Bill Chiu

Mitochondria supply energy to maintain health of the nervous system. Our laboratory is interested in how mitochondrial dysfunction contributes to neurodegenerative diseases. In normal neurons, mitochondria are targeted to dendritic, axonal and synaptic compartments to maintain proper signaling in brain network. We are interested in how mitochondria are targeted to various neuronal compartments, and how inappropriate targeting contributes to pathology. Currently we are interested in the role of a key anchoring protein, Syntaphilin (SNPH), in the demyelinating disease multiple sclerosis (MS). MS is the most devastating of all demyelinating diseases in the US, affecting 10-20 per 100,000. MS typically has two phases: early Relapsing-Remitting MS (RRMS) with robust inflammation that transitions into a Secondary Progressive MS (SPMS) with subdued inflammation. Progressive MS poses the single most important treatment challenge to MS: once MS converts into the progressive phase, neurodegeneration essentially becomes irreversible and resists virtually all approved FDA treatments. The key to treating late phase MS lies in the elucidation of a non-inflammatory mechanism for killing nerve tissues. Using animal models for Progressive MS, we discovered that excessive anchoring of mitochondria by SNPH underlies neuronal death and that genetic knockout of SNPH leads to dramatic neuroprotection. Our ultimate goal is to design a therapeutic treatment for Progressive MS by targeting SNPH to unclog damaging congestion of mitochondria in this terminal phase of MS.

Selected Publications

• Joshi DC, Zhang CL, Babujee L, Vevea JD, August BK, Sheng ZH, Chapman ER, Gomez TM, Chiu SY (2019) Inappropriate Intrusion of an Axonal Mitochondrial Anchor into Dendrites Causes Neurodegeneration. Cell Reports 2019 Oct 15;29(3):685-696.
• Lu, Y., Fujioka, H., Joshi, D., Li, Q., Sangwung, P., Hsieh, P., Zhu, J., Torio, J., Sweet, D., Wang, L., Chiu, S. Y., Croniger, C., Liao, X., & Jain, M. K. (2018). Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge. Scientific reports, 8(1), 8251.
• Sechi, M., Lall, R. K., Afolabi, S. O., Singh, A., Joshi, D. C., Chiu, S. Y., Mukhtar, H., & Syed, D. N. (2018). Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models. Scientific reports, 8(1), 15726.
• Huang, G., Massoudi, D., Muir, A. M., Joshi, D. C., Zhang, C. L., Chiu, S. Y., & Greenspan, D. S. (2017). WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial Fusion. Cell reports, 20(4), 923–934.
• Joshi DC, Zhang CL, Lin TM, Gusain A, Harris MG, Tree E, Yin Y, Wu C, Sheng ZH, Dempsey RJ, Fabry Z, Chiu SY (2015) Deletion of Mitochondrial Anchoring Protects Dysmyelinating Shiverer: Implications for Progressive MS. J. Neurosci. 35(13):5293-5306.
• Khan, M. I., Adhami, V. M., Lall, R. K., Sechi, M., Joshi, D. C., Haidar, O. M., Syed, D. N., Siddiqui, I. A., Chiu, S. Y., & Mukhtar, H. (2014). YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin. Oncotarget, 5(9), 2462–2474.
• Zhang CL, Rodenkirch L, Schultz JR, Chiu SY (2012) A novel method to study the local mitochondrial fusion in myelinated axons in vivo. J Neurosci Methods. May 30;207(1):51-8.
• Chiu SY (2011) Matching Mitochondria to Metabolic Needs at Nodes of Ranvier. Neuroscientist Aug 17(4):343-50.
• Zhang, C.L., Ho, P.L., Kintner, D.B., Sun, D. and Chiu, S.Y., (2010) Activity-dependent regulation of mitochondrial motility by calcium and na/k-atpase at nodes of ranvier of myelinated nerves. J Neurosci. 30: 3555-66
• Zhang, C.L., Wilson, J.A., Williams, J. and Chiu, S.Y., (2006) Action potentials induce uniform calcium influx in mammalian myelinated optic nerves. Journal of Neurophysiology. 96: 695-709
• Zhang, C.L., Messing, A. Chiu, S.Y. (1999) Specific Alteration of Spontaneous GABAergic inhibition in cerebellar Purkinje cells in mice lacking the potassium channel Kv1.1. J. Neurosci. April 15, 19(8).
• Zhou, L., Messing, A. and Chiu, S.Y., (1999) Determinants of excitability at transition zones in kv1.1-deficient myelinated nerves. J Neurosci 19: 5768-81
• Chiu, S.Y., Shrager, P. & Ritchie, J.M. (1994). Neuronal-type Na+ and K+ channels in rabbit cultured Schwann cells. Nature. 311: 156-157.
• Kriegler, S. & Chiu, S. Y. (1993). Calcium signaling of glial cells along mammalian axons. J. Neurosci 13: 4229-4245.
• Jensen, A. M. & Chiu, S. Y. (1990). Fluorescence measurement of changes in intracellular calcium induced by excitatory amino acids in cultured cortical astrocytes. J. Neurosci. 10: 1165-1175.
• Chiu, S. Y. & Wilson, G. F. (1989). The role of potassium channels in Schwann cell proliferation in Wallerian degeneration of explant rabbit sciatic nerves. J. Physiol. 408: 199-222.
• Chiu, S.Y. & Ritchie, J.M. (1980). Potassium channels in nodal and internodal axonal membrane of mammalian myelinated fibre. Nature 284: 170-171.
• Chiu, S.Y., Ritchie, J.M., Rogart, R.B. & Stagg, D. (1979). A quantitative description of membrane currents in rabbit myelinated nerve. J. Physiol. 292: 149-166.