424 Life Sciences Center II
Brain cells consume copious amount of energy substrates for various functions. To coordinate substrate input and energy demand, cell organelles are required for orchestrating the evolutionarily conserved metabolic pathways. The intricate interactions between different organelles are pivotal in regulating metabolite trafficking, cell growth, metabolism, immune response, intercellular signaling, etc. Misrouted inter-organellar signaling leads to disrupted bioenergetic processes, and impairs the functions of energy demanding system such as the central nervous system. Indeed, perturbations to dysfunctional mitochondria and/or endolysosomes, two organelles fundamental to cell metabolism, often result in neurological disorders.
Deciphering the molecular underpinning of cell metabolism and bioenergetics will have huge impact on how we approach human diseases pertinent to immune and nervous systems. In our lab, we undertake a multi-disciplinary approach that integrates bioinformatics, model organism genetics, cell biology, lipidomics, and quantitative microscopy to study the cell biology of endolysosomes in brain and immune cells. We use the genetically tractable organism, Drosophila, to model organellar functions and map out the intricacy of the cellular pathways. Due to the versatility, robustness, and convenience of the genetic tools available to Drosophila research, we can swiftly build mechanistic models for specific cellular processes, and test novel concepts on relevant mammalian cells and animal models.
One of the main focuses of our research is to study how endolysosomes participate in organellar signaling and bioenergetics. Endolysosomal functions are particularly paramount to the immune and nervous systems, where pronounced phenotypes are manifested in lysosomal storage and neurodegenerative disorders. Our goal is to decipher the mechanisms of how endolysosomes coordinate signaling modules in different cell types in the nervous system, and to understand the pathogenesis of related diseases at molecular level. Our long-term goal is to leverage the mechanistic findings to develop therapeutic concepts for treating degenerative diseases that involve endolysosomal dysfunction.
Our research programs involve studies of vesicular trafficking, glial cell bioenergetics, transcellular signaling, and neuro-immune interaction. We are currently pursuing the following:
1) Dissecting the roles of endolysosomes in neuroglial lipid transport and lipid metabolism in neurodegenerative disorders such as Alzheimer’s.
2) Deciphering how vesicular transport and endolysosomal signaling regulate metabolic and bioenergetic processes in glial cells.
3) Studying how endolysosomes modulate signaling pathways in macrophage in response to microbes and damaged tissues.
4) Mechanism and functional outcome of the interplay between immune and nervous systems in the context of neurodegeneration.
26:120:524:01 Cell, Molecular, and Developmental Biology
26:120:526:01 Topics in Cell Biology: Biochemistry of Eukaryotes
B.Sc. in Biochemistry, Chinese University of Hong Kong, Hong Kong, 2005
Ph.D. in Physiology, Chinese University of Hong Kong, Hong Kong, 2009
Click this link for my up-to-date publications: https://www.ncbi.nlm.nih.gov/myncbi/ching%20on.wong.1/bibliography/public/
Wong CO*, Karagas NE*, Jung J, Wang Q, Rousseau MA, Chao Y, Insolera R, Soppina P, Collins CA, Zhou Y, Hancock JF, Zhu MX, Venkatachalam K. Regulation of longevity by depolarization-induced activation of PLC-β-IP3R signaling in neurons. Proc Natl Acad Sci U S A. 2021 Apr 20;118(16). doi: 10.1073/pnas.2004253118. (* co-first-author)
Martelli F, Zhongyuan Z, Wang J, Wong CO, Karagas NE, Roessner U, Rupasinghe T, Venkatachalam K, Perry T, Bellen HJ, Batterham P. Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila. Proc Natl Acad Sci U S A. 2020 Oct 13;117(41):25840-25850. doi: 10.1073/pnas.2011828117.
Wong CO. (2020) Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes. Int J Mol Sci. 2020 Jul 21;21(14). doi: 10.3390/ijms21145149.
Wong CO, Venkatachalam K. (2019) Motor neurons from ALS patients with mutations in C9ORF72 and SOD1 exhibit distinct transcriptional landscapes. Hum Mol Genet. 2019 Aug 15;28(16):2799-2810.
Jung J, Cho KJ, Naji AK, Clemons KN, Wong CO, Villanueva M, Gregory S, Karagas NE, Tan L, Liang H, Rousseau MA, Tomasevich KM, Sikora AG, Levental I, van der Hoeven D, Zhou Y, Hancock JF, Venkatachalam K. (2019) HRAS-driven cancer cells are vulnerable to TRPML1 inhibition. EMBO Rep. 2019 Apr;20(4). doi: 10.15252/embr.201846685.
Wong CO*, Gregory S, Hu H, Chao Y, Sepúlveda VE, He Y, Li-Kroeger D, Goldman WE, Bellen HJ, Venkatachalam K. (2017) Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages. Cell Host & Microbe 21(6):719-730. (cover article) * corresponding author
- Highlighted in: 1) Monahan AJ and Silverman N (2017) Relish the Thought and Channel Your Chloride, for Bacterial Clearance Depends on It. Cell Host & Microbe 21(6):657-659. 2) VanHook AM (2017) Macrophages don't take more than they can eat. Science Signaling 10(484). 3) Recommended by F1000Prime Faculty Dr. Dominique Ferrandon.
Lau OC*, Shen B*, Wong CO*, Tjong YW, Lo CY, Wang HC, Huang Y, Yung WH, Chen YC, Fung ML, Rudd JA, Yao X. (2016) TRPC5 Channels Participate in Pressure-sensing in Aortic Baroreceptor. Nature Communications. 7:11947 * co-first-author
Wong CO, Palmieri M, Akhmedov D, Li J, Chao Y, Broadhead GT, Zhu MX, Collins C, Berdeaux R, Sardiello M, Venkatachalam K. (2015) Diminished MTORC1-Dependent JNK-Activation Underlies the Neurodevelopmental Defects Associated with Lysosomal Dysfunction. Cell Reports. 12(12):2009-2020.
Zhou Y, Wong CO, Cho KJ, van der Hoeven D, Liang H, Thakur DP, Luo J, Babic M, Zinsmaier KE, Zhu, MX, Hu H, Venkatachalam K, Hancock JF. (2015) SIGNAL TRANSDUCTION. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling. Science. 349(6250):873-6.
Shen B*, Wong CO*#, Lau OC, Woo T, Bai S, Huang Y, Yao X#. (2015) Plasma Membrane Mechanical Stress Activates TRPC5 Channels. PLOS ONE. 10(4): e0122227. * co-first-author, # co-corresponding author
Wong CO, Chen K, Lin YQ, Chao Y, Duraine L, Lu Z, Yoon WH, Sullivan JM, Broadhead GT, Sumner CJ, Lloyd TE, Macleod GT, Bellen HJ, Venkatachalam K. (2014) A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission. Neuron. 84(4): 764-777. (cover article)
- Comment in: Imler E and Zinsmaier KE (2014) TRPV1 Channels: Not So Inactive on the ER. Neuron 84, 659-661.
Venkatachalam K, Wong CO, Zhu MX. (2014) The Role of TRPMLs in Endolysosomal Trafficking and Function. Cell Calcium. 58(1):48-56.
Feng X, Huang Y, Lu Y, Xiong J, Wong CO, Yang P, Xia J, Chen D, Du G, Venkatachalam K, Xia X, Zhu MX. (2014) Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane. J Biol Chem. 289(7):4262-72.
Venkatachalam K, Wong CO, Montell C. (2013) Feast or famine: role of TRPML in preventing cellular amino acid starvation. Autophagy. 9(1):98-100. (cover article)
Wong CO, Li R, Montell C, Venkatachalam K. (2012) Drosophila TRPML is required for TORC1 activation. Curr Biol. 22(17):1616-21.
Chan KH, Li T, Wong CO, Wong KB. (2012) Structural basis for GTP-dependent dimerization of hydrogenase maturation factor HypB. PLoS One. 7(1):e30547.
Wong CO*, Yao X. (2011) TRP channels in vascular endothelial cells. Adv Exp Med Biol. 704:759-80. * Corresponding author
Ma X, Cheng KT, Wong CO, O'Neil RG, Birnbaumer L, Ambudkar IS, Yao X. (2011) Heteromeric TRPV4-C1 channels contribute to store-operated Ca2+ entry in vascular endothelial cells. Cell Calcium. 50(6):502-9.
Shen B, Kwan HY, Ma X, Wong CO, Du J, Huang Y, Yao X. (2011) cAMP activates TRPC6 channels via the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)-mitogen-activated protein kinase kinase (MEK)-ERK1/2 signaling pathway. J Biol Chem. 286(22):19439-45.
Wong CO*, Sukumar P*, Beech DJ, Yao X. (2010) Nitric oxide lacks direct effect on TRPC5 channels but suppresses endogenous TRPC5-containing channels in endothelial cells. Pflugers Arch. 460(1):121-30. * co-first-author
Wong CO, Huang Y, Yao X. (2010) Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinases. Br J Pharmacol. 159(7):1486-96.
Ma X, Qiu S, Luo J, Ma Y, Ngai CY, Shen B, Wong CO, Huang Y, Yao X. (2010) Functional role of vanilloid transient receptor potential 4-canonical transient receptor potential 1 complex in flow-induced Ca2+ influx. Arterioscler Thromb Vasc Biol. 30(4):851-8.
Chan CM, Tsoi H, Chan WM, Zhai S, Wong CO, Yao X, Chan WY, Tsui SK, Chan HY. (2009) The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function. Int J Biochem Cell Biol. 41(11):2232-9.
Kwan HY, Wong CO, Chen ZY, Dominic Chan TW, Huang Y, Yao X. (2009) Stimulation of histamine H2 receptors activates TRPC3 channels through both phospholipase C and phospholipase D. Eur J Pharmacol. 602(2-3):181-7.
Wong CO*, Yao X. (2008) Cyclic nucleotide-gated channels: a familiar channel family with a new function? Future Cardiol. 4(5):505-15. * Corresponding author
Shen B, Cheng KT, Leung YK, Kwok YC, Kwan HY, Wong CO, Chen ZY, Huang Y, Yao X. (2008) Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels. J Mol Cell Cardiol. 45(3):437-45.
Cheng KT, Leung YK, Shen B, Kwok YC, Wong CO, Kwan HY, Man YB, Ma X, Huang Y, Yao X. (2008) CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 28(5):913-8.