Dean Burkin Lab

Department of Pharmacology

Integrin and laminin-based therapies for the muscular dystrophies

The primary goal of my research program is to understand the role integrin receptors and the extracellular matrix play in neuromuscular development and disease. Using transgenic and knockout mice we have shown that the α7β1 integrin is a major modifier of disease progression in several muscular dystrophies including Duchenne Muscular Dystrophy (DMD) and Merosin-Deficient Congenital Muscular Dystrophy type 1A (MDC1A). These studies support the idea that the α7β1 integrin is a drug target for the treatment of these and potentially other fatal muscle diseases. Using a novel muscle-based assay and high throughput drug discovery, we have recently identified that laminin-111 protein can increase α7 integrin protein in mouse and human muscle cells. We have demonstrated laminin-111 protein therapy can improve muscle repair after damage and prevent muscle disease progression in mouse models of DMD and MDC1A. In addition, we have identified several integrin-enhancing small molecules that may be useful in the treatment of muscle disease and serve as molecular probes to identify and dissect signaling pathways regulated by the α7β1 integrin in normal and diseased muscle.

Selected Publications

  1. Van Ry P, Minogue P, Hodges B and Burkin DJ (2014). Laminin-111 improves muscle repair in a mouse model of Merosin Deficient Congenital Muscular Dystrophy. Human Molecular Genetics 23:383-96.
  2. Wuebbles RD, Sarathy A, Kornegay J and Burkin DJ (2013). Laminin-α2 and α7 integrin are increased following prednisone treatment in the mdx and GRMD dog models of Duchenne muscular dystrophy. Disease Models and Mechanisms ;6:1175-84. (This article was selected for an "In this Issue" highlight by the editors of DMM.)
  3. Marshall JL, Chou E, Oh J, Kwok A, Burkin DJ, and Crosbie-Watson RH (2012). Dystrophin and utrophin expression require sarcospan: loss of α7 integrin exacerbates a newly discovered muscle phenotype in sarcospan-null mice. Human Molecular Genetics 21:4378-4393.
  4. Burkin DJ and Wuebbles RD (2012). A molecular bandage for diseased muscle. Science Translational Medicine 4: 139fs19.
  5. Rooney JE, Knapp JR, Hodges, BL, Wuebbles RD and Burkin DJ (2012). Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy. American Journal of Pathology 4:1593-1602.
  6. Doe JA, Wuebbles RD, Allred ET, Rooney, JE, Elorza M and Burkin DJ. (2011). Transgenic overexpression of the α7 integrin reduces muscle pathology and improves viability in the dyW mouse model of MDC1A. Journal of Cell Science 124:2287-2297.
  7. Welser JV, Rooney JE, Cohen NC, Gurpur PB, Singer CA, Evans R, Haines BA, and Burkin DJ (2009). Myotendinous Junction Defects and Reduced Force Transmission in Mice that Lack α7 Integrin and Utrophin. American Journal of Pathology 175:1545-1554.
  8. Rooney RE, Gurpur PB and Burkin DJ (2009). Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. Proceedings of the National Academy of Sciences (USA) 106:7991-7996.
  9. Rooney J, Gurpur P, Yablonka-Reuveni Z and Burkin DJ (2009). Laminin-111 restores regenerative capacity in a mouse model for α7-integrin congenital myopathy. American Journal of Pathology 174:256-264. (This paper was selected for a press release by the Editors of the American Journal of Pathology.)
  10. Gurpur P, Liu J, Burkin DJ and Kaufman SJ (2009). Valproic Acid Activates the PI3K/Akt/mTOR Pathway in Muscle and Ameliorates Pathology in a Mouse Model of Duchenne Muscular Dystrophy. American Journal of Pathology 174:256-264.

For more publications: PubMed