Positions
- Director/Professor
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Huffington Center on Aging
Baylor College of Medicine
Houston, TX US
- Professor
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Molecular and Human Genetics
Baylor College of Medicine
- Professor
-
Neuroscience
Baylor College of Medicine
- Huffington Foundation Endowed Chair in Aging
-
Baylor College of Medicine
Houston, Texas United States
Education
- BS from Peking University
- 01/1984 - Beijing, China
- PhD from Baylor College Of Medicine
- 01/1990 - Houston, Texas United States
- Postdoctoral Fellowship at Baylor College Of Medicine
- 11/1991 - Houston, TX United States
Honors & Awards
- Chair, NIA-N Review Committee
- NIH/NIA (01/2007 - 01/2008)
- New Scholars Award
- Ellison Medical Foundation (01/2000 - 01/2004)
- Zenith Award
- Alzheimer’s Association (01/2004 - 01/2006)
- Neuroscience of Aging (NIA-N) Review Committee
- Member
- NIH/NIA (01/2003 - 01/2007)
Professional Interests
- Autophagy-lysosomal pathway and neuron-immune interaction in Alzheimer's disease
Professional Statement
My laboratory has a long-standing interest in basic and translational research on Alzheimer’s disease (AD). Our expertise is mouse genetics and we are known for using sophisticated mouse models and innovative approaches to probe the biology and pathophysiology of AD. Our earlier investigation provided critical insights into the role of the amyloid precursor protein and presenilins in synaptic regulation and amyloid processing. Our recent effort has expanded from neurons to glial cells and from amyloid pathology to tau and neurofibrillary tangles. Our overarching hypotheses are AD is caused by faulty clearance of misfolded proteins and manifested by uncontrolled neuroinflammation. Accordingly, our major projects are focused on the investigation of the autophagy-lysosomal pathway and neuron-immune interaction with the goal to understand the disease mechanisms and to identify new therapeutic targets. Along these lines, we identified a highly selective and potent role of TFEB in the clearance of neurofibrillary tangles and deciphered cell-autonomous and non-cell-autonomous mechanisms in this process. Additionally, we mapped out a complement C3 and C3aR signaling axis that governs network function and innate immunity in the context of aging, AD and tauopathy. Lastly, we revealed a novel epoxy lipid metabolic pathway that becomes dysregulated in AD and show that targeting this pathway by small molecule inhibitors lead to potent anti-inflammatory and neuroprotective effects, supporting the potential of these inhibitors as AD therapy.Websites
Selected Publications
- Lian H, Yang L, Cole A, Sun L, Chiang AC, Fowler SW, Shim DJ, Rodriguez-Rivera J, Taglialatela G, Jankowsky JL, Lu HC, Zheng H "NFkB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease." Neuron. 2015 Jan 7;85:101-15. Pubmed PMID: 25533482
- Polito VA, Li H, Martini-Stoica H, Wang B, Yang L, Xu Y, Swartzlander DB, Palmieri M, di Ronza A, Lee VM, Sardiello M, Ballabio A, Zheng H "Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB." EMBO Mol Med. 2014 Jul 28;6(9):1142-60. Pubmed PMID: 25069841
- Litvinchuk A, Wan YW, Swartzlander DB, Chen F, Cole A, Propson NE, Wang Q, Zhang B, Liu Z, Zheng H "Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer's Disease.." Neuron. 2018;100:1337-1353.e5.31..
- Swartzlander, D.B., Propson, N.E., Roy, E.R., Saito, T., Saido, T., Wang, B., and Zheng, H. "Concurrent cell type-specific isolation and profiling of mouse brains in inflammation and Alzheimer’s disease.." 2018;3(13):e121109.
- Propson, N.E., Roy, E.R., Litvinchuk, A., Kohl, J., and Zheng, H. "Endothelial C3a receptor mediates vascular inflammation and BBB permeability during aging." J. Clin. Invest.. 2021;131:e140966. Pubmed PMID: 32990682
- Martini-Stoica, H., Cole, A.L., Swartzlander, D.B., Chen, F., Wan, Y.-W., Bajaj, L., Bader, D.A., Lee, V.M.Y., Trojankowski, J.Q., Liu, Z., Sardiello, M., and Zheng, H. "TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading.." J. Exp. Med.. 2018;215(9):2355-77.
- Martini-Stoica, H., Xu, Y., Ballabio, A., and Zheng, H. "The autophagy-lysosomal pathway in neurodegeneration: A TFEB perspective.." Trends Neurosci.. 2016;39(4):221-34.
- Xu, Y., Du, S., Marsh, J.A., Horie, K., Sato, C., Ballabio, A., Karch, C.M., Holtzman, D.M., and Zheng, H. "TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading." Mol. Psych.. 2020; Pubmed PMID: 32366951
- Du S, Jin F, Maneix L, Gedam M, Xu Y, Catic A, Wang MC, Zheng H "FoxO3 deficiency in cortical astrocytes leads to impaired lipid metabolism and aggravated amyloid pathology.." Aging Cell. 2021;20:e13432.
- Xu Y, Propson NE, Du S, Xiong W, Zheng H "Autophagy deficiency modulates microglial lipid homeostasis and aggravates tau pathology and spreading.." Proc Natl Acad Sci U S A.. 2021;118:e2023418118.
- Ghosh A, Comerota MM, Wan D, Chen F, Propson NE, Hwang SH, Hammock BD, Zheng H "An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer’s disease.." Sci Transl Med. 2020;12:eabb1206.
- d. Wang, B., Martini-Stoica, H., Qi, C., Lu, T.-C., Wang, S., Xiong, W., Qi, Y., Sardiello, M., Li, H., and Zheng, H. "TFEB-vacuolar ATPase signaling regulates lysosomal function and microglia activation in tauopathy." Nat. Neurosci.. 2024;27:48-62.
- d. Gedam, M., Comerota, M.M., Propson, N.E., Chen, T., Jin, F., Wang, M.C., and Zheng, H. "Complement C3aR depletion reverses HIF-1α-induced metabolic impairment and enhances microglial response to Aβ pathology." J. Clin. Invest.. 2023;133(12):e167501.
Funding
- Knockin Mouse Models of Alzheimer's Disease - #RF1 AG020670 (04/01/2002 - 03/31/2025) Grant funding from NIH
- The major goal of this project is to understand the pathogenic mechanisms of AD using novel and physiologically-relevant mouse models.
- Role of TFEB in Tauopathy - #R01 NS093652 (07/01/2015 - 06/30/2026) Grant funding from NIH
- The major goals of the projects are to investigate the role of neuronal vs. astrocytic TFEB in tau clearance and cell-to-cell transfer of neurofibrillary tangle pathology.
- Interrogating the interferon pathway in aging and AD - #RF1 AG057587 (06/01/2018 - 08/31/2023) Grant funding from NIH
- The major goals of the project are to delineate the cell-type specific mechanisms of type I interferon-mediated pathways and their functional contribution to aging and AD using innovative mouse models.
- Targeting a lipid-mediated pro-longevity pathway as Alzheimer’s therapy - #RF1 AG062257 (09/15/2018 - 08/31/2023) Grant funding from NIH
- The major goals of the project are to determine the role of a naturally occurring pro-longevity lipid molecule oleoylethanolamide (OEA) in AD-associated pathology and develop potent OEA analogs as therapeutic agent.
- Developing novel soluble epoxide hydrolase inhibitors for the treatment of AD - #U01 AG068031 (09/01/2020 - 05/31/2025) Grant funding from NIH/NIA
- The major goals of the project are to develop specific and CNS penetrating sEH inhibitors and testing the selected compounds in AD mouse models.
- Lysosome regulation and signaling in aging and AD - #P01 AG066606 (06/01/2021 - 02/28/2026) Grant funding from NIH/NIA
- : The major goals of the Program Project Grant are to understand how aging and tauopathy influence lysosomal properties, how these are communicated to the nucleus to engage distinct transcriptional programs, and how to harness the innate lysosomal signaling mechanisms to combat age-associated functional decline and delay neurodegenerative diseases. This proposal includes three cores and three research projects.
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