University of Miami >> Miller School of Medicine >> Office of Graduate Studies >> Faculty Research >> Faculty Research Detail

Justin M. Percival, Ph.D.

Assistant Professor of Molecular and Cellular Pharmacology

305-243-7303 (office)

305-243-4555 (fax)

RMSB 6088

Curriculum Vitae
1994                B.Sc., Biochemistry and Chemistry, Victoria University, Wellington, New Zealand
2003                Ph.D ., University of Sydney, Sydney, NSW, Australia
2003                Postdoctoral Fellow, Department of Physiology and Biophysics, University of Washington, Seattle, WA
2009                Research Assistant Professor, Department of Physiology and Biophysics, University of Washington
2012-present   Assistant Professor
Honors and Awards

2009               Howard Hughes Medical Institute Future Faculty Fellows Teaching Apprenticeship
2009               NIH/ Muscular Dystrophy Association /Child Neurological Society Young Investigator Award
2008               ASBMB Postdoctoral Travel Fellowship
2008               NIH/MDA Postdoctoral Poster Prize (New Directions in Skeletal Muscle Biology, New Orleans)
2007-2010      Muscular Dystrophy Association Career Development Grant.


Research Interests
The free radical gas, nitric oxide (NO) is a pivotal signaling messenger. NO was named “Molecule of the Year” in 1992 by the journal Science and the discovery that NO plays a central role in cardiovascular system function led to a Nobel Prize for Drs Furchgott, Ignarro and Murad in 1998. Since then, NO has proven to be an even more versatile messenger, performing important roles in many systems including the nervous, immune and motor systems.
In the Percival lab, we study NO signaling in normal and diseased skeletal and cardiac muscle. We depend on strong healthy skeletal muscle for movement and breathing and the heart for pumping blood.  Our primary interest is the function of NO synthesized by the enzyme neuronal nitric oxide synthase (nNOS). The functions of nNOS in muscle, particularly the less common splice variants, remain to be fully understood. We focus on the canonical NO-cGMP mode of signaling, where NO acts to stimulate cGMP synthesis by soluble guanylyl cyclase (sGC), a major receptor for NO. cGMP then in turn binds and activates downstream targets such as protein kinase G and ion channels (Figure 1). 

For an overview of Dr. Percival’s research program please see his interview by International INNOVATION magazine posted at ResearchGate: 

There are at least four splice variants of nNOS (nNOSα, nNOSβ, nNOSγ and nNOSμ). In skeletal muscle, nNOSμ was thought to be the only nNOS expressed; however we recently found that nNOSβ and sGC were expressed at the Golgi complex in muscle cells (Figure 2).  Both nNOSμ and nNOSβ isoforms are necessary for optimal exercise performance.  The mechanisms governing exercise capacity are not only important for understanding the limits of athletic performance, they are important because they are inextricably linked with human longevity. Furthermore, nNOSμ may not only regulate exercise capacity, it may also act as an “activity sensor” that initiates different signaling programs in an adaptive response to inactivity or endurance type exercise. For a more detailed description of current knowledge about nNOS function in skeletal muscle please read our 2011 review in Biophysical Reviews listed in the Publications section.
Abnormalities in nNOS signaling are a common pathogenic feature of many neuromuscular diseases including limb girdle and Duchenne/Becker muscular dystrophies. We use the mdx mouse model of Duchenne/Becker muscular dystrophy to understand the changes in nNOS function and to develop potential NO-based treatments for muscular dystrophy. We have found that pharmacologically enhancing NO-cGMP signaling, using drugs such as Viagra®,  is powerful for reducing dystrophic muscle disease.


To better understand nNOS-cGMP signaling, the Percival lab is focused on addressing the following questions:
1. What happens when muscle runs out of gas?
Or more specifically, what are the functions of nNOS isoforms in muscle? Using knockout mice, we study the impact of the loss of nNOSβ and nNOSμ on muscle. We have found that both nNOSβ and nNOSμ are necessary to maintain normal skeletal muscle size, strength and fatigue resistance. Our long term goal is to understand the underlying mechanisms responsible.  This has led to studies of nNOS isoform regulation of mitochondria, the “batteries” providing energy for the cell. We believe this work will lead to a better understanding of the molecular mechanisms governing exercise performance and may eventually provide mechanistic insights into why exercise is so good for you. 
2. How can you use a potentially highly diffusible free radical gas as a messenger?
We and others have identified three spatially and functionally distinct nNOS signaling compartments in skeletal muscle created by the differential targeting of nNOS splice forms (Figure 2).  nNOSμ is localized to the sarcolemma and cytosol and nNOSβ is localized the Golgi complex. Thus, we believe that tight control of nNOS localization and its targets facilitates the specific use of NO as a gaseous messenger. We are interested in understanding the mechanisms governing the localization of nNOS splice variants and their targets and how localization relates to function.
3. Can we just say “NO” to muscular dystrophy?
As stated above, we depend on strong healthy skeletal muscles for movement and breathing. This is exemplified by the disease Duchenne Muscular Dystrophy (DMD), where the loss of skeletal muscle mass and function leads to a loss of ambulation by the end of the first decade of life and respiratory failure in second or third decades of life.  DMD is caused by the loss of dystrophin which disrupts the tight spatial and regulatory controls on nitric oxide-cGMP signaling. We use the mdx mouse model of DMD to study the perturbation of nitric oxide-cGMP signaling and to test novel drug-based approaches to alleviate disease pathology. We have found that the use of sildenafil (Viagra®, Revatio®) to amplify NO-cGMP signals can prevent or even reverse skeletal and cardiac muscle dysfunction in the mdx mouse model of DMD. These findings led to Phase 2 clinical trials (NCT01168908) to test its efficacy in humans. We hope to build on our results with sildenafil and will be testing different approaches to amplify NO-cGMP signaling in mouse models of muscular dystrophy in the future.
A postdoctoral associate position is available to study nitric oxide signaling in the Percival lab.
The position involves the study of the metabolic functions of skeletal muscle neuronal nitric oxide synthase with special emphasis on the regulation of mitochondrial energetics in the context of obesity in novel mouse models. Highly motivated individuals with a Ph.D or M.D. with a strong interest in these areas and background in one or more of: molecular and cellular biology, muscle physiology, mitochondrial biology, animal models of disease or mouse transgenesis are encouraged to apply.

Applicants should email a statement of research interests, curriculum vitae, and the contact details of three references to: Dr Justin Percival,


Recent Publications
1. Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ. (2013) Mitochondrial targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 12:763-71.

2. Percival JM, Siegel MP, Knowles G, and Marcinek DJ. (2013) Defects in Mitochondrial Localization and ATP Synthesis in the mdx Mouse Model of Duchenne Muscular Dystrophy are Not Alleviated by PDE5 Inhibition. Human Molecular Genetics. 22(1):153-67.

3. Percival JM, Whitehead NP, Adams ME, Adamo CM, Beavo JA, Froehner SC. Sildenafil Reduces Respiratory Muscle Weakness and Fibrosis in the mdx Mouse Model of Duchenne Muscular Dystrophy.   J Pathol. 2012 May 31. doi: 10.1002/path.4054. [Epub ahead of print].

4. Percival JM. nNOS regulation of skeletal muscle fatigue and exercise performance. Biophysical Reviews. 2011 Volume 3(4):209-217.
5. Percival JM, Adamo CM, Beavo JA, Froehner SC. Evaluation of the therapeutic utility of phosphodiesterase 5A inhibition in the mdx mouse model of duchenne muscular dystrophy. Handb Exp Pharmacol. 2011;(204):323-44.

6. Adamo CM, Dai DF, Percival JM, Minami E, Willis MS, Patrucco E, Froehner SC, Beavo JA. Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2010;107(44):19079-83.

7. Percival JM, Anderson KN, Huang P, Adams ME, Froehner SC. Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. J Clin Invest. 2010;120(3):816-26.

8. Percival JM, Anderson KN, Gregorevic P, Chamberlain JS, Froehner SC. Functional deficits in nNOSmu-deficient skeletal muscle: myopathy in nNOS knockout mice. PLoS One. 2008;3(10):e3387.

9. Adams ME, Tesch Y, Percival JM, Albrecht DE, Conhaim JI, Anderson K, Froehner SC. Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed alpha-dystrobrevin. J Cell Sci. 2008;121(Pt 1):48-54.

10. Percival JM, Gregorevic P, Odom GL, Banks GB, Chamberlain JS, Froehner SC. rAAV6-microdystrophin rescues aberrant Golgi complex organization in mdx skeletal muscles. Traffic. 2007;8(10):1424-39.

12. Alessi A, Bragg AD, Percival JM, Yoo J, Albrecht DE, Froehner SC, Adams ME. gamma-Syntrophin scaffolding is spatially and functionally distinct from that of the alpha/beta syntrophins. Exp Cell Res. 2006;312(16):3084-95.



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