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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 Dieog, 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.
- McCrate M and Kaspar BK, Physical Activity and Neuroprotection
in Amyotrophic Lateral Sclerosis, NeuroMolecular Medicine, 2008,
10 (2) 108-117
- Haidet AM, Rizo L, Handy C, Umapathi P, Eagle A, Shilling C, Boue
D, Martin P, Sahenk Z, Mendell JR, Kaspar BK, Long-term
Enhancement of Skeletal Muscle Mass and Strength by Single Gene Administration
of Myostatin Inhibitors, Proc Natl Acad Sci USA, 2008,
Mar 18;105(11):4318-22.
- Dodge JC, Yang W, Passini MA, Clarke J, Rizo L, Martin H, Hester
M, Kim SH, Wen R, Taksir TV, Griffiths DA, Cheng SH, Shihabuddin LS, Kaspar
BK. Cerebellar Nuclei injection of AAV targets the spinal
cord and improves motor function and prolonging survival in symptomatic
ALS mice. Molecular Therapy, June, 16(6):
1056-1064 2008.
- Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar
BK, Intravascular AAV9 preferentially targets neonatal-neurons
and adult-astrocytes in CNS. Nature Biotechnology,
27; 59-65 2009.
- Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK,
Mendell JR. Inhibition of myostatin with emphasis on follistatin
as a therapy for muscle disease. Muscle Nerve, EPub: Feb 10;39: 283-96.
2009.
- Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK, Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN, Nat Biotechnol. 28:271-274, 2009.
- 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, Follistatin gene delivery enhances muscle growth and strength in nonhuman primates, Sci Transl Med., 1:6ra15, 2009.
- Bevan AK, Hutchinson KR, Foust KD, Braun L, McGovern VL, Schmelzer L, Ward JG, Petruska JC, Lucchesi PA, Burghes AH, Kaspar BK, Early heart failure in the SMN{Delta}7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery, Hum Mol Genet., 2010 (In Press).
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