Louise R. Rodino-Klapac, Ph.D.
The Ohio State University School of Medicine
of Pediatrics and Center for Gene Therapy
Nationwide Children's Research Institute
700 Children's Drive, Rm. WA3015
Columbus, OH 43205
Phone: (614) 355-2893
Education & Training:
King’s College, Wilkes-Barre, PA, 2000 BS in Biology
The Ohio State University 2005, Ph.D. in Molecular Genetics
The Research Institute at Nationwide Children’s Hospital, 2010, Postdoctoral Fellow
My laboratory is focused on developing gene therapy based vectors for the treatment of neuromuscular disorders. With emphasis on translating laboratory benchside research to the bedside, we are interested in addressing key issues such as transgene delivery, efficacy of gene expression, and immunogenicity; which all have the potential to affect clinical outcomes. One of our goals is to deliver recombinant adeno-associated virus (rAAV) mediated vectors by a vascular route to target multiple muscle groups. One such vector is micro-dystrophin as a potential treatment for Duchenne muscular dystrophy (DMD). Gene therapy based therapeutics for other forms of muscular dystrophy, Limb girdle muscular dystrophy type 2B [dysferlin (DYSF) deficiency] and the related type 2L (Anoctamin 5 (AN05) deficiency] are also a key initiative in my lab. Development of a gene delivery vector for DYSF deficiency using a novel approach with AAV5 is currently underway and future studies will focus on translating these pre-clinical studies to the clinic. We are testing the efficacy of gene transfer using a membrane repair assay in muscle isolated from animals treated with AAV5.DYSF. Pre-Clinical studies for AN05 are well underway including characterization of AN05 function and understanding loss of function mechanisms in both zebrafish and mouse models.
- Rodino-Klapac, LR, Janssen, PML, Montgomery, CL, Coley, BD, Chicoine, LG, Clark, KR and Mendell, JR. (2007) A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. Journal of Translational Medicine 5:45. PMID:17892583
- Rodino-Klapac, LR, Lee, JS, Mulligan, RC, Clark, KR and Mendell, JR. (2008) Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology 71:240-247.
- Rodino-Klapac, LR, Haidet, AM, Kota, J, Handy, C, Kaspar, BK, and Mendell, JR. (2009) Inhibition of Myostatin with Emphasis on Follistatin as a Therapy for Muscle Disease. Muscle and Nerve 39:283-96. PMID:19208403
- Mendell, JR, Rodino-Klapac, LR, Rosales-Quintero, X, Kota, J, Coley, BD, Galloway, G, Craenen, JM, Lewis, S, Malik, V, Shilling, CJ, Byrne, B, Conlon, T, Campbell, KJ, Bremer, WG, Viollet, L, Walker, CM, Sahenk, Z, Clark, KR. (2009) LGMD 2D gene therapy restores alpha-sarcoglycan and associated proteins. Annals of Neurology 66: 290-297. PMID:19798725
- Rodino-Klapac, LR, Montgomery, CL, Bremer, WG, Shontz, KM, Malik,V, Davis, N, Sprinkle, S, Campbell, KJ, Sahenk, Z, Clark, KR, Walker, CM, Mendell, JR, Chicoine, LG. (2010) Persistent expression of FLAG tagged micro-dystrophin in non-human primates with intramuscular and vascular delivery. Molecular Therapy. 18: 109-117. PMID:19904237
- Malik, V, Rodino-Klapac, LR, Viollet, L, Wall, C, King, W, Al-Dahhak, R, Lewis, S, Shilling, CJ, Kota, J, Serrano-Munuera, C, Hayes, J, Mahan, JD, . Campbell, KJ, Banwell, B, Dasouki, M, Watts, V, Sivakumar, K, Bien-Willner, R, Flanigan, KM, Sahenk, Z, Barohn, RJ, Walker, CM, Mendell, JR. (2010) Gentamicin-Induced Readthrough of Stop Codons in Duchenne Muscular Dystrophy. Annals of Neurology 67: 771-780. PMID:20517938
- Mendell, JR, Campbell, CJ, Rodino-Klapac, LR, Sahenk, Z, Shilling, C, Lewis, S, Bowles, D, Gray,S, Li, C, Galloway, G, Malik, V, Coley, B, Clark, KR, Li, J, Xiao, X, Samulski, J, McPhee, SW, Samulski, RJ, Walker, CM. (2010) Dystrophin Immunity Revealed by Gene Therapy in Duchenne’s Muscular Dystrophy. New England Journal of Medicine 363: 33-41. PMID:20925545
- Mendell, JR, Rodino-Klapac, LR, Rosales-Quintero, X, Kota, J, Coley, BD, Galloway, JM, Lewis, S, Malik, V, Shilling, CJ, Byrne, B, Conlon, T, Campbell, KJ, Bremer, WG, Taylor, LE, Flanigan, KM, Kota, J, Sahenk, Z, Walker, CM, Clark, KR. (2010) Sustained alpha-sarcoglycan gene expression after gene transfer in Limb-Girdle Muscular Dystrophy, Type 2D. Annals of Neurology 68: 629-638. PMID:21031578
- Rodino-Klapac LR, Montgomery CL, Mendell JR, Chicoine LG. (2011) AAV-mediated gene therapy to the isolated limb in rhesus macaques. Methods Mol. Biol. 709: 287-98. PMID:21194036
- Grose WG, Clark KR, Griffin DG, Shontz K, Malik V, Montgomery CL, Janssen, PM, Brown RJ, Mendell JR, Rodino-Klapac LR. (2012) Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency Following AAV5 Gene Transfer. PLoS One. 7(6):e39233. Epub 2012 Jun 15 PMID: 22720081