Dean Burkin Lab

Dean J. Burkin, Ph.D.
Professor of Pharmacology and Pediatrics
Interim Chair, Department of Physiology and Cell Biology
Center for Molecular Medicine 203E
University of Nevada, Reno School of Medicine
1664 North Virginia Ave.,
Reno, NV 89557

Telephone: (775) 784-6288
Email: dburkin@med.unr.edu

Education
B.Sc. from Victoria University of Wellington, New Zealand
B.Sc. (1st class Hons) from Victoria University of Wellington, New Zealand
Ph.D. from the University of Colorado Health Sciences Center, USA
Postdoctoral, Cambridge University, England
Postdoctoral, University of Illinois Champaign-Urbana, USA

Research Team

Ryan Wuebbles, PhD., Research Assistant Professor
Marisela Dagda, MS., Research Associate
Hailey Hermann, MS., Graduate Student
Mariana Torres-Gonzales, Research Technician
Hailey Guerrero, Undergraduate Student
Lola Byrne, Undergraduate Student
Ellie Twedt, Undergraduate Student

Research Interests

The primary goal of my research is to understand the role the α7β1 integrin and laminin play in muscle development and disease. My laboratory studies on three genetic diseases:

 

  • Duchenne muscular dystrophy (DMD)
  • Laminin-α2 related congenital muscular dystrophy (LAMA2-CMD)
  • Integrin a7-related congenital muscular dystrophy (ITGA7-CMD)

 

The a7b1 integrin is a transmembrane receptor and prominent laminin-binding integrin in skeletal, smooth and cardiac muscle. The a7b1 integrin serves as a mechanosensor that acts to transduce mechanical stretch within the myomatrix to the cytoskeleton and signaling proteins within muscle. Using transgenic and knockout mouse models, we have shown the a7β1 integrin is a major modifier of disease progression in several muscular dystrophies including DMD and LAMA2-CMD. These studies support the idea that α7β1 integrin is a target for drug development and its enhancement will be therapeutic for fatal muscle diseases. Using a novel muscle-based assay and high throughput drug discovery, we have identified first-in-class a7 integrin-enhancing small molecules. These small molecules are being investigated as potential treatments for DMD and LAMA2-CMD. These compounds also serve as molecular probes to identify and dissect signaling pathways that regulate the α7β1 integrin in muscle.

 

Recently, we have identified patients with mutations in ITGA7, the gene encoding a7 integrin, who lack the α7β1 integrin. These patients have muscle weakness, respiratory dysfunction and a novel cardiac arrhythmia. Using a mouse model developed in my laboratory we are investigating the mechanisms by which the α7β1 regulates cardiac electrical function.   

 

Laminins are heterotrimeric proteins and critical components of the extracellular matrix throughout our bodies. Laminins are critical for maintaining cellular adhesion, communication, and structure. We have identified that Laminin-111, an isoform of laminin found in embryonic muscle and adult tissues, can increase the α7β1 integrin in mouse and human muscle cells. We have demonstrated Laminin-111 protein therapy can prevent muscle disease progression in mouse models of DMD and LAMA2-CMD. We have developed recombinant human Laminin-111 as a treatment modality for children with LAMA2-CMD.  We are investigating the mechanism(s) by which laminin isoforms regulate adhesion-signaling complexes in muscle.

Publications

    1. Bugiardini E, Nunes AM, Oliveira-Santos A, Dagda M, Fontelonga TM, Barraza-Flores P, Pittman AM, Morrow J, Parton M, Houlden H, Elliott PM, Syrris P, Maas R, Akhtar MM, Küsters B, Raaphorst J, Schouten M, Kamsteeg E, van Engelen B, Hanna MG, Phadke R, Lopes LR, Matthews E and Burkin DJ. (2022) Integrin α7 mutations cause adult-onset cardiac dysfunction in humans and mice. Journal of the American Heart Association. 11: e026494
    2. Oliveira-Santos A, Dagda M and Burkin DJ. (2022) Sunitinib inhibits STAT3 phosphorylation in cardiac muscle and prevents cardiomyopathy in the mdx mouse model of Duchenne muscular dystrophy. Human Molecular Genetics 31: 2358-2369.
    3. Barraza-Flores P, Bukovec KE, Dagda M, Conner BW, Oliveira-Santos A, Grange RW,Burkin DJ (2020). Laminin-111 protein therapy after disease onset prevents muscle disease in a mouse model of Laminin-a2-related congenital muscular dystrophy.  Human Molecular Genetics 13: 2162-2170
    4. Barraza-Flores P, Fontelonga TM, Wuebbles RD, Hermann HJ, Kornegay JN and Burkin DJ (2019). Laminin-111 protein therapy enhances muscle regeneration in the GRMD dog model of Duchenne muscular dystrophy. Human Molecular Genetics 28: 2686-2695
    5. Willmann R, Gordish-Dressman H, Meinen S, Ruegg MA, Yu Q, Nagaraju K, Kumar A, Girgenrath M, Coffey CBM, Cruz V, Van Ry P, Bogdanik L, Lutz C, Rutkowski A and Burkin DJ (2017). Improving reproducibility of phenotypic assessments in the dyW mouse model of laminin-a2 related congenital muscular dystrophy (LAMA2-CMD). Journal Neuromuscular Disorders 4: 115-126.
    6. *Wuebbles RD, Sarathy A, Kornegay J and Burkin DJ (2013). Laminin-a2 and a7 integrin are increased following prednisone treatment in the mdx and GRMD dog models of Duchenne muscular dystrophy. Disease Models and Mechanisms 6:1175-1184.

                         *This article was selected for an “In this Issue” highlight by the editors of DMM

    1. Burkin DJ and Wuebbles RD (2012). A molecular bandage for diseased muscle. Science Translational Medicine 4: 139fs19.

Full list of publications