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Linda Kusner Linda Kusner
Research Professor of Pharmacology and Physiology
Research Professor of Genomics and Precision Medicine (Secondary)

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

Education

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

Biography

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. I have now devoted my research to understanding the autoimmune disease, Myasthenia Gravis. 

Additional Education

Case Western Reserve University, Post-doctorate 2004-2007
Saint Louis University, Neurology, Post-doctorate 2007

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
  • Xie Y, Meng Y, Li HF, Hong Y, Sun L, Zhu X, Yue YX, Gao X, Wang S, Li Y, Kusner LL, Kaminski HJ. GR gene polymorphism is associated with inter-subject variability in response to glucocorticoids in patients with myasthenia gravis. Eur J Neurol. 23(8):1372-9. Aug 2016. PMID: 27185333
  • Kaminski HJ, Himuro K, Alshaikh J, Gong B, Cheng G, Kusner LL. Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats. Front Physiol. 10; 7:524. Nov 2016. PMID: 27891095
  • Aguilo-Seara G, Xie Y, Sheehan JP, Kusner LL, Kaminski HJ. Ablation of IL-17 Expression Moderates Experimental Autoimmune Myasthenia Gravis Disease Severity. Cytokine. 2017 Aug; 96: 279-285. PMID: 28599246
  • Xie Y, Li HF, Sun L, Kusner LL, Wang S, Meng Y, Zhang X, Hong Y, Gao X, Li Y, Kaminski HJ. The Role of Osteopontin and its Gene on Glucorticoid Response in Myasthenia Gravis. Front Neurol. 2017 May 31; 8:230. PMID: 28620344
  • Kusner LL, Sengupta M, Kaminski HJ. Acetylcholine receptor antibody-mediated animal models of myasthenia gravis and the role of complement. Ann N Y Acad Sci. 2018 Feb. 1413(1):136-142. PMID: 29356015
  • Sengupta M, Wang BD, Lee NH, Marx A, Kusner LL, Kaminski HJ. MicroRNA and mRNA expression associated with ectopic germinal centers in thymus of myasthenia gravis. PLoS One. 2018 Oct 11; 13(10):e0205464. doi: 10.1371/journal.pone.0205464. eCollection 2018. PMID: 30308012
  • Kusner LL, Yucius K, Sengupta M, Sprague AG, Desai D, Nguyen T, Charisse K, Kuchimanchi S, Kallanthottathil R, Fitzgerald K, Kaminski HJ, Borodovsky A. Investigational RNAi Therapeutic Targeting C5 is Efficacious in Pre-Clinical Models of Myasthenia Gravis. Molecular Therapy - Methods & Clinical Development. 2019 May 10; 13: 484-492. doi: 10.1016/j.omtm.2019.04.009. eCollection 2019 Jun 14. PMID: 31193726.
  • Cron MA, Guillochon É, Kusner L, Le Panse R. Role of miRNAs in Normal and Myasthenia Gravis Thymus. Front Immunol. 2020 Jun 10;11:1074. doi: 10.3389/fimmu.2020.01074. PMID: 32587589; PMCID: PMC7297979.
  • Zhang X, Ciesielski M, Fenstermaker RA, Kaminski HJ, Kusner LL. The Presence of Survivin on B Cells from Myasthenia Gravis Patients and the Potential of an Antibody to a Modified Survivin Peptide to Alleviate Weakness in an Animal Model. J Immunol. 2020 Oct 1;205(7):1743-1751. doi: 10.4049/jimmunol.2000482. Epub 2020 Aug 24. PMID: 32839239; PMCID: PMC7504892.
  • Punga AR, Kusner L, Berrih-Aknin S, Le Panse R. Editorial: Advances in Autoimmune Myasthenia Gravis. Front Immunol. 2020 Aug 28;11:1688. doi: 10.3389/fimmu.2020.01688. PMID: 32983085; PMCID: PMC7484602.
  • Yue Y, Xu P, Liu Z, Sun X, Su J, Du H, Chen L, Ash RT, Smirnakis S, Simha R, Kusner L, Zeng C, Lu H. Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit. Sci Adv. 2021 Oct 22;7(43):eabf7467. doi: 10.1126/sciadv.abf7467. Epub 2021 Oct 22.
     

Research

The goal of my research is to understand the autoimmune process in order 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.  

To gain the understanding of the therapeutic efficacy in MG, I 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.

Grants

Targeted Therapy for Myasthenia Gravis
NIH-STTR/Arc Biotechnology
Role: PI
October 16, 2019 – September 1, 2021
The award is to determine the efficacy of targeted therapeutic constructs for myasthenia gravis.
 
Rare Disease Consortium, MGNet
NIH/MGFA/Concur MG
Role: Co-PI
October 1, 2019 – September 30, 2024
The consortium is created to promote the clinical trial readiness for therapeutics in myasthenia gravis, provide an avenue of biological sample collection and natural history of patients with myasthenia gravis.


Alexion Pharmaceuticals
Role: PI
November 29, in 2021 – February 28, 2023
The project will assess the efficacy of an antibody to C5 in experimental autoimmune myasthenia gravis.

Myasthenia Gravis Foundation of America
Role: PI
January 1, 2022 – December 31, 2023
Total cost: $110,000
The proposal supports the work of surviving expression in the B cells from myasthenia gravis patients.
 
GRO Biosciences
Role: PI
February 1, 2022 – May 1, 2023
The project will assess the glycosylation of peptides of the neuromuscular junction in myasthenia gravis.

Alynlam Parmaceutical
Role:  PI
September 15, 2022 - September 14, 2023
The project will assess complement inhibition in EAMG model.

MimiVax
NIH/STTR
Role:  PI
September 15, 2022 - September 14, 2023
The project will assess the humanized antibody to survivin in EAMG model.



 

Industry Relationships and Collaborations

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

  • ARC Biotechnology, LLC