Research Background

Jeff joined the Kunkel Lab in 2013 after completing an undergraduate degree from State University of New York at Cortland, a master’s degree from the University of Massachusetts at Amherst, and a doctorate in Exercise Physiology at the Human Performance Laboratory at Ball State University. Jeff did post-doctoral training in muscle physiology in the Department of Biology at Marquette University with support from a NASA Postdoctoral Research Fellowship. His early work consisted of studying the detrimental effect of non-weight bearing actions on muscle function paired with the development of the exercise-based interventions. Within the Kunkel Lab, Jeff’s interest is focused on understanding how dystrophies and myopathies impact muscle contractility, looking at how contractile function can be improved or restored by novel therapeutic interventions. Jeff approaches his work across several levels of biological organization, from small zebrafish larvae to human muscle biopsies. By providing a physiological perspective with focus on muscle strength and performance, Jeff is able to translate functional assays that are typically performed on rodent muscles to the Kunkel lab zebrafish model.

Selected Publications

  1. Lambert MR, Spinazzola JM, Widrick JJ, Pakula A, Conner JR, Chin JE, Owens JM, Kunkel LM. PDE10A inhibition reduces the manifestation of pathology in DMD zebrafish and represses the genetic modifier PITPNA. Mol Ther 29: 1086–1101, 2021. View Abstract
  2. Tabebordbar M, Lagerborg KA, Stanton A, King EM, Ye S, Tellez L, Krunnfusz A, Tavakoli S, Widrick JJ, Messemer KA, Troiano EC, Moghadaszadeh B, Peacker BL, Leacock KA, Horwitz N, Beggs AH, Wagers AJ, Sabeti PC. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184: 4919–4938, 2021. View Abstract
  3. Hall A, Fontelonga T, Wright A, Bugda Gwilt K, Widrick J, Pasut A, Villa F, Miranti CK, Gibbs D, Jiang E, Meng H, Lawlor MW, Gussoni E. Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function. Skelet Muscle 10: 34, 2020. View Abstract
  4. Widrick JJ, Kawahara G, Alexander MS, Beggs AH, Kunkel LM. Discovery of novel therapeutics for muscular dystrophies using zebrafish phenotypic screens. J Neuromuscul Dis 6: 271–287, 2019. View Abstract

Publications

  1. High resolution kinematic approach for quantifying impaired mobility of dystrophic zebrafish larvae. bioRxiv. 2024 Dec 09. View Abstract
  2. DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism. FASEB J. 2023 10; 37(10):e23198. View Abstract
  3. Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset. Elife. 2023 07 11; 12. View Abstract
  4. Optimizing assays of zebrafish larvae swimming performance for drug discovery. Expert Opin Drug Discov. 2023 06; 18(6):629-641. View Abstract
  5. Electrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish. Sci Rep. 2023 05 03; 13(1):7191. View Abstract
  6. DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism. bioRxiv. 2023 Feb 27. View Abstract
  7. Dynamin-2 reduction rescues the skeletal myopathy of a SPEG-deficient mouse model. JCI Insight. 2022 08 08; 7(15). View Abstract
  8. miR-486 is essential for muscle function and suppresses a dystrophic transcriptome. Life Sci Alliance. 2022 09; 5(9). View Abstract
  9. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell. 2021 09 16; 184(19):4919-4938.e22. View Abstract
  10. Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function. Skelet Muscle. 2020 11 27; 10(1):34. View Abstract
  11. PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA. Mol Ther. 2021 03 03; 29(3):1086-1101. View Abstract
  12. The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice. Mol Ther. 2020 01 08; 28(1):189-201. View Abstract
  13. Passive force and viscoelastic properties of single fibers in human aging muscles. Eur J Appl Physiol. 2019 Oct; 119(10):2339-2348. View Abstract
  14. Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease. Sci Rep. 2019 08 06; 9(1):11392. View Abstract
  15. IMP2 Increases Mouse Skeletal Muscle Mass and Voluntary Activity by Enhancing Autocrine Insulin-Like Growth Factor 2 Production and Optimizing Muscle Metabolism. Mol Cell Biol. 2019 04 01; 39(7). View Abstract
  16. Transgenic zebrafish model of DUX4 misexpression reveals a developmental role in FSHD pathogenesis. Hum Mol Genet. 2019 01 15; 28(2):320-331. View Abstract
  17. Discovery of Novel Therapeutics for Muscular Dystrophies using Zebrafish Phenotypic Screens. J Neuromuscul Dis. 2019; 6(3):271-287. View Abstract
  18. A limb-girdle muscular dystrophy 2I model of muscular dystrophy identifies corrective drug compounds for dystroglycanopathies. JCI Insight. 2018 09 20; 3(18). View Abstract
  19. An open source microcontroller based flume for evaluating swimming performance of larval, juvenile, and adult zebrafish. PLoS One. 2018; 13(6):e0199712. View Abstract
  20. SPEG-deficient skeletal muscles exhibit abnormal triad and defective calcium handling. Hum Mol Genet. 2018 05 01; 27(9):1608-1617. View Abstract
  21. RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes. PLoS Genet. 2018 03; 14(3):e1007226. View Abstract
  22. Muscle dysfunction in a zebrafish model of Duchenne muscular dystrophy. Physiol Genomics. 2016 11 01; 48(11):850-860. View Abstract
  23. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 2016 Jan 22; 351(6271):407-411. View Abstract
  24. Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice. PLoS One. 2015; 10(10):e0140521. View Abstract
  25. Dystrophic muscle improvement in zebrafish via increased heme oxygenase signaling. Hum Mol Genet. 2015 Aug 01; 24(15):4480-1. View Abstract
  26. Gait characteristics of adults with Down syndrome explain their greater metabolic rate during walking. Gait Posture. 2015 Jan; 41(1):180-4. View Abstract
  27. Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. PLoS One. 2014; 9(9):e106590. View Abstract
  28. MicroRNA-486-dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy-associated symptoms. J Clin Invest. 2014 Jun; 124(6):2651-67. View Abstract
  29. Dystrophic muscle improvement in zebrafish via increased heme oxygenase signaling. Hum Mol Genet. 2014 Apr 01; 23(7):1869-78. View Abstract
  30. Concurrent muscle and bone deterioration in a murine model of cancer cachexia. Physiol Rep. 2013 Nov; 1(6):e00144. View Abstract
  31. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy. Hum Mol Genet. 2013 Apr 15; 22(8):1525-38. View Abstract
  32. Lack of neuromuscular origins of adaptation after a long-term stretching program. J Sport Rehabil. 2012 May; 21(2):99-106. View Abstract
  33. Lack of neuromuscular origins of adaptation after a long-term stretching program. J Sport Rehabil. 2012 May; 21(2):99-106. View Abstract
  34. An octaguanidine-morpholino oligo conjugate improves muscle function of mdx mice. Muscle Nerve. 2011 Oct; 44(4):563-70. View Abstract
  35. Aerobic capacity with hybrid FES rowing in spinal cord injury: comparison with arms-only exercise and preliminary findings with regular training. PM R. 2011 Sep; 3(9):817-24. View Abstract
  36. Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults. Age (Dordr). 2012 Feb; 34(1):215-26. View Abstract
  37. Calcium-activated force of human muscle fibers following a standardized eccentric contraction. Am J Physiol Cell Physiol. 2010 Dec; 299(6):C1409-17. View Abstract
  38. Intersession reliability of Hoffmann reflex gain and presynaptic inhibition in the human soleus muscle. Arch Phys Med Rehabil. 2009 Dec; 90(12):2131-4. View Abstract
  39. Combined effects of fatigue and eccentric damage on muscle power. J Appl Physiol (1985). 2009 Oct; 107(4):1156-64. View Abstract
  40. Economy and preferred speed of walking in adults with and without Down syndrome. Adapt Phys Activ Q. 2009 Apr; 26(2):118-30. View Abstract
  41. Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int. 2009 Sep; 20(9):1529-38. View Abstract
  42. Detrimental effects of reloading recovery on force, shortening velocity, and power of soleus muscles from hindlimb-unloaded rats. Am J Physiol Regul Integr Comp Physiol. 2008 Nov; 295(5):R1585-92. View Abstract
  43. Whole-body vibration slows the acquisition of fat in mature female rats. Int J Obes (Lond). 2008 Sep; 32(9):1348-54. View Abstract
  44. Relative effects of exercise training and alendronate treatment on skeletal muscle function of ovariectomized rats. Menopause. 2007 May-Jun; 14(3 Pt 1):528-34. View Abstract
  45. Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats. Bone. 2007 Aug; 41(2):290-6. View Abstract
  46. The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women. Bone. 2007 May; 40(5):1244-51. View Abstract
  47. Peak power of muscles injured by lengthening contractions. Muscle Nerve. 2006 Oct; 34(4):470-7. View Abstract
  48. Antioxidants did not prevent muscle damage in response to an ultramarathon run. Med Sci Sports Exerc. 2006 Jan; 38(1):72-80. View Abstract
  49. Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight. J Appl Physiol (1985). 2006 Mar; 100(3):951-7. View Abstract
  50. Effect of hindlimb suspension on the functional properties of slow and fast soleus fibers from three strains of mice. J Appl Physiol (1985). 2003 Dec; 95(6):2425-33. View Abstract
  51. Functional adaptability of muscle fibers to long-term resistance exercise. Med Sci Sports Exerc. 2003 Jun; 35(6):944-51. View Abstract
  52. Cross-bridge mechanisms of muscle weakness in multiple sclerosis. Muscle Nerve. 2003 Apr; 27(4):456-64. View Abstract
  53. Morphological and functional characteristics of skeletal muscle fibers from hormone-replaced and nonreplaced postmenopausal women. J Gerontol A Biol Sci Med Sci. 2003 Jan; 58(1):3-10. View Abstract
  54. Spinal reflex profiles in early postmenopausal women. J Gend Specif Med. 2003; 6(3):27-9. View Abstract
  55. Functional properties of human muscle fibers after short-term resistance exercise training. Am J Physiol Regul Integr Comp Physiol. 2002 Aug; 283(2):R408-16. View Abstract
  56. Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function. J Appl Physiol (1985). 2002 Jul; 93(1):354-60. View Abstract
  57. Effect of P(i) on unloaded shortening velocity of slow and fast mammalian muscle fibers. Am J Physiol Cell Physiol. 2002 Apr; 282(4):C647-53. View Abstract
  58. Thin filament diversity and physiological properties of fast and slow fiber types in astronaut leg muscles. J Appl Physiol (1985). 2002 Feb; 92(2):817-25. View Abstract
  59. Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol. 2001 Sep; 204(Pt 18):3201-8. View Abstract
  60. Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. J Appl Physiol (1985). 2001 Jul; 91(1):57-64. View Abstract
  61. Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight. J Appl Physiol (1985). 2001 Jun; 90(6):2203-11. View Abstract
  62. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey. Am J Physiol Regul Integr Comp Physiol. 2000 Nov; 279(5):R1546-57. View Abstract
  63. Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol (1985). 2000 Aug; 89(2):823-39. View Abstract
  64. Decreased thin filament density and length in human atrophic soleus muscle fibers after spaceflight. J Appl Physiol (1985). 2000 Feb; 88(2):567-72. View Abstract
  65. Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys. J Gravit Physiol. 2000 Jan; 7(1):S37-8. View Abstract
  66. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey. J Gravit Physiol. 2000 Jan; 7(1):S53-4. View Abstract
  67. Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J Physiol. 1999 May 01; 516 ( Pt 3):915-30. View Abstract
  68. Substrate and enzyme profile of fast and slow skeletal muscle fibers in rhesus monkeys. J Appl Physiol (1985). 1999 Jan; 86(1):335-40. View Abstract
  69. Force-velocity-power and force-pCa relationships of human soleus fibers after 17 days of bed rest. J Appl Physiol (1985). 1998 Nov; 85(5):1949-56. View Abstract
  70. Disproportionate loss of thin filaments in human soleus muscle after 17-day bed rest. Muscle Nerve. 1998 Oct; 21(10):1280-9. View Abstract
  71. Velocity, force, power, and Ca2+ sensitivity of fast and slow monkey skeletal muscle fibers. J Appl Physiol (1985). 1998 May; 84(5):1776-87. View Abstract
  72. Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers. Am J Physiol. 1997 Nov; 273(5 Pt 1):C1690-9. View Abstract
  73. Effect of intermittent weight bearing on soleus fiber force-velocity-power and force-pCa relationships. J Appl Physiol (1985). 1997 Jun; 82(6):1905-10. View Abstract
  74. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J Appl Physiol (1985). 1997 Jan; 82(1):189-95. View Abstract
  75. Contractile properties of rat, rhesus monkey, and human type I muscle fibers. Am J Physiol. 1997 Jan; 272(1 Pt 2):R34-42. View Abstract
  76. Isometric force and maximal shortening velocity of single muscle fibers from elite master runners. Am J Physiol. 1996 Aug; 271(2 Pt 1):C666-75. View Abstract
  77. Force-velocity and force-power properties of single muscle fibers from elite master runners and sedentary men. Am J Physiol. 1996 Aug; 271(2 Pt 1):C676-83. View Abstract
  78. Soleus fiber force and maximal shortening velocity after non-weight bearing with intermittent activity. J Appl Physiol (1985). 1996 Mar; 80(3):981-7. View Abstract
  79. Muscle mechanics: adaptations with exercise-training. Exerc Sport Sci Rev. 1996; 24:427-73. View Abstract
  80. Dry-land resistance training for competitive swimming. Med Sci Sports Exerc. 1993 Aug; 25(8):952-9. View Abstract
  81. Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration. J Appl Physiol (1985). 1993 Jun; 74(6):2998-3005. View Abstract
  82. Time of day effects on sympathoadrenal and pressor reactivity to exercise in healthy men. Eur J Appl Physiol Occup Physiol. 1993; 67(2):159-63. View Abstract
  83. Reduced training volume and intensity maintain aerobic capacity but not performance in distance runners. Int J Sports Med. 1993 Jan; 14(1):33-7. View Abstract
  84. Day to day variation in time trial cycling performance. Int J Sports Med. 1992 Aug; 13(6):467-70. View Abstract
  85. Time course of glycogen accumulation after eccentric exercise. J Appl Physiol (1985). 1992 May; 72(5):1999-2004. View Abstract
  86. Reliability of the serial sampling technique for determination of gastric emptying. Int J Sports Med. 1992 Apr; 13(3):216-8. View Abstract
  87. Effect of internal work on the calculation of optimal pedaling rates. Med Sci Sports Exerc. 1992 Mar; 24(3):376-82. View Abstract
  88. Treadmill validation of an over-ground walking test to predict peak oxygen consumption. Eur J Appl Physiol Occup Physiol. 1992; 64(4):304-8. View Abstract
  89. Development of a single-stage submaximal treadmill walking test. Med Sci Sports Exerc. 1991 Aug; 23(8):966-73. View Abstract
  90. Effects of drink carbonation on the gastric emptying characteristics of water and flavored water. Int J Sport Nutr. 1991 Mar; 1(1):45-51. View Abstract

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