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Wolfe Hall

Room 1235
Phone: 419.530.2065
Fax: 419.530.7737

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Du, Jianyang

 Deborah Chadee

Assistant Professor

Office Location: WO3205B

Email: jianyang.du@utoledo.edu

Laboratory Webpage:http://dujianyang.wixsite.com/dulab-utoledo

REsearch

Protons have been a proposed neurotransmitter for decades. Yet only recently has solid evidence emerged to support this claim (Du J et al., 2014; Highstein SM et al., 2014). Extracellular protons in the brain are an important signaling messenger involved in neuronal functions. More importantly, numerous neurological diseases such as ischemia, seizure, multiple sclerosis and neurodegenerative diseases all generate acidosis. Understanding how protons signal not only helps us to better understand neuronal physiology but also has important implications in their roles in diseases. Acid-sensing ion channels (ASICs) are proton receptors. Their localization and pH sensitivity put them in an ideal position to sense small pH changes at the synaptic cleft and elsewhere in the neuron. ASICs are important in multiple aspects of peripheral and central neuronal functions. ASICs have been implicated in aspects of behavior and memory including fear-related learning and memory.

The long-term goal of my lab is to understand how protons regulate brain circuits and behaviors. Ultimately, this focus will lead to the development of novel therapeutic targets for treating emotional disorders such as anxiety, depression, post-traumatic stress disorder (PTSD) and schizophrenia. We believe that our current and future work will significantly impact the field of neuroscience by addressing the following important questions:

1. How do protons function as a neurotransmitter to control synaptic transmission in the brain? Addressing this question in a multidisciplinary fashion will significantly contribute to the understanding of the how neurotransmission occurs and is modified by protons.

2. How do protons amend and reshape neural circuits? How does this affect subsequent behavior(s)? One of the fundamental questions in neuroscience is how do neural circuits drive and modify behaviors. Illuminating how protons regulate neural circuits will provide insight into this complex and challenging area.

3. Can protons and their receptors function as a new therapeutic target for the treatment of neurological illnesses? The major proton receptors, ASICs have been suggested as targets for many neuronal diseases, including anxiety, depression, seizure, stroke and Parkinson’s disease, etc.. Developing therapeutics targeting proton signaling may therefore significantly benefit many individuals and improve the quality of life for hundreds of thousands of people. One of our ongoing projects, Acid-sensing ion channel 1a contributes to synaptic transmission and plasticity in ischemia, has been funded by American Heart Association.

Current STudents

Juthika Mandal - Ph.D. student
Md Zubayer Hossain Saad - Research Assistant
Kritika Singh - Undergraduate

Current laboratory grants

AHA SDG 15SDG25700054 2015 - 2018
Acid sensing ion channel 1a contributes to synaptic transmission and plasticity in ischemia

publications

Du J*, Reznikov LR, Welsh MJ. Expression and Activity of Acid Sensing Ion Channels in the Mouse Pituitary. PLoS ONE 9(12):e115310. Corresponding author.

Du J, Reznikov LR, Price MP, Zha XM, Lu Y, Moninger TO, Wemmie JA, Welsh MJ. (2014). Protons function as a neurotransmitter in regulating synaptic transmission and plasticity in the amygdala. Proc Natl Acad Sci U S A. 111(24):8961-6.

Du J, Xie J, Zhang Z, Tsujikawa H, Fusco D, Silverman D, Liang B, Yue L. (2010). TRPM7 mediated Ca2+ signal and cardiac fibroblast differentiation in atrial fibrillation patients. Circ Res. 106(5):992–1003.

Du J, Xie J, Yue L. (2009). Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proc Natl Acad Sci U S A. 106(17):7239-44.

Du J, Xie J, Yue L. (2009). Modulation of TRPM2 by acidic pH and the underlying mechanisms for pH sensitivity. J Gen Physiol. 134(6):471-88.

Li M *, Du J *, Jiang J, Ratzan W, Su LT, Runnels LW, Yue L. (2007). Molecular determinants of Mg2+ and Ca2+ permeability and pH sensitivity in TRPM6 and TRPM7. J Biol Chem. 282(35): 25817-30. (* co-first author).

Zuo WL*, Du JY *, Huang JH *, Li S, Zhang G, Chen SL, Ruan YC, Cheng CH, Zhou WL. (2010). Tyrosine phosphorylation modulates store-operated calcium entry in cultured rat epididymal basal cells. J Cell Physiol. 226(4):1069-73. (* co-first author).

Du JY, Zuo WL, Ruan YC, Yang ZH, Chen MH, Chen SL, Li S, Wu ZL, Xiang H, Zhou WL. (2009). Stimulating Effects of Dopamine on Chloride Transport Across the Rat Caudal Epididymal Epithelium in Culture. Biol Reprod. 80(1):13-23.

Du JY, Ruan YC, Zuo WL, Yang ZH, Chen MH, Wu ZL, Xiang H, Zhou WL. (2006). Cellular mechanisms of carbachol-stimulated Cl- secretion in rat epididymal epithelium. Biol Reprod. 75(3):407-13.

Du JY, Zuo WL, Chen MH, Xiang H, Zhou WL. (2006). Involvement of muscarinic acetylcholine receptors in chloride secretion by cultured rat epididymal epithelium. Cell Biol Int. 30(9):741-6.

Kreple CJ, Lu Y, Taugher RJ, Schwager-Gutman AL, Du J, Stump M, Wang Y, Fan R, Sowers LP, Radley JJ, LaLumiere RT, Welsh MJ, Wemmie JA. Acid-sensing ion channel 1A in the nucleus accumbens regulates drug reward behavior and contributes to synaptic transmission and plasticity. Nat Neurosci. 2014 Aug;17(8):1083-91.

Reznikov LR, Dong Q, Chen JH, Moninger TO, Park JM, Zhang Y, Du J, Hildebrand MS, Smith RJ, Randak CO, Stoltz DA, Welsh MJ.(2013). CFTR-deficient pigs display peripheral nervous system defects at birth. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3083-8.

Vralsted VC, Price MP, Du J, Schnizler M, Wunsch AM, Ziemann AE, Welsh MJ, Wemmie JA. (2011). Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning. Genes Brain Behav. 10(4):444-50.

Yue Z, He Y, Xie J, Stock J, Du J, Yue L. The role of TRP channels in cardiovascular system. Am J Physiol Heart Circ Physiol. 2015 Feb 1;308(3):H157-82.

 Xie J, Sun B, Du J, Yang W, Chen HC, Overton JD, Runnels LW, Yue L. (2011). Phosphatidylinositol 4,5-bisphosphate (PIP(2)) controls magnesium gatekeeper TRPM6 activity. Sci Rep. 2011;1:146.

Heeringa SF, Möller CC, Du J, Yue L, Hinkes B, Chernin G, Vlangos CN, Hoyer PF, Reiser J, Hildebrandt F (2009). A novel TRPC6 mutation that causes childhood FSGS. PLoS ONE. 4(11): e7771.

 Xiang H, Wang L, Cui J, Du J, Wang K, Xu A. (2009). Effects of recombinant neurotoxins on single Na(+) channels in isolated rat hippocampal neurons. J Biochem Mol Toxicol. 23(4):244-55.

Ruan YC, Wang Z, Du JY, Zuo WL, Guo JH, Zhang J, Wu ZL, Wong HY, Chung YW, Chan HC, Zhou WL. (2008). Regulation of smooth muscle contractility by the epithelium in rat vas deferens: role of ATP-induced release of PGE2. J Physiol. 586(Pt 20):4843-57.

Chen M, Du J, Jiang W, Zuo W, Wang F, Li M, Chan H, Zhou W. (2008). Functional expression of cystic fibrosis transmembrane conductance regulator in rat oviduct epithelium. Acta Biochim Biophys Sin. 40(10): 864-72.

Yang ZH, Yu HJ, Pan A, Du JY, Ruan YC, Ko WH, Chan HC, Zhou WL. (2008). Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. PLoS ONE. 3(10): e3348

Zhou WL, Zuo WL, Ruan YC, Wang Z, Du JY, Xiong Y, Chan HC. (2007). The role of extracellular ATP in the male reproductive tract. Sheng Li Xue Bao. 59(4):487-494

Zhang L, Tang SB, Xiang H, Du JY, Huang B, Luo Y, Chen XG. (2007). Effect of supernatant fluid of retinal cells on dynamics of sodium ion channels of neuron-like cells derived from embryonic stem cells. Chin J Ocul Fundus Dis. 23: 91-93

Zhong XF, Li YP, Ge J, Huang B, Peng FH, Du JY, Lin JX, Wu ZL, Liu JB. (2006). Isolation and culture of tumor stem cells in human retinoblastomas. Chinese Journal of pathophysiology. 22(6):1177-1181

Ou J, Wang L, Ding X, Du J, Zhang Y, Chen H, Xu A. (2004) Stationary phase protein overproduction is a fundamental capability of Escherichia coli. Biochem Biophys Res Commun. 2004 Jan 30;314(1):174-80.

Wang L, Ou J, Peng L, Zhong X, Du J, Liu Y, Huang Y, Liu W, Zhang Y, Dong M, Xu AL. (2004). Functional expression and characterization of four novel neurotoxins from sea anemone Anthopleura sp. Biochem Biophys Res Commun. 2004 Jan 2;313(1):163-70.

Last Updated: 10/24/16