Hui Zheng Lab Publications

2020-present

Peña-Ramos, O.*, Gedam, M.*, Zhang, X., Wang, S., Qi, C., Huang, T.-H., Rajpurohit, C.S., Dunlap, M., Deng, Y., Auld, N., Jung, S.Y., Li, H., Luo, L., Peng, J., Cheng, C., and Zheng, H. Astrocyte cell-surface proteomics identified CD44 as an OPN/SPP1 receptor regulating lipid metabolism and glial crosstalk in Alzheimer’s disease. bioRxiv 2025.12.05.692670; doi: https://doi.org/10.64898/2025.12.05.692670
Zheng, H. (2026). Diverse functions of lysosomes in brain health and Alzheimer’s disease. In “Pathobiology of Alzheimer’s disease”. S.S. Sisodia and R. Tanzi ed. Springer Nature Press.
Xiong, Y., Sharma, J., Young, M., Xiong, W., Jazayeri, A., Poncha, K., Ilagan, M.X., Wang, Q., Zheng, H., Young, N., Gao, B., and Sardiello, M. (2026). TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade. Nat. Comm., in press.
Perez, G., Lai, Z., Edwards, G.A.III, Dundee, J., Qi, C., Qi, Y., Park, Y.-J., Lu, T.-C., Uddin, D.M., Zhao, R., Zheng, H., Li, H., and Jankowsky, J.L. (2026). Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models. Mol. Neurodegen., 21(1):2.
Hu, B., Shi, Y., Chen, Y.-T., Drolet, N., Xiong, F., Zhu, X., Carillo, E., Jayaraman, V., Lee, D.-F., Soto, C., Zhong, S., Xu, X., Wen, X., Rajpurohit, C., Zheng, H., and Li, W. (2025). Rewired m6A methylation of promoter antisense RNAs in Alzheimer’s disease regulates global gene transcription in the 3D nucleome. Nat. Comm., 16: 5251.
Park, Y., Lu, T.-C.,Jackson, T., Goodman, L. D., Ran, L., Chen, J., Liang, C.Y., Harrison, E., Ko, C., Chen, X., Wang, B., Hsu, A.-L., Ochoa, E., Bieniek, K. F., Yamamoto, S., Zhu, Y., Zheng, H., Qi, Y., Bellen, H., and Li, H. (2025). Distinct systemic impacts of Aβ42 and Tau revealed by whole-organism snRNA-seq in Drosophila. Neuron, 113(13): 2065-2082.
Deng, D., Guan, Y., Mutlu, A.S., Wang, B., Guo, S.M., Zheng, H., and Wang, M.C. (2025). Quantitative profiling pH heterogeneity of acidic endolysosomal compartments using fluorescence lifetime imaging microscopy. Mol. Biol. Cell, 36(3)br8, 1-11.
Wang, S., Qi, C., Rajpurohit, C., Ghosh, B., Xiong, W., Wang, B., Qi, Y., Hwang, S. H., Hammock, B. D., Li, H., Gan, L., and Zheng, H. (2025). Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model. Mol. Neurodegen., (2025) 20:44.
Gedam, M., and Zheng, H. (2024). Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease. Eur. J. Immunol. 2023;0:2350815. DOI: 10.1002/eji.2350815.
Wang, B., Martini-Stoica, H., Qi, C., Lu, T.C., Wang, S., Xiong, W., Qi, Y., Xu, Y., Sardiello, M., Li, H. and Zheng, H., (2023). TFEB-vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy. Nat Neurosci 27, 48–62 (2024). https://doi.org/10.1038/s41593-023-01494-2.
Cemorata, M.M., Gadam, M., Xiong, W., Jin, F., Deng, L., Wang, M.C., Wang, J., Zheng, H. (2023). Oleoylethanolamide facilitates PPARα and TFEB signaling and attenuates Aβ pathology in a mouse model of Alzheimer’s disease. Mol. Neurodegen., (2023) 18:56. https://doi.org/10.1186/s13024-023-00648-x.
Gadam, M., Cemorata, M.M., Propson, N.E., Chen, T., Jin F., Wang, M.C., and Zheng, H. (2023). Complement C3aR depletion reverses HIF-1α-induced metabolic impairment and enhances microglial responses to Aβ pathology. J. Clin. Invest. 2023; 133(12):e167501.
Niu, M., Cao, W., Wang, Y., Zhu, Q., Luo, J., Wang, B., Zheng, H., Weitz, D.A., Zong, C. (2023). Droplet-based transcriptome profiling of individual synapses. Nat. Biotech., https://doi.org/10.1038/s41587-022-01635-1.
Roy, E.R., Chiu, G., Li, S., Propson, N.E., Kanchi, R., Wang, B., Coarfa, C., Zheng, H., and Cao, W. (2022). Concerted type 1 interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques. Immunity, 55, 879-894.
Du, S., Jin, F., Maneix, L., Gedem, M., Xu, Y., Catic, A., Wang, M.C., and Zheng, H. (2021). FoxO3 deficiency in cortical astrocytes leads to impaired lipid metabolism and aggravated amyloid pathology. Aging Cell, 20(8):e13432.
Xu, Y., Propson, N.E., Du, S., Xiong, W., and Zheng, H. (2021). Autophagy deficiency modulates microglial lipid homeostasis and aggravates tau pathology and spreading. Proc. Natl. Acad. Sci. USA, 118(27):e2023418118.
Chen, F., Swartzlander, D.B., Ghosh, A., Fryer, J.D., Wang, B., and Zheng, H. (2021). Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer’s disease neuropathology. Mol. Neurodegen., 16:5.
Propson, N.E., Roy, E.R., Litvinchuk, A., Kohl, J., and Zheng, H. (2021). Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging. J. Clin. Invest. 131(1):e140966.
Xu, Y., Du, S., Marsh, J.A., Horie, K., Sato, C., Ballabio, A., Karch, C.M., Holtzman, D.M., and Zheng, H. (2021). TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading. Mol. Psychiatry, 26(10): 5925-39.
Ghosh, A., Comerota, M.E., Wan, D., Chen, F., Propson, N.E., Hwang, S.H., Hammock, B.D., and Zheng, H. (2020). An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer’s disease. Sci. Transl. Med. 12, eabb1206.
Roy, E.R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N.E., Xu, Y., Jankowsky, J.L., Liu, Z., Lee, V., M.-Y., Trojankowski, J.Q., Ginsberg, S.D., Butovsky, O., Zheng, H.*, and Cao, W*. (2020). Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J. Clin. Invest. 130(4): 1912-30. *co-corresponding.

2010-2019

Wu, Y., Du, S., Johnson, J., Tung, H.-Y., Landers, C.T., Liu, Y., Seman, B.G., Wheeler, R.T., Costa-Mattioli, M., Kheradmand, F., Zheng, H., and Corry, D.B. (2019). Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits. Nat. Commun., 10:58.
Xu, Y., Zhang, S., and Zheng, H. (2019). The cargo receptor SQSTM1 ameliorates Tau pathology and spreading through selective targeting of pathological Tau. Autophagy, 15(4): 583-598.
Litvinchuk, A., Wan, Y.-W., Swartzlander, D., Chen, F., Propson, N., Cole, A., Wang, Q., Zhang, B., Liu, Z., and Zheng, H. (2018). Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer's disease. Neuron, 100(6): 1337-53.
Martini-Stoica, H., Cole, A., Swartzlander, D.B., Chen, F., Wan, Y.-W., Bajaj, L., Bader, D., Lee, V. M.Y., Trojankowski, J.Q., Liu, Z., Sardiello, M., and Zheng, H. (2018). TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading. J. Exp. Med., 215(9): 2355-77.
Swartzlander, D.B.*, Propson, N.E.*, Roy, E.R, Saito, T., Saido, T., Wang, B., and Zheng, H. (2018). Concurrent cell-type specific isolation and profiling of mouse brains in inflammation and Alzheimer’s disease. JCI Insight, 3(13):e121109. *Equal contribution.
Li, Y., Chen, Z., Gao, Y., Pan, G. Zheng, H., Zhang, Y., Xu, H., Bu, G., and Zheng, H. (2017). Synaptic adhesion molecule Pcdh-γC5 mediates synaptic dysfunction in Alzheimer's disease. J. Neurosci., 37(38): 9259-68.
Wang, B., Li, H., Mutlu, S.A., Bowser, D.A., Moore, M., Wang, M.C., and Zheng, H. (2017). The amyloid precursor protein is a conserved receptor for Slit to mediate axon guidance. eNeuro, 4(3) e0185-17.2017.
Xu, Y., Martini-Stoica, H. and Zheng, H. (2016). A seeding based cellular assay of tauopathy. Mol. Neurodegen. 11:32.
Lian, H.*, Litvinchuk, A.*, Chiang A., Aithmitti, N., Jankowsky, J.L. and Zheng, H. (2016). Astrocyte-microglia crosstalk through complement activation modulates amyloid pathology in mouse models of Alzheimer’s disease. J. Neurosci., 36(2): 577-89. *Equal contribution.
Justice, N.J., Huang, L., Tian, J.-B., Cole, A., Pruski, M., Hunt, A.J., Flores, R., Arenkiel, B.R. and Zheng, H. (2015). Post-traumatic stress disorder-like induction elevates A levels which directly activates CRF neurons to exacerbate stress responses. J. Neurosci., 35(6): 2612-23.
Lian, H., Yang, L., Cole, A., Sun, L., Chiang, A., Flower, S.W., Shim, D.J., Rodriguez-Rivera, J., Taglialatela, G., Jankowsky, J.L., Lu, H.-C. and Zheng, H. (2015). NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer’s disease. Neuron, 85(1): 101-115.
Wang, B., Wang, Z., Sun, L., Yang, L., Li, H., Cole, A., Rodriguez-Rivera, J., Lu, H.-C. and Zheng, H. (2014). The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons. J. Neurosci., 34(40): 13314-13325.
Li, H., Guo, Q., Inoue, T., Polito, V.A., Tabuchi, K., Hammer, R.E., Pautler, R.G., Taffet, G.E. and Zheng, H. (2014). Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow. Mol. Neurodegen., 9:28.
Polito, V.*, Li, H.*, Martini-Stoica, H.*, Wang, B.,Yang, L., Xu, Y., Swartzlander, D., Palmieri, M., di Ronza, R., Li, V. M.-Y., Sardiello, M. Ballabio, A., and Zheng, H. (2014). Selective clearance of aberrant Tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol. Med., 6(9): 1142-1160. *Equal contribution.
Guo, Q., Li, H., Cole, A.L., Hur, J.-Y., Li, Y. and Zheng, H. (2013). Modeling Alzheimer’s disease in mouse without mutant protein overexpression: Cooperative and independent effects of Abeta and Tau. PLoS ONE, 8(1): e80706.
Lian, H., Shim, D.J., Gaddam, S.S.K., Rodriguez-Rivera, J., Ritner, B.R., Pautler, R.G., Robertson, C.S. and Zheng, H. (2012). IkB deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: Implications for functional recovery. Mol. Neurodegen.7:47.
Wiese, M., Antebi, A., and Zheng, H. (2012). Regulation of neuronal APL-1 expression by cholesterol starvation. PLoS ONE, 7(2): e32038.
Guo, Q., Zheng, H.* and Justice, N.J.* (2012). Central Corticotropin Releasing Factor system perturbation promotes HPA axis hyperactivity and elevated anxiety-related behavior in a familial Alzheimer's Disease knock-in mouse model. Neurobiol Aging 33(11): 2678-2691. *co-corresponding.
Guo, Q., Li, H., Gaddam, S.S.K., Justice, N.J., Robertson, C.S., and Zheng, H. (2012). Amyloid precursor protein revisited: Neuronal-specific expression and the highly stable nature of soluble derivatives. J. Biol. Chem. 287(4): 2437-45.
Wang, B., Harrison, W., Overbeek, P. and Zheng, H. (2011). Transposon mutagenesis with coat color genotyping identifies an essential role of SKOR2 in Sonic Hedgehog signaling and cerebellum development. Development, 138: 4487-4497.
Shim, D.J., Yang, L., Reed, J.G., Nobels, J.L., Chiao, P.J., and Zheng, H. (2011). Disruption of the NF-κB/IκBα autoinhibitory loop improves cognitive performance and promotes hyperexcitability of hippocampal neurons. Mol. Neurodegen., 6:42.
Barbagallo, A.P.M., Wang, Z., Zheng, H., and D’Adamio, L. (2011). The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. PLoS ONE, 6: e18006.
Barbagallo, A.P.M., Wang, Z., Zheng, H., and D’Adamio, L. (2011). A single tyrosine residue in the amyloid precursor protein intracellular domain is essential for developmental function. J. Biol. Chem., 286: 8717-8721.
Li, H., Wang, B., Wang, Z., Guo, Q., Tabuchi, K., Hammer, R., Sudhof, T., and Zheng, H. (2010). Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP. Proc. Natl. Acad. Sci. USA, 107: 17362-17367.
Wiese, M., Antebi, A. and Zheng, H. (2010). Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans. PLoS ONE, 5: e12790.
Li, H., Wang, Z., Wang, B., Guo, Q., Dolios, G., Tabuchi, K., Hammer, R.E., Sudhof, T.C., Wang, R. and Zheng, H. (2010). Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J. Biol. Chem., 285: 30598-30605.
Peethumnongsin, E., Yang, L., Kallhoff-Munoz, V., Hu, L., Takashima, A., Pautler, R.G., and Zheng, H. (2010). Convergence of presenilin- and tau-mediated pathways on axonal trafficking and neuronal function. J. Neurosci., 30: 13409-13418.

2000-2009

Yang, L., Wang, Z., Wang, B., Justice, N., and Zheng, H. (2009). Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J. Neurosci., 29: 15660-15668.
Shelton, C.C., Zhu, L., Chau, D., Yang, L., Wang, R., Djaballah, H., Zheng, H., and Li, Y.-M. (2009). Modulation of γ-secretase specificity using small molecule allosteric inhibitors. Proc. Natl. Acad. Sci. USA, 106: 20228-20233.
Wang, Z., Wang, B., Yang, L., Guo, Q., Aithmitti, N., Songyang, Z. and Zheng, H. (2009). Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J. Neurosci., 29:10788-10801. Selected as a “This Week in the Journal” article.
Kallhoff-Munoz, V., Hu, L., Chen, X. Pautler, R.G. and Zheng, H. (2008). Genetic dissection of γ-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death. J. Neurosci., 28:11421-11431.
Yang, L., Wang, B. Long, C., Wu, G. and Zheng, H. (2007). Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses. Neuroscience, 149: 768-778.
Wang, B., Yang, L., Wang, Z. and Zheng, H. (2007). Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc. Natl. Acad. Sci. USA, 104: 14140-14145.
Kallhoff, V., Peethumnongsin, E. and Zheng, H. (2007). Lack of α-synuclein increases amyloid plaque accumulation in a transgenic mouse model of Alzheimer’s disease. Mol. Neurodegeneration, 2:6.
Wang, R., Wang, B., He, W., and Zheng, H. (2006). Wild-type presenilin protects against Alzheimer’s disease mutation-induced amyloid pathology. J. Biol. Chem., 281: 15330-15336.
Deng, Y., Tarassishin, L., Kallhoff, V., Peethumnongsin, E., Wu, L., Li, Y. and Zheng, H. (2006). Deletion of presenilin 1 hydrophilic loop sequence leads to impaired -secretase activity and exacerbated amyloid pathology. J. Neurosci. 26: 3845-3854.
Wang, R., Tang, P., Wang, P., Boissy, R.E. and Zheng, H. (2006). Regulation of tyrosinase trafficking and processing by presenilins: Partial loss of function by familial Alzheimer’s disease mutation. Proc. Natl. Acad. Sci. USA 103: 353-358.
Wang, P., Yang, G., Mosier, D.R., Chang, P., Zaidi, T., Gong, Y.-D., Zhao, N.-M., Dominguez, B., Lee, K.-F., Gan, W.-B. and Zheng, H. (2005). Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2. J. Neurosci. 25: 1219-1225.
Wang, R., Dineley, K.T., Sweatt, J.D, and Zheng, H. (2004). Presenilin 1 Alzheimer’s disease mutation leads to impaired adult neurogenesis and defective associative learning. Neuroscience 126: 305-312.
Qyang, Y., Chambers, S.M., Wang, P., Xia, X., Chen, X., Goodell, M.A. and Zheng, H. (2004). Myeloproliferative disease in mice with reduced presenilin gene dosage: Effect of -secretase blockage. Biochemistry 43: 5352-5359.
Wang, P., Pereira, F. A., Beasley, D., and Zheng, H. (2003). Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development 130: 5019-5029.
Kang, D.E., Soriano, S., Xia, X., Eberhart, C.G., De Strooper, B., Zheng, H., and Koo, E.H. (2002). Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell 110: 751-762.
Xia, X., Wang, P., Sun, X., Soriano, S., Shum, W.-K., Trumbauer, M.E., Takashima, A., Koo, E.H., and Zheng, H. (2002). The aspartate-257 of presenilin 1 is indispensable for mouse development and production of -amyloid peptides through -catenin independent mechanisms. Proc. Natl. Acad. Sci. USA 99: 8760-8765.
Dineley, K.T., Xia, X., Bui, D., Sweatt, J.D., and Zheng, H. (2002). Accelerated plaque accumulation, associative learning deficits and up-regulation of 7 nicotinic acetylcholine receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J. Biol. Chem. 277: 22768-22780.
Xia, X., Qian, S., Soriano, S., Wu, Y., Fletcher, A., Wang, X.-J., Koo, E.H., Wu, X., and Zheng, H. (2001). Loss of presenilin 1 is associated with enhanced -catenin signaling and skin tumorigenesis. Proc. Natl. Acad. Sci. USA 98: 10863-10868.