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Weihua Zhao, MD, PhD

Assistant Research Professor of Neurology, Institute for Academic Medicine
Assistant Research Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Biography

During her postdoctoral training, Dr. Zhao conducted research on amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease. She investigated the roles of glutamate-mediated cytotoxicity, immune-mediated injury, and oxidative stress in motor neuron death. She also investigated the potential for a new phospholipid agent, VP025, to inhibit immune activation and protect motor neurons from injury. After completing her postdoctoral fellowship, Dr. Zhao joined the Methodist Hospital Research Institute as a scientist in the Department of Neurology.

Description of Research

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that attacks motor neurons in the brain and spinal cord. Dr. Zhao is interested in the underlying mechanisms of neuroinflammation on motor neuron death and relevant therapeutic targets. Current research efforts aim to understand the roles of microglia/monocytes and T-cells on immune-mediated injury and repair in ALS. Dr. Zhao is investigating the neuroprotective potential of regulatory immune cells as new therapeutic options for ALS. Gene mutations on SOD1, TDP-43, and C9ORF72 have been linked to ALS. Dr. Zhao is also interested in the pathology of various mutant proteins as well as abnormal peptides, and how they affect interactions among motor neurons, microglia, and T-cells in ALS.

Areas Of Expertise

ALS Lou Gehrig’s disease SOD1 Inflammation Cytotoxicity Immune Suppression Neuroprotection Neurocytotoxicity
Education & Training

Postdoctoral Fellowship , Baylor College of Medicine
MD , Beijing Medical University, Beijing
PhD , Peking University
Publications

Characterization of gene expression phenotype in amyotrophic lateral sclerosis monocytes
Zhao, W , Beers, DR, Hooten, KG, Sieglaff, DH, Zhang, A, Kalyana-Sundaram, S, Traini, CM, Halsey, WS, Hughes, AM, Sathe, GM, Livi, GP, Fan, GH & Appel, SH 2017, JAMA Neurology, vol 74, no. 6, pp. 677-685. DOI:

Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes
Zhao, W , Beers, DR, Hooten, KG, Sieglaff, DH, Zhang, A, Kalyana-Sundaram, S, Traini, CM, Halsey, WS, Hughes, AM, Sathe, GM, Livi, GP, Fan, GH & Appel, SH 2017, JAMA Neurology, vol 74, no. 6, pp. 677-685. DOI:

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity
Beers, DR , Zhao, W, Wang, J, Zhang, X, Wen, S, Neal, D, Thonhoff, JR, Alsuliman, AS, Shpall, EJ, Rezvani, K & Appel, SH 2017, JCI insight, vol 2, no. 5, pp. e89530. DOI:

TDP-43 activates microglia through NF-?B and NLRP3 inflammasome
Zhao, W , Beers, DR, Bell, S, Wang, J, Wen, S, Baloh, RH & Appel, SH 2015, Experimental Neurology, vol 273, pp. 24-35. DOI:

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis
Hooten, KG, Beers, DR, Zhao, W & Appel, SH 2015, Neurotherapeutics, vol 12, no. 2, pp. 364-375. DOI:

The Role of Regulatory T Cells and Microglia in Amyotrophic Lateral Sclerosis
Beers, DR , Zhao, W, Hooten, KG & Appel, SH 2015, . in S David (ed.), Neuroinflammation: New Insights into Beneficial and Detrimental Functions. John Wiley & Sons, Inc. pp. 235-249. DOI:

Role of Inflammation in Neurodegenerative Diseases
Appel, SH , Beers, DR & Zhao, W 2014, . in Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders. Elsevier, pp. 380-395. DOI:

Neuroimmunology of Amyotrophic Lateral Sclerosis
Henkel, JS, Beers, DR, Zhao, W & Appel, SH 2014, . in Neuroinflammation and CNS Disorders. Wiley-Blackwell, pp. 185-209. DOI:

Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis
Zhao, W , Beers, DR & Appel, SH 2013, Journal of Neuroimmune Pharmacology, vol 8, no. 4, pp. 888-899. DOI:

Erratum: Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival [EMBO Mol Med 5, 1] DOI: 10.1002/emmm.201201544
Henkel, JS, Beers, DR, Wen, S, Rivera, AL, Toennis, KM, Appel, JE, Zhao, W, Moore, DH, Powell, SZ & Appel, SH 2013, EMBO Molecular Medicine, vol 5, no. 2. DOI:

Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival
Henkel, JS, Beers, DR, Wen, S, Rivera, AL, Toennis, KM, Appel, JE, Zhao, W, Moore, DH, Powell, SZ & Appel, SH 2013, EMBO Molecular Medicine, vol 5, no. 1, pp. 64-79. DOI:

Regulatory T lymphocytes from ALS mice suppress microglia and effector T lymphocytes through different cytokine-mediated mechanisms
Zhao, W , Beers, DR, Liao, B, Henkel, JS & Appel, SH 2012, Neurobiology of Disease, vol 48, no. 3, pp. 418-428. DOI:

Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS
Liao, B, Zhao, W, Beers, DR, Henkel, JS & Appel, SH 2012, Experimental Neurology, vol 237, no. 1, pp. 147-152. DOI:

Reactive oxygen and nitrogen species - A driving force in amyotrophic lateral sclerosis
Henkel, JS, Beers, DR, Zhao, W & Appel, SH 2012, . in Systems Biology of Free Radicals and Antioxidants. Springer-Verlag Berlin Heidelberg, pp. 3141-3165. DOI:

Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice
Beers, DR , Zhao, W, Liao, B, Kano, O, Wang, J, Huang, A, Appel, SH & Henkel, JS 2011, Brain, Behavior, and Immunity, vol 25, no. 5, pp. 1025-1035. DOI:

The microglial-motoneuron dialogue in ALS
Appel, SH , Zhao, W , Beers, DR & Henkel, JS 2011, Acta Myologica, vol 30, no. JUNE, pp. 4-8.

Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis
Beers, DR, Henkel, JS, Zhao, W, Wang, J, Huang, A, Wen, S, Liao, B & Appel, SH 2011, Brain, vol 134, no. 5, pp. 1293-1314. DOI:

Extracellular mutant SOD1 induces microglial-mediated motoneuron injury
Zhao, W , Beers, DR, Henkel, JS, Zhang, W, Urushitani, M, Julien, JP & Appel, SH 2010, GLIA, vol 58, no. 2, pp. 231-243. DOI:

Microglia in ALS: The good, the bad, and the resting
Henkel, JS, Beers, DR, Zhao, W & Appel, SH 2009, Journal of Neuroimmune Pharmacology, vol 4, no. 4, pp. 389-398. DOI:

CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS
Beers, DR, Henkel, JS, Zhao, W, Wang, J & Appel, SH 2008, Proceedings of the National Academy of Sciences of the United States of America, vol 105, no. 40, pp. 15558-15563. DOI: