Hui Zheng, Ph.D.

Professor

(713) 798-5804

Email

huiz@bcm.edu

Positions

Professor: Molecular and Human Genetics
Baylor College of Medicine

Professor: Neuroscience
Baylor College of Medicine

Education

Postdoctoral Fellowship at Baylor College Of Medicine: 11/1991 - Houston, TX, United States

PhD from Baylor College Of Medicine: 01/1990 - Houston, Texas, United States

BS from Peking University: 01/1984 - Beijing, China

Honors & Awards

New Scholars Award: Ellison Medical Foundation (01/2000 - 01/2004)

Zenith Award: Alzheimer’s Association (01/2004 - 01/2006)

Chair, NIA-N Review Committee: NIH/NIA (01/2007 - 01/2008)

CMND Study Section: Standing member.; NIH (07/2010 - 06/2016)

Medical & Scientific Advisory Council: Member.; Alzheimer Association (03/2011 - 06/2018)

Scientific Advisory Committee: Member (2008-2017); Co-Chair (2017-present).; BrightFocus Foundation (02/2008)

Scientific Advisory Board: Member.; Tau Consortium (06/2018)

Neuroscience of Aging (NIA-N) Review Committee: Member; NIH/NIA (01/2003 - 01/2007)

Scientific Advisory Committee: Member (2008-2017), Co-Chair (2017-present); BrightFocus Foundation (02/2008)

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

Zheng Lab Site

VIICTR Publications List

Selected Publications

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.
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.
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.
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., Zhang, S., and Zheng, H.. " The cargo receptor SQSTM1 ameliorates neurofibrillary tangle pathology and spreading through selective targeting of pathological microtubule associated protein Tau.. " Autophagy. 2018 ; 5 : 1-16.
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..
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.
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.
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.
Ghosh A, Comerota MM, Wan D, Chen F, Propson NE, Hwang SH, Hammock BD, Zheng H. " n epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer’s disease.. " Sci Transl Med.. 2020 ; 12 : eabb1206.
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.

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.