Brian K. Kaspar, Ph.D.

Brian K. Kaspar, Ph.D. is Principal Investigator in The Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital and Associate Professor in the Department of Pediatrics and Department of Neuroscience at The Ohio State University College of Medicine.

Gender:

• Male

Languages Spoken:

• English

Research Center:

• Center for Gene Therapy

Areas of 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.

Post Doctoral

• University of California, San Diego
  Date Completed: 06/30/2003

Post Doctoral

• Salk Institute for Biological Studies
  Date Completed: 06/30/2004

• Jukkola PI, Rogers JT, Kaspar BK, Weeber EJ, Nishijima I. 2011. Secretin deficiency causes impairment in survival of neural progenitor cells in mice.  Hum Mol Genet. (IF: 7.386) (Formally Accepted)
• Peterson JM, Kline W, Canan BD, Ricca DJ, Kaspar B, Delfín DA, Dirienzo K, Clemens PR, Robbins PD, Baldwin AS, Flood P, Kaumaya P, Frietas M, Kornegay JN, Mendell JR, Rafael-Fortney JA, Guttridge DC, Janssen PM. 2011. Peptide-based inhibition of NF-?B rescues diaphragm muscle contractile dysfunction in a murine model of Duchenne muscular dystrophy.  Molecular Medicine. (IF: 5.020)
• An MC; Lin W; Yang J; Dominguez B; Padgett D; Sugiura Y; Aryal P; Gould TW; Oppenheim RW; Hester ME; Kaspar BK; Ko CP; Lee KF. 2010. Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.  Proceedings Of The National Academy Of Sciences Of The United States Of America. Vol. 107, no. 23. (June 8): 10702. (IF: 9.432)
• Foust KD; Wang X; McGovern VL; Braun L; Bevan AK; Haidet AM; Le TT; Morales PR; Rich MM; Burghes AH; Kaspar BK. 2010. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.  Nature Biotechnology. Vol. 28, no. 3. (March 1): 271. (IF: 27)
• Sahenk Z, Galloway G, Edwards C, Malik V, Kaspar BK, Eagle A, Yetter B, Forgie A, Tsao D, Lin JC. 2010. TrkB and TrkC agonist antibodies improve function, electrophysiologic and pathologic features in Trembler J mice.  Exp Neurol. Vol. 224, no. 2. : 495-506. (IF: 3.914)
• Petruska JC, Kitay B, Boyce VS, Kaspar BK, Pearse DD, Gage FH, Mendell LM. 2010. Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult rats.  Eur J Neurosci. Vol. 32, no. 6. : 997-1005. (IF: 3.418)
• Dodge JC, Treleaven CM, Fidler JA, Hester M, Haidet A, Handy C, Rao M, Eagle A, Matthews JC, Taksir TV, Cheng SH, Shihabuddin LS, Kaspar BK. 2010. AAV4-mediated expression of IGF-1 and VEGF within cellular components of the ventricular system improves survival in familial ALS mice.  Mol Ther. Vol. 18, no. 12. : 2075-2084. (IF: 6.239)
• Haidet AM, Mendell JR, Kaspar BK. 2010. Could gene therapy be the future for muscular dystrophy?.  Therapy. Vol. 7, no. 3. : 287-290. (IF: 0.421)
• Bevan AK, Hutchinson KR, Foust KD, Braun L, McGovern VL, Schmelzer L, Ward JG, Peturska JC, Lucchesi PA, Burghes AH, Kaspar BK. 2010. Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery.  Hum Mol Genet. Vol. 19, no. 20. : 3895-3905. (IF: 7.386)
• Kota Janaiah, Handy Chalonda R, Haidet Amanda M, Montgomery Chrystal L, Eagle Amy, Rodino-Klapac Louise R, Tucker Danielle, Shilling Christopher J, Therlfall Walter R, Walker Christopher M, Weisbrode Steven E, Janssen Paul ML, Clark Reed K, Sahenk Zarife, Mendell Jerry R, Kaspar Brian K. 2009. Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates.  Science. Vol. 1, no. 6 6ra15. (November 11).
• Hester M, Foust K, Kaspar RW, Kaspar BK. AAV as a gene transfer vector for the treatment of neurological disorders: Novel treatment thoughts for ALS.  Current Gene Therapy, no. in press. (IF: 4.45) (In press)
• Kaspar RW, Wills CE, Kaspar BK. 2009. Gene therapy and informed consent decision making: nursing research directions.  Biol Res Nurs. Vol. 1, no. 11. (July): 98-107.
• Excoffon KJ, Koerber JT, Dickey DD, Murtha M, Keshavjee S, Kaspar BK, Zabner J, Schaffer DV. 2009. Directed evolution of adeno-associated virus to an infectious respiratory virus.  Proc Natl Acad Sci USA. Vol. 106, no. 10. (March 10): 3865-3870. (IF: 12.3)
• Rodino-Klapac L, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. 2009. Inhibition of myostatin with emphasis on follistatin as therapy for muscle disease.  Muscle Nerve. Vol. 39: 283-296.
• Hester M, Song SW, Miranda C, Eagle A, Schwartz P, Kaspar BK. Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency.  PLos One. (In press)
• Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. 2009. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.  Nat Biotechnol., no. Epub 2008 Dec 21. (IF: 22.848)
• Foust Kevin D, Kaspar Brian K. 2009. Over the barrier and through the blood to CNS delivery we go.  Cell Cycle. Vol. 8, no. 24: 16-17.
• Brian K. Kaspar. RNA Interference Techniques. In Neuroscience Methods. Edited by Scott Q. Harper. Totowa, New Jersey, United States: Humana/Springer Press. (Forthcoming)
• Kaspar BK. 2008. Mesenchymal stem cells as trojan horses for GDNF delivery in ALS.  Mol Ther.. Vol. 16, no. 12. (December): 1905-1906. (IF: 5.862)
• Kim ML, Chandrasekharan K, Glass M, Shi S, Stahl MC, Kaspar B, Stanley P, Martin PT. 2008. O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors.  Mol Cell Neurosci.. Vol. 39, no. 3. (November): 452-464. (IF: 3.994)
• Haidet, Amanda, M; Rizo, Liza; Handy, Chalonda; Umapathi, Priya; Eagle, Amy; Shilling, Chris; Boue, Daniel; Martin, Paul, T; Sahenk, Zarife; Mendell, Jerry, R; Kaspar, Brian K. 2008. Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors.  Proceedings of the National Academy of Sciences of the United States of America. Vol. 105, no. 11: 4318.
• Dodge, James, C; Haidet, Amanda, M; Yang, Wendy; Passini, Marco, A; Hester, Mark; Clarke, Jennifer; Roskelley, Eric, M; Treleaven, Christopher, M; Rizo, Liza; Martin, Heather; Kim, Soo, H; Kaspar, Rita; Taksir, Tatyana, V; Griffiths, Denise, A; Cheng, Seng, H; Shihabuddin, Lamya, S; Kaspar, Brian K. 2008. Delivery of AAV-IGF-1 to the CNS extends survival in ALS mice through modification of aberrant glial cell activity.  Molecular therapy : the journal of the American Society of Gene Therapy. Vol. 16, no. 6.
• Miller, Timothy, M; Smith, Richard, A; Kordasiewicz, Holly; Kaspar, Brian K. 2008. Gene-targeted therapies for the central nervous system.  Archives of neurology. Vol. 65, no. 4.
• McCrate ME, Kaspar BK. 2008. Physical activity and neuroprotection in amyotrophic lateral sclerosis. Review.  Neuromolecular Med.. Vol. 10, no. 2: 108-117. (IF: 2.483)
• Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR. 2007. Gene therapy for duchenne muscular dystrophy: expectations and challenges.  Archives of Neurology. Vol. 64, no. 9: 1236-1241.
• Kaspar, Ray, Senut, Suhr, Gage. 2007. Ex Vivo and In Vivo Gene Delivery to the Brain. In Current Protocols in Human Genetics. n/a: n/a.
• Miller, Timothy, M; Kim, Soo, H; Yamanaka, Koji; Hester, Mark; Umapathi, Priya; Arnson, Hannah; Rizo, Liza; Mendell, Jerry, R; Gage, Fred, H; Cleveland, Don, W; Kaspar, Brian K. 2006. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America. Vol. 103, no. 51. (December 19): 19546-19551.
• Maheshri, Narendra; Koerber, James, T; Kaspar, Brian, K; Schaffer, David V. 2006. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors.  Nature biotechnology. Vol. 24, no. 2. (February 24): 198-204.
• Kaspar BK and Gage FH. 2006. Gene Therapy and Neurological Disorders. In Gene Therapy. Edited by Pedro Lowenstein. San Diego: Alden International, Taylor and Francis Books. 33-37.
• Borrell, Victor; Kaspar, Brian, K; Gage, Fred, H; Callaway, Edward M. 2006. In vivo evidence for radial migration of neurons by long-distance somal translocation in the developing ferret visual cortex.  Cerebral cortex (New York, N.Y. : 1991). Vol. 16, no. 11: 1571-1583.
• Kaspar BK. 2006. Neural repair: regeneration and functional recovery: Gene therapy: direct viral delivery. In New Encyclopedia of Neuroscience. Edited by Larry Squire. n/a: n/a.
• Koerber, James, T; Maheshri, Narendra; Kaspar, Brian, K; Schaffer, David V. 2006. Construction of diverse adeno-associated viral libraries for directed evolution of enhanced gene delivery vehicles.  Nature protocols. Vol. 1, no. 2: 701-706.
• Lee GK, Maheshri N, Kaspar BK, Schaffer DV. 2005. PEG Conjugation Mederately Protects Adeno-Associated Viral Vectors Against Antibody Neutralization.  Biotechnology and Bioengineering. Vol. 92, no. 1. (October): 24-34.
• Kaspar, Brian, K; Frost, Lindsay, M; Christian, Lindsey; Umapathi, Priya; Gage, Fred H. 2005. Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis.  Annals of neurology. Vol. 57, no. 5. (May): 649-655.
• Kaspar, Brian, K; Roth, David, M; Lai, N Chin; Drumm, Jeffrey, D; Erickson, Dawn, A; McKirnan, M Dan; Hammond, H Kirk. 2005. Myocardial gene transfer and long-term expression following intracoronary delivery of adeno-associated virus.  The journal of gene medicine. Vol. 7, no. 3: 316-324.
• Miller, Timothy, M; Kaspar, Brian, K; Kops, Geert, J; Yamanaka, Koji; Christian, Lindsey, J; Gage, Fred, H; Cleveland, Don W. 2005. Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis.  Annals of neurology. Vol. 57, no. 5: 773-776.
• Hsieh, Jenny; Aimone, James, B; Kaspar, Brian, K; Kuwabara, Tomoko; Nakashima, Kinichi; Gage, Fred H. 2004. IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.  The Journal of cell biology. Vol. 164, no. 1. (January): 111-122.
• Kaspar, Brian, K; Llado, Jeronia; Sherkat, Nushin; Rothstein, Jeffrey, D; Gage, Fred H. 2003. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Cited 186 times.  Science (New York, N.Y.). Vol. 301, no. 5634. (August 22): 839-842.
• South, Samantha, M; Kohno, Tatsuro; Kaspar, Brian, K; Hegarty, Deborah; Vissel, Bryce; Drake, Carrie, T; Ohata, Megumi; Jenab, Shirzad; Sailer, Andreas, W; Malkmus, Shelle; Masuyama, Takashi; Horner, Philip; Bogulavsky, Johanna; Gage, Fred, H; Yaksh, Tony, L; Woolf, Clifford, J; Heinemann, Stephen, F; Inturrisi, Charles E. 2003. A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain.  The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 23, no. 12. (June): 5031-5040.
• Lai, Karen; Kaspar, Brian, K; Gage, Fred, H; Schaffer, David V. 2003. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Cited 168 times.  Nature neuroscience. Vol. 6, no. 1. (January 6): 21-27.
• Lie, D Chichung; Dziewczapolski, Gustavo; Willhoite, Andrew, R; Kaspar, Brian, K; Shults, Clifford, W; Gage, Fred H. 2002. The adult substantia nigra contains progenitor cells with neurogenic potential. Cited 145 times.  The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 22, no. 15. (August 1): 6639-6649.
• Kaspar, Brian, K; Vissel, Bryce; Bengoechea, Tasha; Crone, Steven; Randolph-Moore, Lynne; Muller, Rolf; Brandon, Eugene, P; Schaffer, David; Verma, Inder, M; Lee, Kuo-Fen; Heinemann, Stephen, F; Gage, Fred H. 2002. Adeno-associated virus effectively mediates conditional gene modification in the brain. Cited 41 times.  Proceedings of the National Academy of Sciences of the United States of America. Vol. 99, no. 4. (February 19): 2320-2325.
• Kaspar, Brian, K; Erickson, Dawn; Schaffer, David; Hinh, Linda; Gage, Fred, H; Peterson, Daniel A. 2002. Targeted retrograde gene delivery for neuronal protection. Cited 55 times.  Molecular therapy : the journal of the American Society of Gene Therapy. Vol. 5, no. 1. (January 5): 50-56.
• Palmer, T, D; Schwartz, P, H; Taupin, P; Kaspar, B; Stein, S, A; Gage, F H. 2001. Cell culture. Progenitor cells from human brain after death. Cited 170 times.  Nature. Vol. 411, no. 6833. (May 3): 42-43.
• Senut, M, C; Suhr, S, T; Kaspar, B; Gage, F H. 2000. Intraneuronal aggregate formation and cell death after viral expression of expanded polyglutamine tracts in the adult rat brain.  The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 20, no. 1. (January 1): 219-229.
• Ueba, T; Kaspar, B; Zhao, ; XGage, F H. 1999. Repression of human fibroblast growth factor 2 by a novel transcription factor.  The Journal of biological chemistry. Vol. 274, no. 15. (April 9): 10382-10387.
• Donahue BA, McArthur JG, Spratt SK, Bohl D, Lagarde C, Sanchez l, Kaspar BK, Sloan BA, Lee YL, Danos O, Snyder RO. 1999. Selective uptake and sustained expression of AAV vectors following subcutaneous delivery.  J Gene Med. Vol. 1, no. 1. (February): 31-42.
• Snyder, R, O; Spratt, S, K; Lagarde, C; Bohl, D; Kaspar, B; Sloan, B; Cohen, L, K; Danos, O. 1997. Efficient and stable adeno-associated virus-mediated transduction in the skeletal muscle of adult immunocompetent mice.  Human gene therapy. Vol. 8, no. 16. (November 1): 1891-1900.
• Brian Kaspar. filed 2005. (patent pending) Targeted Retrograde Gene Delivery for Neuronal Protection (European, United States). patent no. 6,998,118.
• Brian Kaspar. filed 2006. (patent pending) Mutant Adeno-Associated Virus Virions and Methods of Use Thereof (United States, European, Japanese).
• Brian Kaspar. filed 2005. (patent pending) Targeted Retrograde Gene Delivery to Motor Neurons (European, United States). patent no. 7,101,540.
• Brian Kaspar. filed 2009. (patent pending) AAV and Gene Delivery for Muscle Enhancing Agents. Submitted USPO.
• Brian Kaspar. filed 2009. (patent pending) AAV9 Vascular Delivery for Bypassing the Bolld Brain Barrier (United States, European).