Email

huiz@bcm.edu

Positions

Director/Professor

Huffington Center on Aging
Baylor College of Medicine
Houston, TX US

Professor

Molecular and Human Genetics
Baylor College of Medicine

Professor

Molecular and Cellular Biology
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)

Zenith Award

Alzheimer’s Association (01/2004 - 01/2006)

Neuroscience of Aging (NIA-N) Review Committee

Member

NIH/NIA (01/2003 - 01/2007)

New Scholars Award

Ellison Medical Foundation (01/2000 - 01/2004)

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

• 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 July 28; 6 (9): 1142-60. Pubmed PMID: 25069841
• 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 January 7; 85 : 101-15. Pubmed PMID: 25533482
• 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..

Funding

Knockin Mouse Models of Alzheimer's Disease - #R01 AG020670

(04/01/2002 - 03/31/2022) 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 - 06/30/2020) 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.

Decoding the role of diverse astrocyte populations in aging and AD - #RF1 AG054111

(08/01/2016 - 06/30/2021) Grant funding from NIH

The major goals of the projects are to decipher the changes of molecular signatures of astrocyte populations as a function of aging and AD pathology and to determine the role of synaptogenic astrocytes in AD.

Convergence of tauopathy and Huntington’s disease through selective autophagy - #R01 AG057509

(09/01/2017 - 05/31/2022) Grant funding from NIH

The major goals of the project are to determine the mechanisms and functional role of HTT-mediated selective autophagy in Tau degradation and to test the polyQ dependency using Drosophila, cell and mouse models.