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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


As a postdoctoral fellow, 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 molecular mechanisms of motor neuron death with a focus on the role of superoxide dismutase (SOD1). Mutations in SOD1 have been linked to ALS and Dr. Zhao is interested in the pathology of various SOD1 mutations and how they affect interactions among motor neurons, microglia, astocytes, and T cells. A second focus is the role of immune-mediated injury in neuronal toxicity, and Dr. Zhao is investigating the potential of anti-inflammatory cytokines (interleukin-4 and interleukin 10) to reduce neuronal death.

Areas Of Expertise

ALS Lou Gehrig’s disease SOD1 Inflammation Cytotoxicity
Education & Training

, Baylor College of Medicine
, Beijing Medical University, Beijing

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:

The Promise of Novel Biomarker Approaches in Advancing Treatment Integrated Neuroscience Session
Zhao, W 2015, .

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:

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:

Novel therapeutic targets in neurodegenerative diseases: lessons from amyotrophic lateral sclerosis.
Appel, SH , Beers, DR, Henkel, JS & Zhao, W 2008, Current neurology and neuroscience reports, vol 8, no. 5, pp. 353-355. DOI:

Mutant SOD1G93A microglia are more neurotoxic relative to wild-type microglia
Xiao, Q, Zhao, W, Beers, DR, Yen, AA, Xie, W, Henkel, JS & Appel, SH 2007, Journal of Neurochemistry, vol 102, no. 6, pp. 2008-2019. DOI:

Effect of mild hypothermia treatment on cerebral metabolism in rats model of cerebral vasospasm after subarachnoid hemorrhage
Xu, X, Huang, HL, Zhi, DS, Zhao, WH, Mo, LD & Liang, WL 2007, Chinese Journal of Cerebrovascular Diseases, vol 4, no. 5.