Ohio State - Nationwide Children's Hospital - Research For Muscle Biology and Disease
 

 

Brian K. Kaspar , Ph.D.
Associate Professor

The Ohio State University School of Medicine
Department of Pediatrics
Nationwide Children's Research Institute
Investigator, Center for Childhood Cancer
700 Children's Drive, Rm. WA3022
Columbus, OH  43205

Office Phone: (614) 722-5085
Lab Phone: (614) 722-2875
Fax: (614) 355-5247
Email: Brian.Kaspar@NationwideChildrens.org
Website: http://www.ccri.net

Education & Training:
University of California-San Diego, La Jolla, CA, 2000 Ph.D. in Molecular Pathology
The Salk Institute for Biological Studies, La Jolla, CA, 2004 Postdoctoral Fellow Neuroscience and Gene Therapy

Research Interest:
The Kaspar Laboratory focuses on basic and translational studies related to neurological and neuromuscular disorders.  The laboratory has strengths in animal models of neurodegenerative and neuromuscular disease, gene delivery, and stem cell biology.  

A main focus of the Kaspar laboratory is centered on the mechanism(s) of neurodegeneration in Amyotrophic Lateral Sclerosis (ALS).  We employ rodent models of this disease to investigate various cell type involvements in disease onset and progression.  Furthermore, we are actively developing novel methods to deliver genes and therapies more efficiently to the nervous system and testing novel targets to combat this debilitating, lethal disease.

The laboratory also investigates the biological control of embryonic and adult derived stem cells.  Our current studies with stem cells are evaluating cell cycle regulation along with developing methods for intricate control of differentiation to defined cellular phenotypes, such as complex motor neurons.   

Finally, our laboratory works on muscle enhancing strategies in order to combat musculoskeletal disorders.  We have identified that follistatin is a potent antagonist of myostatin, and when delivered by a one-time gene delivery to skeletal muscle, enhances muscle size and mass.  Interestingly, our work has demonstrated that follistatin reduces the inflammatory environment in dystrophic muscles and induces improvements in functional strength in rodent models of Duchene Muscular Dystrophy.  We are currently involved with developing a human clinical trial for Inclusion Body Myositis with Dr. Jerry Mendell.

Selected Publications:

  • Palmer TD, Schwartz PH, Taupin P, Kaspar B, Stein SA, Gage FH. Cell culture. Progenitor cells from human brain after death. Nature. 2001 May 3;411(6833):42-3.
  • Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH, Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science, 22 Aug, 2003. 839-42.
  • Maheshri N, Koerber JT, Kaspar BK, Schaffer DV.  Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nature Biotechnology, 2006.  Feb 24; 198-204. 
  • Timothy M. Miller, Soo H. Kim, Mark Hester, Priya Umapathi, Hannah Arnson, Lisa Rizo, Jerry Mendell, Fred H. Gage, Don W. Cleveland, Brian K. Kaspar.  Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis.  Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51.
  • Miller TM, Smith RA, Kordasiewicz, Kaspar BK, Gene targeted therapies for the Central Nervous System. Archives of Neurology, 2008.  April; 65 (4) 447-51.
  • Haidet AM, Rizo L, Handy C, Umapathi P, Eagle A, Shilling C, Boue D, Martin P, Sahenk Z, Mendell JR, Kaspar BK, (2008) Long-term Enhancement of Skeletal Muscle Mass and Strength by Single Gene Administration of Myostatin Inhibitors, Proc Natl Acad Sci USA;105(11):4318-22.
  • Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK, (2009) Intravascular AAV9 preferentially targets neonatal-neurons and adult-astrocytes in CNS. Nature Biotechnology, 27; 59-65.
  • Hester ME, Song S, Miranda CJ, Eagle A, Schwartz PH, Kaspar BK, (2009) Two factor reprogramming of human neural stem cells into pluripotency, PLoS One,18;4(9):e7044.
  • Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK, (2009) Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN, Nat Biotechnol. 28:271-274.
  • Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK, (2009) Follistatin gene delivery enhances muscle growth and strength in nonhuman primates, Sci Transl Med., 1:6ra15.
  • Bevan AK, Hutchinson KR, Foust KD, Braun L, McGovern VL, Schmelzer L, Ward JG, Petruska JC, Lucchesi PA, Burghes AH, Kaspar BK, (2010) Early heart failure in the SMN{Delta}7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery, Hum Mol Genet., (In Press).
  • Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, Song S, Likhite S, Murtha MJ, Foust KD, Rao M, Eagle A, Kammesheidt A, Christensen A, Mendell JR, Burghes AH, Kaspar BK, (2011) Nat Biotechnol.;29(9):824-8
  • Bevan AK, Duque S, Foust KD, Morales PR, Braun L, Schmelzer L, Chan CM, McCrate M, Chicoine LG, Coley BD, Porensky PN, Kolb SJ, Mendell JR, Burghes AH, Kaspar BK, (2011) Mol Ther. (11):1971-80