Pam Van Ry
BS, University of Nevada, Reno 2010
Ph.D., University of Nevada, Reno 2014
Postdoctoral Research Fellow, University of Nevada School of Medicine 2014-2017
Identification of Protein Therapies for Muscular Dystrophy
The muscular dystrophies are a group of progressive degenerative muscle wasting diseases that vary in age of onset, phenotype, cause, severity and life span. Many of the treatment options for these diseases have not resulted in substantial quality of life treatment options desperately needed for patients and families. The goal of my lab is to identify protein therapies for several different types of muscular dystrophies. Once a therapy is identified, known endpoint markers for specific muscular dystrophies will be used to determine efficacy and mechanism. Dysferlinopathy is caused by mutations in the DYSF gene (encoding dysferlin protein) and is characterized by the following: delayed removal of necrotic muscle fibers, loss of calcium sensitivity leading to signaling mis-regulation, increased inflammatory infiltrate, muscle atrophy, malformation of transverse tubule structure and defective membrane repair. The role dysferlin plays in membrane resealing is well established, however research shows that dysferlin has multiple roles in skeletal muscle, many of which still need to be elucidated. The lack of treatment options for dysferlinopathy patients requires increased research to decrease disease progression. Galectin-1 is expressed in diverse tissues intra and extracellularly with tissue and pathogenic specificity. Glectin-1 is known to modulate the immune system, tumor progression, regeneration of central nervous system after injury, hypoxia, and vascularization. Research has shown that mdx mice treated with recombinant Galectin-1 display improved sarcolemma stability, reduced muscle pathology, improved muscle repair, and increased angiogenesis. These results indicate Galectin-1 is an exciting, new biologic therapy for the treatment of DMD. Since Galectin-1 has been shown to possess a diverse set of beneficial activities, we believe this biologic could be used to modify disease progression not only in DMD but also in other types of muscular dystrophy. My lab will test the hypothesis that Galectin-1 will improve the removal of necrotic muscle fibers, provide a network for the stabilization of stress-induced calcium signaling and formation in transverse tubules membrane, improves muscle strength and modulate immune response in mouse models of dysferlinopathy and other muscular dystrophies. To accomplish the goals of my lab, students will learn to use a variety of histological, biomolecular, biochemical and physiological techniques, including immunohistochemistry, bright field skeletal muscle histology, polymerase chain reactions, cell and tissue culture, protein purification and quantification, along with evaluation of cardiac and skeletal muscle physiological techniques. As a student in my lab you will learn about current issues in the field of muscle disease. By learning the techniques used in my lab, students will be able to formulate and solve important research questions which will have translational impact on patients and families. Students showing dedication will also get the opportunity to present data at local and international meetings, prepare, write and submit manuscripts to peer-reviewed journals. Research experience is a valued tool for any student to obtain setting them apart from their colleagues. I encourage undergraduate students to apply for an opportunity to gain research experience in my laboratory. I welcome all motivated undergraduates showing an interest in gaining research experience.
Van Ry, P.M., Minogue, P., Hodges, B.L., and Burkin, D.J. (2014). Laminin-111 improves muscle repair in a mouse model of merosin-deficient congenital muscular dystrophy. Hum Mol Genet 23, 383-396.
- Van Ry, P.M., Wuebbles, R.D., Keys, M., and Burkin, D.J. (2015). Galectin-1 protein therapy prevents pathology and improves muscle function in the mdx mouse model of Duchenne muscular dystrophy. Mol Ther.
- Griffiths, G.S., Doe, J., Jijiwa, M., Van Ry, P., Cruz, V., de la Vega, M., Ramos, J.W., Burkin, D.J., and Matter, M.L. (2015). Bit-1 is an essential regulator of myogenic differentiation. J Cell Sci 128, 1707-1717.
- Doe, Jinger, Kaindl, Angela M., Jijiwa, Mayumi, de la Vega, Michelle, Hu, Hao, Griffiths, Genevieve, Fontelonga, Tatiana M., Barraza, Pamela, Cruz, Vivian, Van Ry, Pam, Ramos, Joe W., Burkin, Dean J., and Matter, Michelle L. (2017). PTRH2 gene mutation causes progressive congenital skeletal muscle pathology.Hm Mol Genet
- Lewon, Matthew, Peters, C.M., Van Ry, P.M., Burkin, D.J., Hunter, K.H., and Hayes, L.J., (May, 2017). Evaluation of the behavioral characteristics of the mdx mouse model of duchenne muscular dystrophy through operant conditioning procedures. Behavioral Processes.
- Van Ry, P.M., Fontelonga, T., Barraza-Flores, P., Sarathy, A., Nunes, A., and Burkin, D.J. (June, 2017). ECM-Related Myopathies and Muscular Dystrophies: Pros and cons of Protein Therapies. Comprehensive Physiology.
- Willmann, R., Gordish-Dressman,H., Meinen, S., Rüegg, M.A., Yu, Q., Nagaraju, K., Ayar Kumar, Girgenrath, S., Coffey, C., Cruz, V., Van Ry, P.M., Burkin, D.J., Bogdanik, L., Lutz, K., Rutkowski, A. (May, 2017). Improving reproducibility of phenotypic assessments in the DyW mouse model of Laminin-α2 related Congenital Muscular Dystrophy. Journal of Neuromuscular Disease.