IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis
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Article Information
- Received April 26, 2019
- Accepted in final form August 28, 2019
- First Published October 14, 2019.
Author Disclosures
- Marlena Wosiski-Kuhn, BA,
- Mac Robinson, PhD,
- Jane Strupe, BS,
- Phonepasong Arounleut, BS,
- Matthew Martin, MD,
- James Caress, MD,
- Michael Cartwright, MD,
- Robert Bowser, PhD,
- Merit Cudkowicz, MD,
- Carl Langefeld, PhD,
- Gregory A. Hawkins, PhD and
- Carol Milligan, PhD
- Marlena Wosiski-Kuhn, BA,
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- Mac Robinson, PhD,
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- Jane Strupe, BS,
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- Phonepasong Arounleut, BS,
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- Matthew Martin, MD,
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- James Caress, MD,
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Muscle & Nerve, Associate Editor, 2016-present
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Orion Pharmaceuticals Cytokinetics Incorporated
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- Michael Cartwright, MD,
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Elsevier, Inc, 2012-present  royalties from sale of textbook
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- Robert Bowser, PhD,
1)MT Pharma; 2) Above & Beyond, LLC.
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1)Scientific Reports, Editor, 2017 - present; 2) International Journal of Proteomics, Editor, 2010 - present; 3)American Journal of Neurodegenerative Disease, Senior Editorial Board, 2012-present
1)Biomarkers for the diagnosis and prognosis of ALS; 2) Biomarkers to monitor drug treatment of ALS and other neuromuscular disease patients; 3)Biomarkers for detecting and treating joint related pain.
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1)Iron Horse Diagnostics, Inc., President, 2012 - present.
1)Above & Beyond, LLC
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1)NIH NS091299
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1)ALS Association; 2)Target ALS; 3) Muscular Dystrophy Association
1)Iron Horse Diagnostics, Inc.
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- Merit Cudkowicz, MD,
Lilly DSMB
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Neurotherapeutics editorial board JAMA Neurology editorial board
Metabolomics in ALS - patent MIR 155 inhibitor - patent
UptoDate MND chapter
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Cytokinetics, Biogen, Orion, ImmunityPharm, Biohaven, Avexis, Revalesio, MT Pharma
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NINDS - U01 NeuroNEXT
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Muscular dystrophy association, als association, als finding a cure foundation, ALS One
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- Carl Langefeld, PhD,
(1) Oklahoma Medical Research Foundation, Wake Forest Nonhuman Primate Center (2) National Jewish Health
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(2) NIH; (2) National Jewish Health
Rheumatic Disease Clinics
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U01 NS069763-01 08/01/2010 - 07/31/2016 NINDS Minorities with Ischemic Stroke Study (ERICH) PI of Biostatistics and Bioinformatics Center P01 AR048929 09/01/2011 Â 08/30/2016 NIH Gene Expression in Pediatric Arthritis PI of Analysis Center Subcontract P30 CA12197 02/01/2012 Â 01/31/2017 NCI Comprehensive Cancer Center of Wake Forest University- Cancer Center Support Grant Co-Investigator HG007112 -01 05/01/2012 Â 03/31/2017 NIH Exome Sequencing to Identify CVD Risk Variants in Hispanic and African Americans Co-PI R01 DK090111-01 04/01/2011 - 03/31/2017 NIDDK Mapping Diabetes Susceptibility by expression traits in African Americans Co-Investigator R01 DK071891 07/01/2005 Â 06/30/2017 NIDDK Subclinical DVD in African American Type 2 Diabetes Co-Investigator R21 DK106554 08/01/2015 Â 07/31/2017 NIH Biomarkers for Molecular-Based-Decision-Making in Diagnosis and Treatment of Interstitial Cystitis Co-Investigator R01 HL 114587 06/01/2013 Â 05/31/2018 NIH Genetic Risk for Granulomatous Interstitial Lung Disease PI of Subcontract R01 HL119962 07/01/2013 Â 06/30/2018 NHLBI The Role of Hepatocyte ABCA1 in Lipid Metabolism and Transport Co-Investigator UG1 VA189824 08/01/2014 Â 07/31/2019 NCI Wake Forest NCORP Research Base Co-Investigator R01 NS093870 02/01/2016 Â 01/31/2021 NIH Recurrence of Stroke in Minority Populations Co-Investigator
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RILITE Foundation 12/01/2015 Â 11/30/2017 Informing Drug Repositioning and Development Through Genomics PI
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- Gregory A. Hawkins, PhD and
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Current Support NOT related to current publication: 1 R03 AI137866-01 (PI: Hawkins) 04-1-2018 to 03-31-20 National Institute of Health TDC: $100,000 Development of IL6 Trans-signaling Mouse Model as a Shared Resource This project is to develop a mouse model that lacks incorporates a single nucleotide coding change that is predicted to make the IL6 receptor more susceptible to shedding. The mouse should model human subjects who inherit the IL6R Ala allele. If successful the model will be used in research related to neurodegenerative diseases, asthma, cancer and cardiovascular diseases. AL170130 (Hawkins, PI) 07/15/18-06/30/20 Department of the Army DC: $250,000 Generation of a Mouse Model to Investigate IL-6 Trans-signaling in ALS In this study, we are proposing that IL6 transsignaling plays a role in making ALS progression and severity worse. Based on our early study, we also propose that ALS patients that inherit the mutation in the IL6 receptor gene may develop ALS that progresses faster and is more severe. This study will investigate specific mechanisms in mouse models.
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- Carol Milligan, PhD
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Academic Editor- Neuroscience Journal, Hindawi (present)
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Support NOT related to study: 1 R03 AI137866-01 (PI: Hawkins; Milligan, co-PI) 04-1-2018 to 03-31-20 National Institute of Health TDC: $100,000 Development of IL6 Trans-signaling Mouse Model as a Shared Resource This project is to develop a mouse model that lacks incorporates a single nucleotide change to promote increased shedding in the mouse IL6 receptor to create a model of human subjects who inherit the Il6R Ala allele. If successful the model will be used in research related to neurodegenerative diseases, asthma, cancer and cardiovascular diseases. Role: co-PI Overlap: None AL170130 (Hawkins, PI) 07/15/18-06/30/20 Department of the Army DC: $250,000 Generation of a Mouse Model to Investigate IL-6 Trans-signaling in ALS In this study, we are proposing that IL6 transsignaling plays a role in making ALS progression and severity worse. Based on our early study, we also propose that ALS patients that inherit the mutation in the IL6 receptor gene may develop ALS that progresses faster and is more severe. This studies utilizes mouse models to investigate specific mechanisms. Role: co-I Overlap: None NIH 5R25NS089458 08/01/2015- 07/31/2020 (NCE) National Institute of Health TDC Â 1,165,910 Training in Health Disparity Research for a Diverse Neuroscience Workforce This is a new MasterÂs Program specifically developed to broaden educational opportunities for individuals interested in pursuing a career in Health Disparities in Neuroscience-related Disorders (HDND). The overall goal is to train individuals who will contribute to expanding diversity in the Neuroscience work-force. Role: co-PI Overlap: None
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Blazeman Foundation for ALS (Milligan)
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- From the Department of Neurobiology and Anatomy (M.W.-K., M.R., J.S., P.A., M.M., C.M.); Department of Neurology (J.C., M. Cartwright); and Department of Biochemistry (G.A.H.), Wake Forest School of Medicine; Division of Public Health (C.L.), Department of Biostatistical Sciences, Wake Forest School of Medicine; Departments of Neurology and Neurobiology (R.B.), Barrow Neurological Institute & St. Joseph's Hospital and Medical Center; Department of Neurology (M. Cudkowicz), Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School; and Current Address Department of Pediatrics (M.M.), Nationwide Children's Hospital, Columbus OH.
- Correspondence
Dr. Milligan milligan{at}wakehealth.edu
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