Our lab is devoted to studying the molecular mechanisms of major neurodegenerative and/or aging related disorders. The research in our lab has three major directions:
1. Mechanistic study of motor neuron diseases such as SMA and ALS based on patient-specific iPSCs.
We have established multiple lines of patient-specific iPSCs and are trying to build the human cell-based disease models in the petri-dishes. Then we will explore the potential role of synaptopathy and axonopathy in the pathogenesis of these motor neuron diseases. It will be critical to unravel the key molecules that lead to the functional deficits of the motor neurons and the series of signaling events that eventually result in cell death specifically in motor neurons. Toward this end, we are also interested in studying the role of astrocytes in synaptic formation and their role in disease etiology while malfunctioned.
2. The mechanism of DNA damage repair and responses in adult neural stem cells and their regulation during the aging of the adult NSCs.
We will be very interested in studying whether the pool size, the proliferative ability, the ability to handle DNA damage, the differentiation potentials of adult neural stem cells have been changed while the mice get aged. Through some systemic screening approaches, we have identified key molecules such as Sirt1 which may play a critical role in regulating the DDR of adult NSCs. We will use NHEJ and HR GFP reporter system to unravel how Sirt1 regulates the DSB in adult neural stem cells and outline the key signaling pathways. A spectrum of candidate genes such as Ligase 4, KU80, ATM, SMC1A, SMC3 et al, will be studied, respectively, with the same strategy.
3. The third direction of my research interest is toward the cell replacement therapy of neurological diseases.
We have developed the methods to isolate and culture the human ADSCs in large quantity. We are able to trans-differentiate the ADSCs into cortical neurons and motor neurons and transplant these cells into stroke or spinal cord injury models, respectively, to test their efficacy. Beyond the human ADSCs, we are also interested in testing the ES, iPS, MSC, adult NSCs as seed cells and trying to find the best strategy for cell replacement therapy for major neurological diseases such stroke, SCI, PD, SMA, AlS.
Education Background
1995-1999: B.Sc. Peking University
2000-2004: Ph.D. New York Medical College (NYMC)
Positions Held
2004-2005 Postdoctoral Scholar, New York Medical College (NYMC)
2005-2008 Postdoctoral Scholar, UT Southwestern Medical Center \
2008-2009 Chief Scientist ,GSK Shanghai R & D center.
2009 –present Professor of Tongji University
2012-present Vice-Director, Stem Cell Engineering Translational Medicine, Shanghai East Hospital,
Kang S, Zhang Z, Liu X, Manfredsson F, Benskey M, Cao X, Luo H, Xu J*, Sun Y, K Ye*. (2017) a-Synuclein binds and inhibits the TrkB receptors, mediating Dopaminergic neuronal cell death in Parkinson’s disease. PNAS (accepted) (*Corresponding author)
Wang X║, Sun C║, Zhu L, Sun L, Ma R, Wang Z, Lu B*, Chen X*, Xu J*. (2017) Quantitative proteomic analysis revealed changes in protein synthesis and mitochondrial functions after acute DNA damage in mouse neural stem cells. Neurosci Lett. 653:355-361 (*Corresponding author,║equal contribution)
Shi R║, Jin Y║, Cao C, Han S, Shao X, Meng L, Cheng J, Zhang M, Zheng J, Xu J*, Li M*. （2016） Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats Stem Cell Res Ther. 7(1):155 (*Corresponding author,║equal contribution )
Wang X║, Dong C║, Sun L║, Zhu L, Sun C, Ma R, Ning K, Lu B*, Zhang J*, Xu J*. (2016) Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease. Sci Rep. 6:37443. doi: 10.1038/srep37443. (*Corresponding author,║equal contribution )
Gao SE*║, Wang Juan║, Wu ZY, Yuan P, Gao FJ, Zhou F, Cao LM, Chen X, Zhu HW and Xu J* (2015) Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? Autism Open Access, 5(3):151, 2015. (*Corresponding author,║equal contribution )
Zhang WJ║, Wu HX║, Yang M║, Ye SG, Li L, Zhang H, Hu J, Wang XG*, Xu J*, Liang AB* (2015) SIRT1 inhibition impairs non-homologous end joining DNA damage repair by increasing Ku70 acetylation in chronic myeloid leukemia cells. Oncotarget 3. doi: 10.18632/oncotarget.6455. [Epub ahead of print] (*Corresponding author,║equal contribution )
Zhu L║, Dong CM║, Ma RJ, Sun CX, Zhu HW*, Xu J* (2015) Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy. BBRC 464(2):526-33 (*Corresponding author,║equal contribution )
Yang DJ║, Zhu L║, Ren J, Ma RJ, Zhu HW*, Xu J* (2015) Dysfunction of autophagy as the pathological mechanism of motor neuron disease based on a patient-specific disease model. Neuroscience Bulletin 31(4):445-51 (*Corresponding author,║equal contribution )
Zhou F║, Gao S║, Wang L║, Sun CX, Chen L, Li Q, Yuan P, Zhao H, Yi Y, Qin Y, Dong ZY, Cao LM, Ren HY, Zhu L, Ma RJ, Lu B, Liang AB, Xu GT, Zhu HW, Gao ZL, Ma J*, Xu J*, Chen X* (2015). Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model. Stem cell research & therapy 6, 92.
(*Corresponding author,║equal contribution )
Dong CM║, Wang XL║, Wang GM║, Zhu L, Ma RJ, Sun CX, Deng HT, Liang A*, Gao ZL*, Xu J* (2014) A stress-induced cellular aging model with postnatal neural stem cells. Cell death & disease 5:e1116 (*Corresponding author,║equal contribution )
Yang DJ║, Wang XL║, Ismail A, Ashman CJ, Valori CF, Wang G, Gao S, Higginbottom A, Ince PG, Azzouz M, Xu J*, Shaw PJ*, Ning K* (2014) PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons. Cell death & disease 5:e1096. (*Corresponding author,║equal contribution )
Gao S║, Zhao P║, Lin C, Sun Y, Wang Y, Zhou Z, Yang D, Wang X, Xu H, Zhou F, Cao L, Zhou W, Ning K, Chen X*, Xu J* (2013) Differentiation of Human-Adipose Derived Stem Cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds. Tissue engineering Part A 20(7-8):1271-84 (*Corresponding author,║equal contribution )
Shi S║, Gao S║, Cao T, Liu J, Gao X, Hao J, Lv C, Huang H, Xu J*, Yao T* (2013) Targeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+). PloS one 8:e84419. (*Corresponding author,║equal contribution )
Peng H, Kang N, Xu J*, Stanton PK, Kang J* (2013) Two distinct modes of exocytotic fusion pore expansion in large astrocytic vesicles. The Journal of biological chemistry 288:16872-16881. (*Corresponding author )
Hu G, Huang K, Yu J, Gopalakrishna-Pillai S, Kong J, Xu H, Liu Z, Zhang K, Xu J, Luo Y, Li S, Sun YE, Iverson LE, Xue Z, Fan G (2012) Identification of miRNA signatures during the differentiation of hESCs into retinal pigment epithelial cells. PloS one 7:e37224.
Gustavsson N, Wang X, Wang Y, Seah T, Xu J, Radda GK, Sudhof TC, Han W (2010) Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion. PloS one 5:e15414.
Shin OH║, Xu J║, Rizo J, Sudhof TC (2009) Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release. Proceedings of the National Academy of Sciences of the United States of America 106:16469-16474. (║equal contribution)
Xu J, Pang ZP, Shin OH, Sudhof TC (2009) Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nature neuroscience 12:759-766
Xu J, Mashimo T, Sudhof TC (2007a) Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron 54:567-581.
Xu J, Peng H, Kang N, Zhao Z, Lin JH, Stanton PK, Kang J (2007b) Glutamate-induced exocytosis of glutamate from astrocytes. The Journal of biological chemistry 282:24185-24197.
Wu H, Xu J║, Pang ZP║, Ge W║, Kim KJ, Blanchi B, Chen C, Sudhof TC, Sun YE (2007) Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proceedings of the National Academy of Sciences of the United States of America 104:13821-13826. (║equal contribution)
Kang N║, Xu J║, Xu Q, Nedergaard M, Kang J (2005) Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. Journal of neurophysiology 94:4121-4130. (║equal contribution)
Xu J, Kang N, Jiang L, Nedergaard M, Kang J (2005) Activity-dependent long-term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 25:1750-1760.
Xu J, Kang J (2005) The mechanisms and functions of activity-dependent long-term potentiation of intrinsic excitability. Reviews in the neurosciences 16:311-323.
Kang N, Jiang L, He W, Xu J, Nedergaard M, Kang J (2004) Presynaptic inactivation of action potentials and postsynaptic inhibition of GABAA currents contribute to KA-induced disinhibition in CA1 pyramidal neurons. Journal of neurophysiology 92:873-882.
Jiang L, Xu J, Nedergaard M, Kang J (2001) A kainate receptor increases the efficacy of GABAergic synapses. Neuron 30:503-513.
