Chengbiao Wu 

Chengbiao Wu 

Associate Professor

 

Contact Information

Phone: 858-534-0996
Fax: 858-534-4782

Mailing Address:
9500 Gilman Drive # 0649
La Jolla, CA 92093-0649

Lab website 


Chengbiao Wu earned his Ph.D. in Molecular Biology from Queen’s University in Kingston, Ontario, Canada in 1994. After earning his Ph.D. he completed postdoctoral appointments with the prestigious NHLBI in the Lab of Cell Biology at the NIH in Bethesda, MD., the University of Texas Southwestern Medical Center, and Stanford University.

Dr. Wu’s research in the molecular and cellular basis of neuronal dysfunction is an integral part of the Neuroscience research program. His research focuses on understanding the molecular and cellular mechanisms of neurotrophin signaling in health and disease.

Neurotrophic factors (NTFs) are small proteins that support the survival and maintenance of nerve cells. Many types of neurodegenerative diseases such as Down syndrome, Alzheimer’s disease and Huntington disease are linked to insufficient supply of NTFs. He is discovering how neurotrophin signals are generated and transduced in nerve cells and how defective neurotrophin signaling pathways lead to neurodegenerative diseases.

His work has been published in top journals such as the Journal of Neurosciences and PNAS and has received recognition from prominent investigators in the field of neurotrophin signaling. Dr. Wu has contributed to over a dozen papers exploring and extending the signaling endosome concept in NGF signaling.

Dr. Wu is a founding member of the Down Syndrome Center for Research and Treatment at UCSD, serving as the Director of Cellular and Molecular Biology.

Axons are the primary target in many central and peripheral neurophathies. Dysfunction and degeneration of axons i.e. axonopathy is often the earliest sign of neurodegeneration. We use molecular, cellular, biochemical, and imaging methods to investigate the molecular mechanisms of axonopathy and neurodegeneration in both the central and peripheral nervous system. Our ultimate goal is to understand how axonal dysfunction contributes to neurodegenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD), Down syndrome (DS), and Charcot-Marie-Tooth 2B (CMT2B).

Using both in vitro and in vivo models, we have demonstrated that retrograde axonal transport of neurotrophic factor signals play a critical role in supporting neuronal survival and function. We have uncovered that 1) a single nerve growth factor (NGF) dimer is sufficient to induce internalization of NGF and its receptor, TrkA; 2) sustained NGF signals mediated by Rap1 are initiated at the axonal terminal and are carried during their transit within axons to the cell body in Rab5-decorated early endosomes; and 3) the molecular motor protein, dynein, is required for retrograde trafficking of NGF signaling. We have also developed novel methods for producing biologically active neurotrophic factors labeled with one biotin/protein. The reagent is crucial for imaging axonal transport of neurotrophic factors such as brain-derived neurotrophic factor (BDNF).

We are actively developing cutting-edge technologies to pursue novel hypotheses regarding axonopathy. Our current projects are focused on: 1) Impact of mutant huntingtin in Huntington’s disease on axonal trafficking and signaling of BDNF; 2) Molecular and cellular Mechanisms of sensory neuropathy caused by mis-sense mutations of Rab7 in human CMT2B; 3) Study of signaling and trafficking of a “painless” mutant form NGF and its potential use in treating neurodegenerative diseases; 4) Role of HSP90 in regulating axonal trafficking and signaling of neurotrophic factors. The central theme of our projects is to define the molecular and cellular events by which axonal function is compromised under neurodegenerative conditions, and ultimately we aim to identify the best avenue(s) to prevent axonopathy and restore neuronal function.

Illustration:
http://lh6.ggpht.com/_RIjx_Mg4ZVM/TNv7yiH0WUI/AAAAAAAAC2s/5U9Fg4y5Ebo/s1600-h/image3.png

2015

April M. Weissmiller, Orlangie Natera-Naranjo, Sol M. Reyna, Matthew L. Pearn, Xiaobei Zhao, Phuong Nguyen, Soan Cheng, Lawrence S.B. Goldstein, Rudolph E. Tanzi, Steven L. Wagner, William C. Mobley and Chengbiao Wu. 2015. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: Evidence for a role for APP. PLoS One. 2015 Feb 24;10(2):e0118379.

2014

Sarah H. Shahmoradian, Mauricio R. Galiano, Chengbiao Wu, Shurui Chen4, Matthew N. Rasband, William C. Mobley, Wah Chiu. Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography. Published on Feb 12, 2014. Journal of Visualized Experimements (JoVE) 50783

Xiaobei Zhao, Yue Zhou, April M. Weissmiller, Matthew L. Pearn, William C. Mobley, Chengbiao Wu. Real-time Imaging of Axonal Transport of Quantum dot-labeled BDNF in Primary Neurons. In press. Journal of Visualized Experiments (JoVE).

2013

Xin Wang, Yingjun Zhao, Xiaofei Zhang, Hedieh Badie,Ying Zhou,Yangling Mu, Li Shen Loo, Lei Cai, Robert C Thompson, Bo Yang, Yaomin Chen, Peter F Johnson, Chengbiao Wu, Guojun Bu, William C Mobley, Dongxian Zhang, Fred H Gage, Barbara Ranscht, Yun-wu Zhang,Stuart A Lipton, Wanjin Hong & Huaxi Xu (2013). Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome. Nature Medicine (2013) doi:10.1038/nm.311

Kai Zhang, Rotem Kenan, Yasuko Osakada, Wei Xu , Rachel S Sinit, Liang Chen, Xiaobei Zhao, Jia-Yun Chen, Bianxiao Cui and Chengbiao Wu (2013) Defective Axonal Transport of Rab7 GTPase Results in Dysregulated Trophic Signaling.  Journal of Neuroscience
2012
Weissmiller AM, Wu C. 2012, Current advances in using neurotrophic factors to treat neurodegenerative disorders. Transl Neurodegener. 2012 Jul 26;1(1):14. doi: 10.1186/2047-9158-1-14. PMID: 23210531 [PubMed] (Review)
 
Fjorback AW, Seaman M, Gustafsen C, Mehmedbasic A, Gokool S, Wu C, Militz D, Schmidt V, Madsen P, Nyengaard JR, Willnow TE, Christensen EI, Mobley WB, Nykjær A, Andersen OM. (2012) Retromer Binds the FANSHY Sorting Motif in SorLA to Regulate Amyloid Precursor Protein Sorting and Processing. J Neurosci. 2012 Jan 25;32(4):1467-1480.
 
X-Q Chen, Wang B, Wu C, Pan J, Yuan B, Su Y-Y, Jiang X-Y, Zhang X and Bao L(2011). Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary sensory neurons. Cell Research.
 
Chen L, Hoi-Ying N. Holman, Zhao Hao, Hans A. Bechtel, Michael C. Martin, Chengbiao Wu, Steven Chu Synchrotron infrared measurements of protein phosphorylation in living single PC12 cells during neuronal differentiation. Analytical Chemistry, 84(9), 4118-4125 (April 2012). 1.4.3, BSISB
 
AM Kleschevnikov, PV Belichenko, A Salehi and C Wu (2012). Chapter 10: Discoveries in Down syndrome: moving basic science to clinical care. In Progress in Brain Research, Vol 197. Editors M. Dierssen and R. de la Torre ISSN#0079-6123. Copyright Elsevier B.V. (Book Chapter)
2011
Sung K, Maloney MT, Yang J, Wu C. A novel method for producing mono-biotinylated, biologically active neurotrophic factors: an essential reagent for single molecule study of axonal transport. J Neurosci Methods. 2011 Sep 15;200(2):121-8. Epub 2011 Jul 2. PubMed PMID: 21756937; PubMed Central PMCID: PMC3158612.
2009
Wu C, Cui B, He L, Chen L, Mobley WC. The coming of age of axonal neurotrophin signaling endosomes. J Proteomics. 2009 Feb 15;72(1):46-55. Epub 2008 Nov 6. Review. PubMed PMID: 19028611; PubMed Central PMCID: PMC2677075.
2009
Belichenko PV, Kleschevnikov AM, Masliah E, Wu C, Takimoto-Kimura R, Salehi A, Mobley WC. Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome. J Comp Neurol. 2009 Feb 1;512(4):453-66. PubMed PMID: 19034952.
2008
Wan J, Cheung AY, Fu WY, Wu C, Zhang M, Mobley WC, Cheung ZH, Ip NY. Endophilin B1 as a novel regulator of nerve growth factor/ TrkA trafficking and neurite outgrowth. J Neurosci. 2008 Sep 3;28(36):9002-12. PubMed PMID: 18768694.
2007
Wu C, Ramirez A, Cui B, Ding J, Delcroix JD, Valletta JS, Liu JJ, Yang Y, Chu S, Mobley WC. A functional dynein-microtubule network is required for NGF signaling through the Rap1/MAPK pathway. Traffic. 2007 Nov;8(11):1503-20. Epub 2007 Sep 6. PubMed PMID: 17822405.

Cui B, Wu C, Chen L, Ramirez A, Bearer EL, Li WP, Mobley WC, Chu S. One at a time, live tracking of NGF axonal transport using quantum dots. Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13666-71. Epub 2007 Aug 14. PubMed PMID: 17698956; PubMed Central PMCID: PMC1959439.

Liu JJ, Ding J, Wu C, Bhagavatula P, Cui B, Chu S, Mobley WC, Yang Y. Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2223-8. Epub 2007 Feb 7. PubMed PMID: 17287360; PubMed Central PMCID: PMC1892971.