galiano MR, Liu Y, Benusa SD, Yermakov LM, Griggs RB, Dupree JL, Rasband MN. (2018) Glial βII spectrin contributes to paranode formation and maintenance. J Neurosci 38, 6063-75.
Petersen MA, Ryu JK*, Chang KJ*, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme CA, Wu MD, Rios Coronado PE, Meyer-Franke A, Yahn S, Pous L, Lee JK, Schachtrup C, Lassmann H, Huang
EJ, Han MH, Absinta M, Reich DS, Ellisman MH, Rowitch DH, Chan JR, Akassoglou K. (2017) Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells and inhibits remyelination after vascular damage. Neuron 96, 1003-12.
*Equal contribution
Chang KJ, Redmond SA, and Chan JR. (2016) Remodeling myelination: implications for mechanisms of neural plasticity. Nat Neurosci 19, 190-97.
Zollinger DR, Chang KJ, Baalman K, Kim S, and Rasband MN. (2015) The polarity protein Pals1 regulates radial sorting of axons. J Neurosci 35, 10474-84.
Chang KJ, and Rasband MN. (2015) Cell surface protein-protein binding on COS-7 cells. Bio Protoc 4, e1020.
Frischknecht R, Chang KJ, Rasband MN, and Seidenbecher CI. (2014) Neural ECM molecules in axonal and synaptic homeostatic plasticity. Prog Brain Res 214, 81-100.
Chang KJ, Zollinger DR, Susuki K, Sherman DL, Makara MA, Brophy PJ, Cooper EC, Bennett V, Mohler PJ, and Rasband MN. (2014) Glial ankyrins facilitate paranodal axoglial junction assembly. Nat Neurosci 17, 1673-81.
Ho TS, Zollinger DR, Chang KJ, Xu M, Cooper EC, Stankewich MC, Bennett V, and Rasband MN. (2014) A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier. Nat Neurosci 17, 1664-72.
Chang KJ, and Rasband MN. (2013) Excitable domains of myelinated nerves: axon initial segments and nodes of Ranvier. Curr Top Membr 72, 159-92.
Susuki K*, Chang KJ*, Zollinger DR, Liu Y, Ogawa Y, Eshed-Eisenbach Y, Dours-Zimmermann MT, Oses-Prieto JA, Burlingame AL, Seidenbecher CI, Zimmermann DR, Oohashi T, Peles E, and Rasband MN. (2013) Three mechanisms assemble central nervous
system nodes of Ranvier. Neuron 78, 469-82. *Equal contribution
Galiano MR*, Jha S*, Ho TS, Zhang C, Ogawa Y, Chang KJ, Stankewich MC, Mohler PJ, and Rasband MN. (2012) A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly.
Cell 149, 1125-39.
Gasser A*, Ho TS*, Cheng X, Chang KJ, Waxman SG, Rasband MN, and Dib-Hajj SD. (2012) An ankyrinG-binding motif is necessary and sufficient for targeting Nav1.6 sodium channels to axon initial segments and nodes of Ranvier.
J Neurosci 32, 7232-43.
Chang KJ*, Susuki K*, Dours-Zimmermann MT, Zimmermann DR, and Rasband MN. (2010) Oligodendrocyte myelin glycoprotein does not influence node of Ranvier structure or assembly. J Neurosci 30, 14476-81. *Equal contribution
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