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Personal profile
Personal profile
Dr. Appel is former chair of the Stanley H. Appel Department of Neurology, Professor of Neurology at Weill Cornell Medical College, and the Peggy and Gary Edwards Distinguished Chair for the Treatment and Research of ALS at the Houston Methodist Research Institute. He was previously Chair of the Department of Neurology at Baylor College of Medicine as well as Chief of the Neurology division and the James B. Duke Professor of Medicine at Duke University Medical Center, North Carolina.
Dr. Appel is a native of Massachusetts and received his Bachelor Degree at Harvard University and his Medical Degree from Columbia College of Physicians and Surgeons. He is Director of the MDA/ALSA ALS Research and Clinical Center at Houston Methodist Neurological Institute, and past Director of a National Institute of Aging Alzheimer’s Disease Research Center.
Dr. Appel is a member of numerous professional societies and committees, and is the author of 15 published books and over 350 articles on topics such as ALS, neuromuscular disease, Alzheimer’s Disease, and Parkinson’s Disease. He has received a number of awards for his accomplishments in Neurology and Biochemistry, including the Gold Medal Award in 1997 from Columbia College of Physicians and Surgeons for “Distinguished Achievements in Medicine”, the Sheila Essey Award in 2003 from the American Academy of Neurology for “outstanding research in Amyotrophic Lateral Sclerosis”, Elected Fellow of the American Association for the Advancement of Science in recognition of the “dedication and commitment to advancing science and serving society” in 2003, Baylor College of Medicine Alumni Association Distinguished Faculty Award in 2004, MDA’s Wings Over Wall Street Diamond Award in 2004, Texas Neurological Society Lifetime Achievement Award in 2005 and the Forbes Norris Award for “compassion and love for humanity in research and treatment in patients with ALS” from the International Alliance of ALS/MND Associations in 2005, and the Museum District Business Alliance Award in recognition of his commitment to research, patient care, and education, 2007, and the recipient of the Houston Academy of Medicine 2008 John P. McGovern Compleat Physician Award. He is also named 2008 Best of the Best Physicians by the Medical Journal Houston.
Research interests
Research in Dr. Appel’s laboratory focuses on developing new insights into neurodegenerative diseases, with a primary emphasis on amyotrophic lateral sclerosis (ALS). The major goal is to develop therapeutics that suppress neuroinflammation and the immune/inflammatory alterations that drive neurodegenerative disease progression. In the mSOD1 mouse model of ALS, activated microglia, and T-cell lymphocytes drive disease progression. In vitro studies documented that motor neuron cytotoxicity is produced by pro-inflammatory M1 microglia, and neuroprotection is mediated by anti-inflammatory M2 microglia. The motor neuron injury that initiates the process can be reproduced in vitro with misfolded proteins (mSOD, TDP-43, and FUS) which activate microglia and promote an M1 phenotype that kills motor neurons. Neuroprotective cytokines IL-4 and IL10 released from M2 microglia/macrophages enhance motor neuron survival. In vitro Tregs not only suppress proliferation of Th1, but also suppress pro-inflammatory M1 microglia. These studies suggest that during early stages of disease, motor neurons are capable of intracellular repair abetted by surrounding glia enhanced and modulated by Tregs. However, with increasing injury within the motor neuron, misfolded proteins or their surrogates are released as danger signals and promote the pro-inflammatory M1 phenotype, diminishing protective Tregs and enhancing pro-inflammatory Th1 and Th17.
Education/Academic qualification
Neurology, Residency, National Heart, Lung, and Blood Institute, National Institutes of Health
Jul 1 1965 → Jun 1 1966
Award Date: Jun 1 1966
Molecular Biology, Research Fellowship, Duke University Medical Center
Jan 1 1962 → Jan 1 1964
Award Date: Jan 1 1964
Neurology, Residency, Mount Sinai Medical Center
Jul 1 1961 → Jun 1 1962
Award Date: Jun 1 1962
Internal Medicine, Internship, Harvard University
Jul 1 1960 → Jun 1 1961
Award Date: Jun 1 1961
MD, Columbia University College of Physicians and Surgeons
… → May 31 1960
Award Date: May 31 1960
Research Area Keywords
- Neurosciences
- Regenerative Medicine
Free-text keywords
- Neurodegenerative diseases
- Amyotrophic Lateral Sclerosis
- Alzheimer’s disease
- Parkinson’s disease
- Neuromuscular disorders
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- 1 Similar Profiles
Collaborations and top research areas from the last five years
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A Phase I Clinical Trial, Using Interleukin-2 (IL-2) and Abatacept in Patients with Frontotemporal Disorders
Faridar, A. (PI), Appel, S. H. (Key Personnel), Masdeu, J. C. (Key Personnel) & Pascual, B. (Key Personnel)
6/10/24 → …
Project: Clinical Trial
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Regulatory T cells as a novel therapeutic target in Alzheimer's Disease
Appel, S. H. (PI), Faridar, A. (PI) & Masdeu, J. C. (PI)
8/1/21 → 6/30/25
Project: Non Profit
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HEALEY ALS Platform Trial - Regimen-Specific Appendix D - For pridopidine 45 mg oral capsule administered twice daily (BID) or its matching placebo.
Appel, S. H. (PI), Shroff, S. (PI), Greene, E. P. (CoI) & Liao, B. (CoI)
6/29/21 → 7/23/25
Project: Non Profit
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A Study of Biological Markers for the Nervous and Immune Systems and Free Radical Mediated Processes in Amyotrophic Lateral Sclerosis (ALS)
Appel, S. H. (PI), Beers, D. (Key Personnel), Greene, E. P. (Key Personnel), Lai, E. C. (Key Personnel), Liao, B. (Key Personnel), Shroff, S. (Key Personnel) & Zhao, W. (Key Personnel)
8/13/20 → …
Project: Clinical Trial
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HEALEY ALS Platform Trial - Regimen-Specific Appendix A - For 0.3mh/kg SC zilucoplan administered once daily and placebo
Appel, S. H. (PI), Shroff, S. (PI), Greene, E. P. (CoI) & Liao, B. (CoI)
7/24/20 → 7/23/25
Project: Non Profit
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A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis
Thonhoff, J. R., Beers, D. R., Zhao, W., Faridar, A., Thome, A., Wen, S., Zhang, A., Wang, J. & Appel, S. H., 2024, In: Frontiers in Neurology. 15, p. 1415106 1415106.Research output: Contribution to journal › Article › peer-review
Open Access -
Primary visual cortex pathology in ALS patients with C9ORF72 expansion
Cykowski, M. D., Arumanayagam, A. S., Powell, S. Z. & Appel, S. H., Sep 2024, In: Brain Pathology. 34, 5, e13229.Research output: Contribution to journal › Letter › peer-review
Open Access1 Scopus citations -
A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer’s disease
Faridar, A., Eid, A. M., Thome, A. D., Zhao, W., Beers, D. R., Pascual, M. B., Nakawah, M. O., Roman, G. C., Davis, C. S., Grundman, M., Masdeu, J. C. & Appel, S. H., Nov 16 2023, In: Translational Neurodegeneration. 12, 1, p. 54 54.Research output: Contribution to journal › Letter › peer-review
Open Access5 Scopus citations -
Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development
for the Healey ALS Platform Trial Study Group, HEALEY ALS Platform Trial Study Group, Biostatisticians, Investigators, Clinical Operations Team & Medical Monitors, Feb 1 2022, In: Annals of Neurology. 91, 2, p. 165-175 11 p.Research output: Contribution to journal › Article › peer-review
Open Access50 Scopus citations -
Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis
Thonhoff, J. R., Berry, J. D., Macklin, E. A., Beers, D. R., Mendoza, P. A., Zhao, W., Thome, A. D., Triolo, F., Moon, J. J., Paganoni, S., Cudkowicz, M. & Appel, S. H., Nov 29 2022, In: Neurology: Neuroimmunology and NeuroInflammation. 9, 6, e200019.Research output: Contribution to journal › Article › peer-review
Open Access21 Scopus citations