Xiang-Ping Chu, M.D., Ph.D.

Associate Professor, Tenured
Department(s) of Biomedical Sciences
Section: Neurosciences
UMKC School of Medicine
816-235-2248
chux@umkc.edu
M4-108
Education and Background

M.S. - Physiology - Fudan University Shanghai Medical College
M.D. - Clinical Medicine - Jiangsu University School of Medicine
Ph.D. - Physiology - Fudan University Shanghai Medical College
Fellowship - Neurobiology - Robert S. Dow Neurobiology Laboratories, Legacy Research Institute

Meet Xiang-Ping Chu
How did you get started in research?

I realized while getting my medical degree that often the reasons for illnesses are hidden, and I wanted to be able to find answers that are not always obvious. After I received my medical degree I was able to do physiology research on opioid receptors at Fudan University in Shanghai and post-doctoral research in Portland, Oregon.

Cellular research seems, in a way, small scale, but doesn’t it have large implications?

Yes, dozens of diseases and illnesses, from anxiety and depression to diabetes and cancer, develop because of defects in the ion channels crucial for regulating cell life and death. And as we understand their role in neurological and psychological diseases, we also discover ways that they can be regulated or modulated. These discoveries offer hope for more effective treatments for stroke, drug addiction, traumatic brain injury and other diseases.

What do you like to do besides research?

I like to spend time with my wife, a lab technician at the Stowers Institute, and our son, whom I used to bring to the lab with me when he was little. I enjoy playing table tennis, often with students at the school of medicine, and fishing with friends on weekends. That is very relaxing. I also am active in a Bible study group and in a Sunday night choir that performs at many events, including Chinese festivals and visits to a retirement center. I am fortunate to have a community of friends with many similar interests.

Biography

Dr. Chu earned his medical degree from Jiangsu University School of Medicine in 1989, and his PhD degree from Fudan University Shanghai Medical College in 1999, both in the People’s Republic of China. He then came to America for postdoctoral training at the Legacy Research Institute in Portland, Oregon in 2000. He received a postdoctoral fellowship from the American Heart Association (AHA) in 2002 and subsequently received a beginning grant-in-aid in 2004 and scientist development grant in 2007, both from the AHA. While at the Legacy Research Institute, Dr. Chu was promoted from research associate to senior research associate, to assistant scientist. In 2008, he was recruited to the UMKC School of Medicine as a tenure-track Assistant Professor to establish an advanced, independent electrophysiology laboratory in a strategic expansion of neuroscience research program.

In 2014, Dr. Chu was promoted to Associate Professor with tenure. His research focuses on the role of ion channels and membrane receptors in the pathogenesis of neurological disorders such as stroke and drug addiction. While at UMKC, his research has been supported by the National Institute of Health (NIH) and the AHA. Dr. Chu teaches medical neuroscience and physiology courses and is a member of UMKC’s doctoral faculty. He has published 3 book chapters and more than 50 peer-reviewed articles with an H-index of 18, and has served as a peer-reviewer for over 30 scientific journals. Dr. Chu currently serves on Editorial Boards for Advances in Neuroscience, International Journal of Physiology, Pathophysiology & Pharmacology (IJPPP), ISRN Physiology, and Scientific Reports. Dr. Chu also serves on grant study sections for the AHA, Medical Research Council of UK, Ataxia Foundation of UK, and the University of Missouri Research Board (UMRB).

Specialties and Research/Medical Interests

Anesthesiology, Neurology, Pediatric Prenatal

Research Focus

Understanding how a particular cell gateway — acid-sensing ion channels, or ASICs — functions and affects everything from stroke, traumatic brain injury and seizures to drug addiction and pain modulation.

Dr. Chu, who came to UMKC in 2008, has received research grants from the National Institute on Drug Abuse, the American Heart Association and the University of Missouri Research Board. His findings have been published in such journals as The Lancet, Cell and Neuron.

Research Summary

One of my research interests is to understand the functional role of ion channels in ischemic brain injury. Brain ischemia induces various biochemical changes, which can activate various ion channels, including Acid-Sensing Ion Channels (ASICs). During hypoxia/ischemia, increased anerobic glycolysis due to the lack of blood and oxygen supply leads to lactic acid accumulation, causing a reduction in pH, and acidosis. For many years, acidosis has been known to play an important role in the pathology of neuronal injury. However, the cellular and molecular mechanisms underlying acidosis-induced injury remain elusive. Recently we have demonstrated that activation of newly described

ASICs contribute to neuronal injury, particularly those containing the ASIC1a subunit. My aim is to explore the potential mechanisms by which ASIC’s are involved in the pathogenesis of ischemic brain injury, particularly the extent to which they might be modulated/regulated by endogenous molecules (e.g. glucose and zinc). ASICs localize to synapses and proton as a neurotransmitter released from synaptic vesicles activates ASICs during neurotransmission. I am also interested in studying the functional role of ASICs in the brain and the interaction between ASICs and other ion channels/receptors (for example, glutamate receptors, dopamine receptors et al.,) during physiological or pathological conditions such as drug abuse. We want to determine whether ASICs play any roles in the pathogenesis of drug abuse or interact with other receptors in the brain in response to psychostimulants.

Mentoring Area

I am interested in mentoring students who have interests in neurological diseases such as drug abuse and ischemic brain injury using a combination of patch-clamp recording, fluorescence-imaging, gene transfection and knockdown, cell injury assay and behavior measurement techniques.

Selected Publications

*Chu XP, Grasing KA, Wang JQ. Acid-sensing ion channels contribute to neurotoxicity. Transl Stroke Res. 5(1):69-78, 2014. *Corresponding author.

Jing L, *Chu XP, *Zha XM. Three distinct motifs within the C-terminus of ASIC1a regulate its surface trafficking. Neuroscience. 247: 321-327, 2013. *Corresponding author.

Jiang Q, Wang CM, Fibuch EE, Wang JQ, *Chu XP. Differential regulation of locomotor activity to acute and chronic cocaine administration in acid-sensing ion channels 1a and 2 in adult mice. Neuroscience. 246C:170-178, 2013. *Corresponding author.

*Chu XP, Xiong ZG. Acid-sensing ion channels in pathological conditions. Adv Exp Med Biol. 961:419-31, 2013. *Corresponding author.

Jiang Q, Zha XM, *Chu XP. Inhibition of human acid-sensing ion channel 1b by zinc. Int J Physiol Pathophysiol Pharmacol4(2):84-93, 2012. *Corresponding author.

Wang JQ, Chu XP, Guo ML, Jin DZ, Xue B, Berry TJ, Fibuch EE, Mao LM. Modulation of ionotropic glutamate receptors and acid-sensing ion channels by nitric oxide. Front Physiol. 3:164, 2012.

*Chu XP, *Jing L,*Jiang YQ, Collier DM, Wang B, Jiang Q, Snyder PM and Zha XM. N-Glycosylation of ASIC1a regulates its trafficking and acidosis-induced spine remodeling. J Neurosci.  32(12):4080-4091, 2012. *These authors contributed equally.

*Chu XP, Xiong ZG. Physiological and pathological functions of acid-sensing ion channels in central nervous system. Curr Drug Targets. 13(2):263-271, 2012. *Corresponding author.

*Chu XP, Papasian CJ, Wang JQ and Xiong ZG. Modulation of Acid-Sensing Ion Channels: Molecular Mechanisms and Therapeutic Potential. Int J Physiol Pharmacol. 3(4):288-308, 2011. *Corresponding author.

Jing L, Jiang Q, Jiang YQ, Chu XP, and Zha XM. Interaction between the first transmembrane domain and the wrist of acid-sensing ion channel 1a is critical for its maturation and trafficking.  PLoS One, 6(10):e26909, 2011.

Jiang Q, Inoue K, Wu X, Papasian CJ, Wang JQ, Xiong ZG, *Chu XP. Cysteine 149 in the extracellular finger domain of ASIC1b subunit is critical for zinc-mediated inhibition. Neuroscience, 193: 89-99, 2011. *Corresponding author.

Duan B, Wang YZ, Yang T, Chu XP, Yu Y, Huang Y, Cao H, Hansen J, Simon RP, Zhu MX, Xiong ZG, Xu TL. Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. J Neurosci. 31: 2101-2112, 2011.

Van Dolah DK, Mao LM, Shaffer C, Guo ML, Fibuch EE, Chu XP, Buch S, Wang JQ. Reversible palmitoylation regulates surface stability of AMPA receptors in the nucleus accumbens in response to cocaine in vivo. Bio Psychiatry. 69: 1035-1042, 2011.

Lin J, Chu XP, Maysami S, Li M, Si H, Cottrell JE, Simon RP, Xiong ZG. Inhibition of acid-sensing ion channel currents by lidocaine in cultured mouse cortical neurons. Anesth Analg. 112:977-981, 2011.

*Chu XP, *Coombes E, *Jiang J, Inoue K, Seeds J, Branigan D, Simon RP, Xiong ZG. Pathophysiological relevant levels of hydrogen peroxide induces glutamate-independent neurodegeneration that involves activation of TRPM7 channels. Antioxid Redox Signal. 14: 1815-1827, 2011. *These authors contributed equally.

Suman A, Mehta B, Guo ML, Chu XP, Fibuch EE, Mao LM and Wang JQ. Alterations in acid-sensing ion channel expression in the rat forebrain following chronic amphetamine administration. Neurosci Res. 68: 1-8, 2010.

Jiang Q, Papasian CJ, Wang JQ, Xiong ZG and *Chu XP. Inhibitory regulation of acid-sensing ion channel 3 by zinc. Neuroscience. 169: 574-583, 2010. *Corresponding author.

*Chu XP, *Mao LM, *Wang W, Zhang GC, Liu XY, Yang YJ, Haines M, Papasian CJ, Fibuch EE, Buch S, Chen JG, Wang JQ. Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine. Nat Neurosci. 12: 602-10, 2009. *These authors contributed equally.

Jiang Q, Li MH, Papasian CJ, Branigan D, Xiong ZG, Wang JQ, *Chu XP. Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum. Neuroscience. 162: 55-66, 2009. *Corresponding author.

Zhang GC, Mao LM, Wang JQ, *Chu XP. Upregulation of acid-sensing ion channel 1 protein expression by chronic administration of cocaine in the mouse striatum in vivo. Neurosci Lett. 459:119-22, 2009. *Corresponding author.

Jiang J, Li MH, Inoue K, Chu XP, Seeds J, and Xiong ZG. TRPM7-like current in human head and neck carcinoma cells: role in cell proliferation. Cancer Res.,67:10929-38, 2007.

Liu X, Chu XP, Mao L, Wang M, Lan H, Li MH, Zhang G, Parelkar NK, Haines M, Neve KA, Liu F, Xiong ZG, and Wang JQ. Modulation of D2R/NR2B interactions in response to cocaine. Neuron, 52, 897-909, 2006.

Chu XP, Close N, Saugstad JA, and Xiong ZG. ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents. J. Neurosci., 26:5329-5339, 2006.

Xiong ZG, *Chu XP, *Zhu XM, Minami M, Hey J, Wemmie JA, Price M, Welsh MJ, and Simon RP.  Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell. 118(6): 687-698, 2004. *These authors contributed equally.

Chu XP, Wemmie JA, Wang WZ, Zhu XM, Saugstad JA, Price MP, Simon RP, Xiong ZG.   Subunit-dependent High-Affinity Zinc Inhibition of Acid-Sensing Ion Channels. J. Neurosci., 24 (40): 8678-8689, 2004.