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Linda Kusner

Linda Kusner

Associate Research Professor of Pharmacology & Physiology
Associate Research Professor of Integrative Systems Biology (Secondary)

Office Phone: 202-476-1229
Email:
Department: Pharmacology & Physiology

Education

  • B.S., Cleveland State University, 1988
  • PhD, Case Western Reserve University, 2004

Biography

I started my career as a research technician at the VA Medical Center in Cleveland. After several years of fascinating meandering through the fields of biological sciences, I decided it was time to go back to school. The location was obvious since I was already on the Case Western Reserve University campus working. I obtained a Ph.D. from Case Western Reserve University in the Department of Physiology and Biophysics. My thesis focus was on the role of GAPDH in Diabetic Retinopathy. After a postdoctoral fellowship position in Neurology studying myasthenia gravis, I took a position as an Assistant Professor at Saint Louis University in the Department of Ophthalmology in 2007. Due to my interest in skeletal muscle, I joined the Research Center for Genetic Medicine at Children’s National Medical Center. My research interests focused on the understanding of extraocular muscle physiology and response to disease.  By studying the unique environment and cell specificity found in the extraocular muscle, I hope to be able to manipulate skeletal muscle during the disease state to return it to proper function.

Additional Education

Case Western Reserve University, Post-doctorate 2004-2007
Saint Louis University, Neurology, Post-doctorate 2007
Saint Louis University, Ophthalmology, Assistant Professor 2007-2011
George Washington University, Pharmacology and Physiology, Assistant Professor 2011
Children’s National Medical Center, Research Center for Genetic Medicine, Assistant Professor 2011

Publications

  • Kaminski HJ, Kusner LL, Nash KV, Ruff RL.  The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris. Neurology 1995 Mar;45(3 Pt 1):516-8.
  • Kaminski HJ, Kusner LL, Block CH. Expression of acetylcholine receptor isoforms at extraocular muscle endplates. Investigative Ophthalmology & Visual Science, 1996 Feb;37(2):345-51.
  • Kusner LL, Kaminski HJ. Nitric oxide synthase is concentrated at the skeletal muscle endplate.  Brain Res 1996 Aug 19;730(1-2):238-42.
  • Kusner LL, Mygland A, Kaminski HJ.  Ryanodine receptor gene expression thymomas. Muscle Nerve 1998 Oct;21(10):1299-303.
  • Kusner LL, Kim E, Kaminski HJ.  Heme oxygenase-2 expression at rat neuromuscular junctions. Neurosci Lett 1999 Oct 8;273(3):143-6.
  • Richmonds CR, Boonyapisit K, Kusner LL, Kaminski HJ.  Nitric oxide synthase in aging rat skeletal muscle. Mech Ageing Dev 1999 Sep 8;109(3):177-89.
  • Sweeney WE Jr, Kusner L, Carlin CR, Chang S, Futey L, Cotton CU, Dell KM, Avner ED.  Phenotypic analysis of conditionally immortalized cells isolated from the BPK model of ARPKD.  Am J Physiol Cell Physiol 2001 Nov;281(5):C1695-705.
  • Porter JD, Merriam AP, Khanna S, Andrade FH, Richmonds CR, Leahy P, Cheng G, Karathanasis P, Zhou X, Kusner LL, Adams ME, Willem M, Mayer U, Kaminski HJ. Constitutive properties, not molecular adaptations, mediate extraocular muscle sparing in dystrophic mdx mice. FASEB J. 2003 May;17(8):893-5.
  • Kusner L, Carlin C. Potential role for a novel AP180-related protein during endocytosis in MDCK cells.  Am J Physiol Cell Physiol. 2003 Nov;285(5):C995-1008.
  • Kusner LL, Sarthy VP, Mohr S. Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase: a role in high glucose-induced apoptosis in retinal Muller cells. Invest Ophthalmol Vis Sci. 2004 May;45(5):1553-61.
  • Kaminski HJ, Kusner LL, Richmonds C, Medof ME, Lin F. Deficiency of decay accelerating factor and CD59 leads to crisis in experimental myasthenia. Exp Neurol. 2006 Dec;202(2):287-93.
  • Kusner LL, Kaminski HJ, Soltys J.  The Effect of Complement and its Regulation on Myasthenia Gravis Pathogenesis. Expert Review of Clinical Immunology. 2008 Jan; 4(1): 43-52.
  • Soltys J, Kusner LL, Young A, Richmonds C, Hatala D, GongB, Shanmugavel V, Kaminski HJ. Novel Complement Inhibitor (rEV576) Limits Severity of Experimentally Acquired Myasthenia Gravis. Annals of Neurology. 2009 Jan;65(1):67-75.
  • Kusner LL, Young A, Tjoe S, Kaminski HJ. Perimysial fibroblasts of extraocular muscle are as unique as the muscle fibers. Investigative Ophthalmology & Visual Science, 2010 Jan; 51(1):192-200.
  •  Kusner LL, Kaminski HJ. The Role of Complement in Experimental Autoimmune Myasthenia Gravis. Annals of New York Academy of Sciences. Dec 2012;1274(1):127-132. PMID: 23252907
  • Kaminski HJ, Kusner LL, Wolfe, GI, Aban I, Minisman G, Conwit R, Cutter G. Biomarker development for myasthenia gravis. Myasthenia Gravis. Annals of New York Academy of Sciences. Dec 2012;1275(1):101-106. PMID: 23278584
  • Kusner LL, Halperin JA, Kaminski HJ. Cell Surface Complement Regulators Moderate Experimental Myasthenia Gravis Pathology. Muscle Nerve. 2013 Jan;47(1):33-40. 23042232. PMID: 23042232
  • Kusner LL, Satija N, Cheng G, Kaminski HJ. Targeting Therapy to the Neuromuscular Junction: Proof of Concept. Muscle  Nerve. 2013 Aug 27. doi: 10.1002/mus.24057. PMID: 24037951
  • Kusner LL, Ciesielski MJ, Marx A, Kaminski HJ, Fenstermaker RA. Survivin as a therapeutic target for antibody-mediated autoimmunity. PLoS One. 2014 Jul 22;9(7):e102231. PMID: 25050620
  • Sengupta M, Cheema A, Kaminski HJ, Kusner LL, Muscle Study Group. Metabolomic Response to Chronic Corticosteroid Treatment. PLoS One. 2014 Jul 17;9(7):e102635. PMID: 25032816
  • Zhou Y, Kaminski HJ, Gong B, Cheng G, Feuerman JM, Kusner L. RNA Expression Analysis of Passive transfer model of Myasthenia Gravis Supports Extraocular Muscle as a Unique Immunological Environment. Invest Ophthalmol Vis Sci. 2014 Jun 10;55(7):4348-59. PMID: 24917137
  • LiY, Tu Z, Qian S, Fung JJ, Markowitz SD, Kusner LL, Kaminski HJ, Lu L , Lin F. Myeloid-derived suppressor cells as a potential therapy for experimental autoimmune myasthenia gravis. J Immunol. 2014 Sep 1;193(5):2127-34. PMID: 25057008
  • Losen M, Martinez-Martinez P, Molenaar PC, Lazaridis K, Tzartos S, Brenner T, R Duan R, Luo L, Lindstrom J, Kusner L. Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors- recommendations for methods and experimental designs. Experimental Neurology. 270:18-28. Aug 2015. PMID: 25796590
  • Tuzun E, Berrih-Aknin S,  Brenner T, Kusner LL, Le Panse R, Yang H, Tzartos S, Christadoss P. Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization. Experimental Neurology. 270:11-7. Aug 2015. PMID: 25697844
  • Kusner LL, Losen, M, Lindstrom J; Tzartos S, Lazaridis K, Martinez-Martinez P. Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs. Experimental Neurology. ;270:3-10. Aug 2015. PMID: 25743217
  • Kusner LL, Kaminski HJ. Special issue on standardization of preclinical evaluation of animal models for myasthenia gravis. Exp Neurology 2015;270:1-2. PMID: 26071136
  • Xie Y, Li H-F, Jiang B, Li Y, Kaminski HJ, Kusner LL. Plasma IL-17 levels stratify across myasthenia gravis patient subtypes. Cytokines 78:44-46. 2016. PMID: 26618234

Grants

Myasthenia Gravis Foundation of Illinois                                    9/2015-9/2016
Evaluation of IL-17A as a Therapeutic Target for Myasthenia Gravis.
Role: Co-Principal Investigator
$80,000/yr
Preclinical studies of IL-17 role in pathogenesis of myasthenia gravis
 
Myasthenia Gravis Foundation of America                            7/01/2014-12/30/2015
Role: Principal investigator
Total cost: $50,000
The grant supports the investigation of survivin expression in Myasthenia gravis.
 
Evaluation of Novel Agent for Experimental Myasthenia      11/01/2014 – 10/31/2015
Alnylam, Inc.
Role: Principal investigator
Total cost: $40,000/yr
The goal of the grant is to evaluate a novel agent as a treatment for myasthenia gravis in animal models.
 
RFA_CRI_CTSI-CN                                                               1/01/2013-12/31/2013
Principal Investigator: Robert Avery
Co-Investigator: Linda L. Kusner
Total cost: $40,000
The grant supports the identification of biomarkers in pediatric ocular myasthenia gravis patients.

Research

The goal of my research is to improve therapy for patients with myasthenia gravis. Towards this goal I have pursued novel treatment approaches by targeting complement inhibition to the neuromuscular junction. The targeting of a complement inhibitor to the neuromuscular junction has led to a patent by the US government. I have also investigated the development of agents that suppress anti-apoptotic signals in autoreactive cells. My resent studies demonstrate B cells in patients with myasthenia gravis express inhibitor of apoptotic proteins which may allow for their survival and secretion of autoantibodies. By elimination of these specific B cells in animal models, I have shown the reduction in autoantibody titers. Through these two diverse approaches, not only is the complexity of the disease recognized but the hope of a therapeutic that can benefit patients with myasthenia gravis.  

Through my work on the Executive Committee of the Myasthenia Gravis Foundation of America’s Medical-Scientific Advisory Board, I have worked closely with clinicians and have appreciated the need for effective biomarkers to assess pre-clinical drug screening and more rigorously evaluate response in clinical trials. I am now championing an international effort to foster standard development for preclinical research in myasthenia gravis. I recently directed a conference supported by the NIH and the MG Foundation of America for the development of such standards. These efforts will allow for an increase in therapeutic development and the successful progression to clinical trials.

Publications

View publications by this faculty member from January 1, 2013 - present

Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.

Industry Relationships and Collaborations

This faculty member (or a member of their immediate family) has a significant financial interest with the healthcare related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.

  • None