Ronald Gerald Haller

Professor of Neurology and Internal Medicine

DEGREE

Stanford University

B.A. 

1964

University of Washington

M.D.

1969

A.P. Giannini Foundation Scholarship, BA with distinction, Honors in Humanities, Stanford University; Alpha Omega Alpha, University of Washington School of Medicine; American Neurological Association (active); Scientific Advisory Committee, Muscular Dystrophy Association, USA; Mary Quincy Parsons and Kelsey Louise Wright Professor in Mitochondrial Disease Research

1. Haller RG, Lockard JS, Foltz EL, Avoidance behavior and ilium motility post-cingulumectomy in monkey. Biol Psych 11:175-193, 1976.
2. Lockard JS, Foltz EL, Ehle AL, Haller RG, Ilium motility during avoidance conditioning in monkey pre- and post-cingulumectomy. Physiol Behav 18:111-117, 1977.
3. Knochel JP, Barsenas CG, Fuller TJ, Haller RG, Carter NW, Hypophosphatemia and rhabdomyolysis. J Clin Invest 62:1240-1246, 1978.
4. Haller RG, Drachman DB, Alcoholic rhabdomyolysis: an experimental model in the rat. Science 208:412-415, 1980.
5. Anderson R, Cohen M, Haller RG, Elms J, Carter NW, Knochel JP, Skeletal muscle phosphorus and magnesium deficiency in alcoholic myopathy. Mineral and Elect Metab 4:106-112, 1980.
6. Long CS, Haller RG, Foster DW, McGarry JD, Kinetics of carnitine-dependent fatty acid oxidation: implications for human carnitine deficiency. Neurology 32:663-666, 1982.
7. Haller RG, Dempsey WB, Feit H, Cook JD, Knochel JP, Low muscle pyridoxine in McArdle’s syndrome. Am J Med 74:217-220, 1983.
8. Haller RG, Lewis SF, Cook JD, Blomqvist CG, Hyperkinetic circulation during exercise in neuromuscular disease. Neurology 33:1283-1287, 1983.
9. Haller RG, Carter NW, Ferguson E, Knochel JP, Serum and muscle potassium in experimental alcoholic myopathy. Neurology 34:529-532, 1984.
10. Lewis SF, Haller RG, Cook JD, Blomqvist CG, Neuromuscular diseases as models of cardiovascular regulation during exercise. Med Sci Sports and Exercise 16:466-471, 1984.
11. Haller RG, Lewis SF, Pathophysiology of exercise performance in muscle disease. Med Sci Sports and Exercise 16:456-459, 1984.
12. Lewis SF, Haller RG, Cook JD, Blomqvist CG, Metabolic control of the cardiac output response to exercise in McArdle’s disease. J Appl Physiol 57:1749-1753, 1984.
13. Haller RG, Lewis SF, Cook JD, Blomqvist CG, Myophosphorylase deficiency impairs muscle oxidative metabolism. Ann Neurol 17:196-199, 1985.
14. Haller RG, Experimental acute alcoholic myopathy: A histochemical study. Muscle & Nerve 8:246-263, 1985.
15. Lewis SF, Haller RG, Cook JD, Nunnally RL. Muscle fatigue in McArdle’s disease studied by 31-P NMR: effect of glucose infusion. J Appl Physiol 59: 1991-1994, 1985.
16. Lewis SF, Haller RG. The pathophysiology of McArdle’s disease: clues to regulation in exercise and fatigue. J Appl Physiol 61:391-401, 1986.
17. Haller RG, Lewis SF. Abnormal ventilation during exercise in McArdle’s disease: modulation by substrate availability. Neurology 36:716-719, 1986.
18. Fleckenstein JL, Peshock RM, Lewis SF, Haller RG. Focal muscle injury and atrophy in human muscle glycolytic disorders. Muscle & Nerve 12:849-855, 1989.
19. Haller RG, Lewis SF, Estabrook RW, Servidei S, DiMauro S, Foster DW, Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency. J Clin Invest, 84:155-161, 1989.
20. Pryor SL, Lewis SF, Haller RG, Bertocci LA, Victor RG, Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle’s disease). J Clin Invest, 85:1444-1449, 1990.
21. Sahlin K, Areskog N-H, Haller RG, Henriksson KG, Jorfeldt L, Lewis SF. Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle’s disease. J Appl Physiol 69:1231-1235, 1990.
22. Haller RG and Lewis SF. Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency. N Engl J Med 324:364-369, 1991.
23. Bertocci LA, Haller RG, Lewis SF, Fleckenstein JL, Nunnally, RL. Altered high energy phosphate metabolism during exercise in muscle phosphofructokinase deficiency. J Appl Physiol 70:1201-1207, 1991.
24. Lewis SF, Vora S., Haller RG. Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency. J Appl Physiol 70:391-398, 1991.
25. Fleckenstein JL, Haller RG, Lewis SF, Bertocci LA, Payne J, Barker B, Archer B, Peshock RM. Myophosphorylase deficiency impairs exercise-enhancement on MRI of skeletal muscle. J Appl Physiol 71:961-969, 1991.
26. Katz A, Spencer MK, Lillioja S, Yan Z, Mott DM, Haller RG, Lewis SF. Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase-1. Am J Physiol 261 (Endocrinol. Metab. 24):E473-E478, 1991.
27. Haller RG, Henriksson KG, Jorfeldt L, Hultman E, Wibom R, Sahlin K, Areskog N-H, Gunder M, Ayyad K, Blomqvist CG, Hall RE, Thuillier P, Kennaway NG, Lewis SF. Deficiency of muscle succinate dehydrogenase and aconitase: pathophysiology of exercise in a novel human muscle oxidative defect. J Clin Invest 88:1197-1206, 1991.
28. Vissing J, Lewis SF, Galbo H, Haller RG. Effect of deficient muscular glycogenolysis on extramuscular fuel production in exercise. J Appl Physiol 72:1773-1779, 1992.
29. Archer BT, Fleckenstein JL, Bertocci LA, Haller RG, Barker B, Parkey RW, Peshock RM. Effect of perfusion on exercised muscle: MRI evaluation. J Magnetic Resonanace Imaging 2:407-413, 1992.
30. Metzler JP, Fleckenstein JL, White CL III, Haller RG, Frenkel G, Greenlee R. MRI evaluation of amyloid myopathy. Skeletal Radiology 21:463-465, 1992.
31. Bertocci LA, Haller RG, Lewis SF. Muscle metabolism during lactate infusion in muscle phosphofructokinase deficiency. J Appl Physiol 74(3):1342-1347 1993.
32. Pitt AM, Fleckenstein JL, Greenlee RG Jr., Burns DK, Bryan WW, Haller RG. MRI-guided biopsy in inflammatory myopathy: initial results. Magnetic Res Imaging 11:1093-1099, 1993.
33. Hall RE, Henriksson KG, Lewis SF, Haller RG, Kennaway NG. Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency: abnormalities of several iron-sulfur proteins. J Clin Invest 92:2660-2666, 1993.
34. Tsujino S, Shanske S, Brownell AKW, Haller RG, DiMauro S. Molecular genetic studies of muscle lactate dehydrogenase deficiency in white patients. Ann Neurol 36:661-664, 1994.
35. Fleckenstein JL, Watumull D, Bertocci LA, Nurenberg P, Peshock RM, Payne JA, Haller RG. Muscle recruitment variations during wrist flexion exercise: MRI evaluation. Journal of Computer Assisted Tomography 18:449-53, 1994.
36. Haller RG, Oxygen utilization and delivery in metabolic myopathies.  Ann Neurol 36:811-813, 1994.
37. Sahlin K, Henriksson KG, Jorfeldt L, Lewis SF, Haller RG. Tricarboxylic acid cycle intermediates during incremental exercise in healthy subjects and in patients with McArdle’s disease. Clinical Science 88:687-693, 1995.
38. Vissing J, Galbo H, Haller RG. Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis due to muscle phosphofructokinase deficiency. Neurology 47:766-771, 1996.
39. Vissing J, Galbo H, Haller RG. Exercise fuel mobilization in mitochondrial myopathy: a metabolic dilemma. Ann Neurol.40: 655-662, 1996.
40. Sobreira C, Hirano M, Shanske S, Keller K, Haller RG, Davidson E, Santorelli FM, Miranda AF, Bonilla E, Mojon DS, Barreira AA, King MP, DiMauro S. Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. Neurology 48:1238-1243, 1997.
41. Haller RG, Clausen T, Vissing J. Reduced levels of skeletal muscle Na+K+ - ATPase in McArdle Disease. Neurology 50:37-40, 1998.
42. Vissing J, Vissing SF, MacLean DA, Saltin B, Quistorff B, Haller RG. Sympathetic activation in exercise is not dependent on muscle acidosis: direct evidence from studies in metabolic myopathies. J Clin Invest. 101:1654-1660, 1998.
43. Evans GFF, Haller RG, Wyrick PS, Parkey RW, Fleckenstein JL. Delayed onset muscle soreness after submaximal exercise: correlations between MRI and clinical measures. Radiology 208: 815-820, 1998.
44. MacLean D. Vissing J, Vissing S, Haller RG. Oral branched chain amino acids do not improve exercise capacity in McArdle disease. Neurology.51:1456-1459, 1998.
45. Vissing J, Schmalbruch H, Haller RG, Clausen T. Muscle phosphoglycerate mutase deficiency with tubular aggregates: treatment with dantrolene. Ann Neurol 46:274-77, 1999.
46. Haller RG.  Treatment of McArdle's disease.  Arch Neurol 57:923-924, 2000.
47. Wariar R., Gaffke JN, Haller RG, Bertocci LA. A modular system for clinical measurement of impaired skeletal muscle oxygenation. J Appl Physiol, 88:315-25, 2000.
48. Wolfe GI, Baker NS, Haller RG, Burns DK, and Barohn RJ. McArdle’s disease presenting with asymmetric, late-onset arm weakness. Muscle & Nerve ;23(4):641-645, 2000.
49. Karadimas CL, Greenstein P, Sue CM, Joseph JT, Tanji K, Haller RG, Taivassalo T, Davidson MM, Shanske S, Bonilla E, DiMauro S. Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mtDNA. Neurology 55:644-649, 2000.
50. Taivassalo T, Shoubridge E, Eng JCM, Kennaway N, DiMauro S, Arnold DL, Haller RG. Aerobic conditioning in mitochondrial myopathies: physiological, biochemical and genetic effects. Ann Neurol 50:133-141, 2001.
51. Vissing J, MacLean DA, Vissing SF, Sander, M, Saltin B, Haller RG. The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in McArdle’s disease. J Physiol 537.2:641-49, 2001.
52. Taivassalo T, Abbott A, Wyrick P, Haller RG. Venous pO₂ during aerobic forearm exercise: an index of impaired oxidative metabolism in mitochondrial myopathy. Ann Neurol 51:38-44, 2002.
53. Nielsen JN, Vissing J, Wojtaszewski JFP, Haller RG, Begum N, Richter EA. Decreased insulin action in skeletal muscle from patients with McArdle’s disease. Am J Physiol., 282:E1267-75, 2002.
54. Nielsen JN, Wojtaszewski JFP, Haller RG, Grahame-Hardie D, Kemp B, Richter EA, Vissing J. Role of 5’-AMP activated protein kinase in glycogen synthase activity and glucose utilization:  insights from patients with McArdle’s disease. J Phyiol, 541 (Pt 3):979-89 2002.
55. Haller RG and Vissing J. The spontaneous "second wind" and a glucose-induced  "second wind" in McArdle disease - oxidative mechanisms, Arch Neurol,59:1395-1402, 2002.
56. Kazemi-Esfarjani P, Skomorowska E, Dysgaard Jensen T, Haller RG, Vissing J. A Non-ischemic Forearm Exercise Test for McArdle Disease. Annals of Neurology, 52(2):153-159, 2002.
57. Taivassalo T, Dysgaard Jensen T, Kennaway N, DiMauro S, Vissing J, Haller RG. The spectrum of exercise capacity in mitochondrial myopathies: a study of 40 patients. Brain, 126:413-423, 2003.
58. Walton ME, Ebert DJW, Haller RG. Relative rates of anaplerotic flux in rested and contracted rat skeletal muscle measured by 13C NMR spectroscopy. J Physiol 548:541-548, 2003.
59. Ebert D, Haller RG, Walton ME Energy contribution of octanoate to intact rat brain metabolism measured by 13C Nuclear Magnetic Resonance Spectroscopy. J Neurosci 23(13):5928-5935, 2003.
60. Vissing J and Haller RG. A diagnostic cycle test in McArdle disease. Ann Neurol., 54:539-42, 2003.
61. Walton ME, Ebert DJW and Haller RG. Octanoate oxidation measured by 13C NMR spectroscopy in rat skeletal muscle, heart and liver. J Appl Physiol 95(5):1908-16, 2003.
62. Vissing J and Haller RG. The effect of oral sucrose on exercise tolerance in McArdle's disease, N Eng J Med, 349:2503-9, 2003.
63. Haller RG and Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology, 62:82-87, 2004.
64. Taivassalo T and Haller RG. Implications of Exercise Training in Mitochondrial DNA defects: Use it or lose it? Biochim Biophys Acta.- Bioenergetics 1659:221-31, 2004.
65. Haller RG and Vissing J. Functional evaluation of metabolic myopathes. In: Myology, ed by A.G. Engel and C. Franzini-Armstrong, McGraw-Hill, New York. (3nd edition) pp 665-679, 2004.
66. Vissing J, Quistorff B, Haller RG. Effects of fuels on exercise capacity in muscle phosphoglycerate mutase deficiency. Arch Neurol, 62:1352-6, 2005.
67. Haller RG, Wyrick P, Taivassalo, T, Vissing J. Aerobic Conditioning: an effective therapy in McArdle Disease. Ann Neurol. 59:922-8, 2006.
68. Taivassalo T, Gardiner JL, Taylor RW, Schaefer AM, Newman J, Barron MJ, Haller RG, Turnbull DM. Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain, 129:3391-3401, 2006.
69. Oktay, Y, Dioum E, Marsuzaki S, Ding K, Yan L-J, Haller RG, Szweda LI, Garcia JA. HIF-2a null liver mitochondria have reduced frataxin levels and impaired mitochondrial aconitase activity. J Biol Chem, 282:11750-6, 2007.
70. Adhihetty P, Taivassalo T, Haller RG, Walkinshaw D, Hood D. The effect of training on the expression of mitochondrial biogenesis- and apoptosis- related proteins in skeletal muscle of patients with mtDNA defects. Am J Physiol: Endocrinology and Metabolism, 293(3):E672-80, 2007.
71. Mochel F, Kinght MA, Tong W-H, Hernandez D, Ayyad K, Taivassalo T, Andersen P, Singelton A, Rouault TA, Fischbeck KH, Haller RG. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. AM J
    Hum Genetics, 82:652-60, 2008.
72. Son M, Leary SC, Romain N, Pierrel F, Winge DR, Haller RG, Elliott JL. Isolated cytochrome c oxidase (COX) deficiency in G93A SOD1 mice over-expressing CCS protein. J Biol Chem, 283(18): 12267-75 2008.
73. Swalwell H, Blakely EL, Suttton R, Tonska K, Elstner M, He L, Taivassalo T, Burns DK, Turnbull DM, Haller RG, Davidson MM, Taylor RW. A homoplasmic mitochondrial DNA variant (m.7472A.C) can influence the phenotype of the pathogenic m7472Cins MTTS1 mutation: are two mutations better than one? Eur J Hum Genet, 16:1265-74, 2008].
74. Andersen ST, Haller RG, Vissing J. Oral sucrose shortly before exercise improves work capacity in McArdle disease. Arch Neurol, 65:786-9, 2008.
75. Murphy JL, Blakely EL. Schaefer AM, He L, Wyrick P, Haller RG, Taylor RW, Turnbull DM, Taivassalo T. Resistance training in patients with single, large scale deletions of mitochondrial DNA. Brain, 131:2832-40, 2008.

Grant Support:

Ongoing Research Support

1. R01 AR050597

   Haller (PI)

   10/01/2006 - 9/30/2011

   "Exercise Adaptations in mitochondrial myopathy"

   This a study of the long term effects of exercise training and detraining upon muscle function, oxidative capacity, quality of life and distribution of mutant vs. wild type mtDNA in patients with heteroplasmic mitochondrial DNA mutations associated with exertional fatigue and weakness.

   Role: (PI)

    

2. Grant # NNH047ZUU003N     

   Levine (PI)

   6/1/2005 – 5/31/2009                                                  

   NASA- NSBRI

   “The Multisystem Effect of Exercise Training/Nutritional Support During Prolonged Bed Rest Deconditioning:  An Integrative Approach to Countermeasure Development for the Heart, Lungs, Muscles and Bones”

   The global objective of this proposal is to test an integrated countermeasure that will be effective against cardiovascular deconditioning, skeletal muscle atrophy, and bone demineralization, and that ultimately can be applied practically aboard the International Space Station or a mission to Mars.

   Role:  Co-Investigator

    

3. Grant # NA    

   Haller (PI)

   5/15/2008 – 5/14/2009                                                  

   National Organization of Rare Diseases - Kearns Sayre Proposal

   “Mitochondrial Aconitase: A Measure of Oxidative Stress in Kearns Sayre Syndrome"

   The objective of this study is to provide is to provide preliminary data relative for the hypothesis that mitochondrial myopathy due to heteroplasmic single large scale deletions are associated with a greater level of oxidative stress in comparison with patients with mtDNA point mutations levels as a potential ratonale for antioxidant therapy.

   Role:  PI

    

4. Grant # NA    

   Haller (PI)

   11/10/2008 – 3/10/2010                                                  

   CHDI Foundation

   “Mitochondrial Stress Test Validation Study in Subjects with Huntington's Disease"

   To determine the ability of exercise testing to identify evidence of impaired skeletal muscle oxidative metabolism co with a defect in mitochondrial oxidative phosphorylation in patients with Huntington's Disease.

   Role:  PI

Completed Research Support

1)   Grant # 02-10 

Taivassalo (PI) 

7/01/2002 – 6/30/2004

 UMDF     

"Exercise-induced mitochondrial gene shifting: resistance training as therapy for sporadic mtDNA mutations"     

The purpose of this grant is to perform work to determine the efficacy of a novel approach to therapy for selective patients with mitochondrial disorders based on the concept of mitochondrial gene shifting.                                 

Role: Co-Investigator

2)  Grant #3498 

Taivassalo (PI) 

1/01/2003 – 12/31/2005

MDA     

"Exercise Training as Therapy for Mitochondrial Myopathies" 

The purpose of this grant is to perform work to determine the safety and efficacy of endurance and resistance exercise training in the treatment of patients with mitochondrial myopathies associated with pathogenic mutations of mitochondrial or nuclear DNA, who endure disabling fatigability and weakness.                                             

Role: Co-Investigator

3) No Grant # assigned 

Haller (PI) 

1/1/1998 - 12/31/2001 (renewal 1/1/01 - 12/31/2003)

Muscular Dystrophy Association 

"Evaluation and Treatment of Metabolic Myopathies" 

The major goal of this project is to evaluate causes and treatments of rhabdomyolysis.

Role:  PI 

4) Grant # NA

Haller (PI)

10/1/1999 - 9/30/2004(renewal 10/01/2004- 9/30/2008)

VA Merit Review

"Muscle Glycolytic Enzyme Deficiency - Metabolic and Physiologic Effects"

The objective of this study is to advance understanding of the pathophysiology of neurological/neuromuscular disorders associated with inborn errors of carbohydrate metabolism. The focus of the study is to understand the mechanism, clinical consequences, and possible treatment of the limitation in muscle oxidative metabolism that results from severe limitations of glycogenolysis or glycolysis.

Role:  PI

 

5) Grant # MDA3728

Haller (PI)

01/01/2004 - 12/31/2006

Muscular Dystrophy Association

"Exercise Therapy for Mitochondrial Myopathy"

The purpose of this grant is perform work to determine the safety and efficacy of endurance and resistance exercise training in the treatment of patients with mitochondrial myopathies associated with pathogenic mutations of mitochondrial or nuclear DNA, who endure disabling fatigability and weakness.

Role:  PI