Robert W. Grange, MS, PhD

Program Focus

I have been conducting skeletal muscle function assays for over 30 years. My approaches to these studies have included assessment of actin-myosin interactions in single fibers, contractile and mechanical properties in dystrophic mouse skeletal muscle in vitro, including from pups as young as P1, and in dystrophic GRMD and XLMTM dog muscles in vivo.

In addition, I have determined the functional outcomes of various treatments to rescue dystrophic and XLMTM skeletal muscle. In mice, these treatments have included both dietary (e.g., green tea extract) and genetic approaches (e.g., microdystrophin; embryonic stem cells), and in dogs and mice, gene transfer. We recently published a long-term study (52 week; Hamm et al., 2023) that documented over-time, improvements in the in vivo functional contractile and endurance  characteristics of mdx mice treated with microdystrophin ± nNOS binding site, with and without voluntary running wheel exercise.

This long-term study was a follow-up to a similar but short-term study  (Hamm et al., 2021) both completed by my research team. We have also employed transcriptome analysis to explore and define adaptive mechanisms in diseased skeletal muscle treated with gene transfer (Dupont et al., 2020; Hamm et al.,  2021). We are continuing to conduct detailed analyses of the transcriptome and proteome to identify the adaptive mechanisms responsible for the improved contractile and bioenergetic function of the microdystrophin-treated mdx mice, and the complementary effects of running wheel exercise.

Dr. Grange’s NCBI (PubMed) bibliography can be viewed here.

Dr. Grange’s Google Scholar bibliography can be viewed here.

Reviewed Journals

• Hamm SE,  Yuan C, McQueen LF, Wallace MA, Zhang H, Arora A, Garofalo AM,  McMillan RP, Lawlor MW, Prom MJ, Ott EM, Yan J, Addington AK, Morris CA, Gonzalez JP, and Grange RW. Prolonged voluntary wheel running reveals unique adaptations in mdx mice treated with microdystrophin constructs ± the nNOS-binding site. 2023. Front Physiol.14:1166206. doi: 10.3389/fphys.2023.
• Knott B, Kocher MA, Paz HA, Hamm SE, Fink W, Mason J, Grange RW, Wankhade UD, Good DJ. Dietary Conjugated Linoleic Acid Reduces Body Weight and Fat in Snord116m+/p- and Snord116m-/p- Mouse Models of Prader-Willi Syndrome. 2022. Nutrients14(4):860. doi: 10.3390/nu14040860.
• Hamm SE, Fathalikhani DD, Bukovec KE, Addington AA, Zhang H, Perry JB, McMillan RP, Lawlor MW, Prom MJ, Vanden Avond MA, Kumar SN, Coleman KE, Dupont JB, Mack DL, Brown DA, Morris CA, Gonzalez JP,  and Grange RW. 2021. Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice. Mol Ther Methods Clin Dev 21:144-160. doi: 10.1016/j.omtm.2021.02.024.
• Rezvani SN, Nichols AEC, Grange RW, Dahlgren LA, Brolinson PG, and Wang VM. 2021. A novel murine muscle loading model to investigate Achilles musculotendinous adaptation. J Appl Physiol 130(4):1043-1051. doi: 10.1152/japplphysiol.00638.2020.
• Yuan C, Arora A, Garofalo AM, and  Grange RW. 2021. Potential cross-talk between muscle and tendon in Duchenne muscular dystrophy. Connect Tissue Res 62(1):40-52. doi: 10.1080/03008207.2020.1810247.
• Bukovec KE, Xiao Hu X, Borkowski M, Jeffery D, Blemker SS, and Grange RW. 2020. A novel ex vivo protocol to mimic human walking gait: implications for Duchenne muscular dystrophy. J Appl Physiol 129(4):779-791. doi: 10.1152/japplphysiol.00002.
• Barraza-Flores P, Bukovec KE, Dagda M, Conner BW, Oliveira-Santos A, Grange RW, Burkin DJ. 2020. Laminin-111 protein therapy after disease onset slows muscle disease in a mouse model of Laminin-α2 related congenital muscular dystrophy. Hum Mol Genet 29(13):2162-2170. doi: 10.1093/hmg/ddaa104.
• Good DJ, Zhang H, Grange RW, and Braun T. 2020. POMC Neurons and the Transcriptional Regulation of Motivated Exercise. Response to initial review completed; returned for final review.   Exerc Sport Sci Rev. 48(2): 74-82. doi: 10.1249/JES.0000000000000219.
• Dupont JB, Guo J, Renaud-Gabardos E, Poulard K, Latournerie V, Lawlor MW, Grange RW, Gray JT, Buj-Bello A, Childers MK, Mack DL. 2019. AAV-Mediated Gene Transfer Restores a Normal Muscle Transcriptome in a Canine Model of X-Linked Myotubular Myopathy. Mol Ther 28(2):382-393. doi: 10.1016/j.ymthe.2019.10.018.
• Mack DL, Poulard K, Goddard MA, Latournerie V, Snyder JM, Grange RW, Elverman MR, Denard J, Veron P, Buscara L, Le Bec C, Hogrel JY, Brezovec AG, Meng H, Yang L, Liu F, O’Callaghan M, Gopal N, Kelly VE, Smith BK, Strande JL, Mavilio F, Beggs AH, Mingozzi F, Lawlor MW, Buj-Bello A, and Childers MK.. 2017. Systemic AAV8-mediated gene therapy drives whole-body correction of myotubular myopathy in dogs. Mol Ther. 25(4):839-854.

Oral Presentations

• November 2022. Endurance exercise complements microdystrophin gene treatment.  Presentation in symposium entitled, Duchenne Muscular Dystrophy: What Can Exercise Offer? Canadian Society for Exercise Physiology. Fredericton, New Brunswick, Canada.
• October 2022. Effects of exercise on microdystrophin gene therapy in mdx mice. Department of Physiology and Pharmacology College of Veterinary Medicine, University of Georgia.
• May 2022. Effects of exercise on microdystrophin gene therapy in mdx mice. University of Maryland School of MedicineT32 Interdisciplinary Program in Muscle Biology virtual seminar series. Baltimore, Maryland.

Poster Presentations

• Brisendine M, Ninchenko A, Bandara A, Specht K, Bond J, Addington A, Craige S, Grange R, and Drake JC. Aerobic exercise training does not improve skeletal muscle mitochondrial respiration in a mouse model of Alzheimer’s Disease. Advances in Skeletal Muscle Biology in Health and Disease, University of Florida, Mar 15-17, 2023.
• Hamm S*^†, Fathalikhani DD*^†, Bukovec KE*^†, McQueen LF*, Wallace MA*, Yuan C*, Zhang H***, Arora A***, Garofalo AM**, Garrison V**, Nolan DC**, Lawlor MW*, Prom MJ, Beatka M, Ott E, Addington AK, McMillan RP, Morris CA, Gonzalez JP, and Grange RW.  Improved mdx muscle function is sustained after microdystrophin gene therapy combined with voluntary running for 52 weeks. Frontiers in Myogenesis, Herradura, Costa Rica, November 15-19, 2021.
• McQueen LF*, Hamm SE*, Yuan C*, Dupont JB, Mack DL, and Grange RW. Potential adaptive signaling pathways in mdx mice treated with micro-dystrophin combined with voluntary running. Frontiers in Myogenesis, Herradura, Costa Rica, November 15-19, 2021.
• Bukovec KE^a, Grange RW. History of eccentric contractions in Duchenne Muscular Dystrophy. Boehringer Ingelheim Veterinary Scholars-NIH National Veterinary Scholars Symposium, Virtual, August 4-6, 2021. ^aKate Bukovec is one of my former M.S. students. I mentored her in the 2021 Summer Veterinary Student Research Program.
• Baddour T, Rezvani SN, Grange RW, Dahlgren LA, Brolinson PG, Arena SL, and Wang VM. Hill-Type Muscle-Tendon Modeling of Plantar Flexion in the Mouse Hindlimb. Orthopedic Research Society (ORS) Annual Meeting, February 12-16, 2021 (Virtual).
• Grange RW, Chin ER, Klaiman J, Hwee DT, Kim LH, Morgan BP, Malik FI, Childers MK, Luo S, and Mack DL. A Canine Model for Understanding the Pharmacokinetic/Pharmacodynamic Relationship of Muscle-targeted Therapies. World Muscle Society Congress (Virtual) September 28 – October 2, 2020.
• Rezvani SN, Grange RW, Dahlgren LA, Brolinson PG, Wang VM.  Eccentric muscle loading improved tendon biomechanical properties in a murine model of Achilles tendinopathy. Orthopedic Research Society (ORS) Annual Meeting, Phoenix, Arizona, February 8-11, 2020.
• Hamm SE^†*, Fathalikhani DD^†*, Bukovec KE^†*, Addington AK, Zhang H, Perry JB, Mansueto A, McMillan RP, Lawlor MW, Coleman K, Mack DL, Dupont JB, Brown DA, Morris CA, Gonzalez JP, and Grange RW. Effects of exercise on the efficacy of microdystrophin gene therapy.  Canadian Society of Exercise Physiology, Kelowna, BC, Canada, November 6-9, 2019.
• Hamm SE^†*, Fathalikhani DD^†*, Bukovec KE^†*, Addington AK, Zhang H, Perry JB, Mansueto A, McMillan RP, Lawlor MW, Coleman K, Mack D, JB, Brown DA, Morris CA, Gonzalez JP, and Grange RW. Effects of exercise on the efficacy of microdystrophin gene therapy.  European Society of Gene and Cell Therapy, Barcelona, Spain, October 22-25, 2019.
• Hamm SE^†*, Fathalikhani DD^†*, Bukovec KE^†*, Addington AK, Zhang H, Perry JB, Mansueto A, McMillan RP, Lawlor MW, Coleman K, Brown DA, Morris CA, Gonzalez JP, and Grange RW. Effects of exercise on the efficacy of microdystrophin gene therapy.  Frontiers in Myogenesis, San Jose, Costa Rica, September 23-27, 2019.