Scott Q Harper PhD

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Professor


Nationwide Children's Hospital

The Harper Lab is focused on developing RNAi-based treatments for dominantly inherited neuromuscular disorders.  We are also pursuing basic mechanistic studies related to two such disorders:  FSH Muscular Dystrophy (FSHD) and Limb-Girdle Muscular Dystrophy Type 1A (LGMD1A). We use a broad range of tools, including molecular techniques, biochemistry, viral vectors, and mouse models of disease.

Selected Publications:

  • S.Q. Harper, M. Hauser, C.  DelloRusso, D. Duan, R.W. Crawford, S. Phelps, H.A. Harper, A.S. Robinson, J.F. Engelhardt, S.V. Brooks, and J.S. Chamberlain.  (2002) Modular flexibility of dystrophin:  Implications for gene therapy of DMD.  Nature Medicine, 8(3), 253-261.
  • H. Xia, Q. Mao, S.L. Eliason, S.Q. Harper, I.H. Martins, H.T. Orr, H.L. Paulson, L. Yang, R.M. Kotin, and B.L. Davidson.  RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. (2004) Nature Medicine10(8), 816-820.
  • S.Q. Harper, P.D. Staber, X. He, S.L. Eliason, I.H. Martins, L. Yang, H.L. Paulson, R.M. Kotin, and B.L. Davidson.  RNA interference improves behavioral and neuropathological abnormalities in a mouse model for Huntington’s disease. (2005)Proceedings of the National Academy of Sciences, USA.  102(16), 5820-5825.
  • J.L. McBride*, R.L. Boudreau*, S.Q. Harper* (shared first authorship), A. Mas Monteys, P.D. Staber, I. Martins, B. Gilmore, H. Burstein, R.W. Peluso, B. Polisky, B.J. Carter, and B.L. Davidson.  MicroRNA shuttles mitigate short-hairpin RNA mediated toxicity in the brain: Implications for therapeutic development of RNA interference.  (2008) Proceedings of the National Academy of Sciences, USA105(15):5868-73.
  • S.Q. Harper. Progress and challenges in RNA interference therapy for Huntington disease (2009) Archives of Neurology, 66(8): 933-938.
  • L.M. Wallace, S.E. Garwick, W. Mei, A. Belayew, F. Coppee, K.J. Ladner, D. Guttridge, J. Yang, and S.Q. Harper. DUX4, a candidate gene for Facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo. (2010) Annals of Neurology, (2011) Epub Oct 28; March;69(3):540-52.
  • L.M. Wallace, S.E. Garwick-Coppens, R. Rupler, and S.Q. Harper. RNA interference improves myopathic phenotypes in mice over-expressing FSHD Region Gene 1 (FRG1) (2011) Molecular Therapy, Nov;19(11):2048-54.
  • L.M. Wallace, J. Liu, J.S. Domire, S.E. Garwick-Coppens, S.M. Guckes, J.R. Mendell, K.M. Flanigan, and S.Q. Harper. RNA interference inhibits DUX4-induced muscle toxicity in vivo: Implications for a targeted FSHD therapy (2012) Molecular TherapyJuly:20(7):1417-23.
  • J. Liu and S.Q. Harper. (2012) RNAi-based gene therapy strategies for dominant limb girdle muscular dystrophies. Current Gene Therapy 12(4):307-314.
  • L.M. Wallace, A. Moreo, K.R. Clark, and S.Q. Harper. Dose dependent toxicity of humanized Renilla reniformis GFP (hrGFP) limits its utility as a reporter gene in mouse muscle (2013) In press at Molecular Therapy Nucleic Acids.

See also: http://www.osuchildrensmusclegroup.org/harper.shtml

Grants Awarded
Development of novel DUX4-targeted miR-675- based therapies for FSHD
Aug 1, 2020
Research - Translational
In our therapeutic strategies we aim to use gene and molecular tools (Adeno Associated Viral (AAV) vectors and pharmaceutical drugs) to increase the abundance of a specific microRNA targeting DUX4 in skeletal muscles, and thus, to reach our ultimate goal to cure FSHD.
DUX4 mRNA silencing using RNA editing by CRISPR-Cas13-ADAR2 and endogenous ADAR
Aug 1, 2020
Research - Translational
We hypothesize that DUX4 RNA editing can be a powerful tool for making changes in the DUX4 RNA, and by doing so we can make it less toxic to muscle cells.
Validation of a PPMO morpholino lead compound in an animal model of FSHD
Jun 1, 2015
Research - Translational
Dr. Harper will lead a team to test a DUX4-targeting compound in an animal model of FSHD.