OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)
NAME: Ricardo A. Maselli
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
FIELD OF STUDY
University of Buenos Aires, Buenos Aires,
A. Personal Statement
My research interests focus on understanding the pathogenesis of human Congenital Myasthenic Syndromes (CMS), which are a group of inherited disorders of neuromuscular transmission characterized by marked genotypic and phenotypic variability. My research endeavors initially concentrated in the study of the function and structure of the neuromuscular junction in the various types of CMS, but have more recently expanded to the analysis of the genetic causes of CMS and the study of the multitude of cellular process that are altered in these rare disorders. The primary goal of my research is to advance our current knowledge of the pathogenesis of CMS that may lead to novel effective treatments. The long term goal of my research is to learn more about the function and biology of the neuromuscular synapse that may help decoding the great complexity of the function of the central nervous system.
B. Positions and Honors
1971-72 Physiology Assistant, University of Buenos Aires, Argentina
1974-75 Rotating Internship, University Medical Center of El Paso. El Paso, Texas.
1976-77 Resident of Neurology, Italian Hospital, Buenos Aires, Argentina
1978-79 Chief Resident of Neurology, Italian Hospital, Buenos Aires, Argentina
1979-82 Neurology Fellowship (Clinical Neurology), Queen’s University, Ontario, Canada
1980-81 Neuropathology Fellowship, Queen’s University, Ontario, Canada
1982-88 Clinical and Research Fellow, Neurology, University of Chicago, Chicago, Illinois
1988-91 Assistant Professor of Neurology, University of Chicago, Chicago, Illinois
1991-1997 Associate Professor of Neurology, University of California, Davis, California
1997-present Professor of Neurology, University of California, Davis, California
Other Professional Activities:
2009-2014 Director of the Clinical Neurophysiology Fellowship Program. UC Davis.
1991-present Director of the Neurology Electromyography Laboratory. UC Davis.
C. Contributions to Science
Maselli RA; Richman DP; Wollmann RL. Inflammation at the neuromuscular junction in myasthenia gravis. Neurology, 1991, Sept. 41(9):1497-504.
Maselli RA; Mass DP, Distad BJ, Richman DP. Anconeus muscle: a human muscle preparation suitable for in-vitro microelectrode studies. Muscle and Nerve. 1991 Dec. 14 (12):1189-92.
Maselli RA; Soliven BC. Analysis of the organophosphate-induced electromyographic response to repetitive nerve stimulation: paradoxical response to edrophonium and D-tubocurarine. Muscle and Nerve, 1991. Dec 14 (12):1189-92.
Dieperink ME, O’Neill A; Maselli R; Stefansson K. Experimental allergic neuritis in the SJL/J mouse: dysfunction of peripheral nerve without clinical signs. Journal of Neuroimmunology, 1991, Dec., 35(1-3):247-59.
Maselli RA; Burnett ME; Tonsgard JH. In-vitro microelectrode study of neuromuscular transmission in a case of botulism. Muscle and Nerve, 1992, Mar., 15(3):273-6.
Maselli RA; Cashman NR; Wollmann RL; Salazar-Grueso EF; Roos R. Neuromuscular transmission as a function of motor unit size in patients with prior poliomyelitis. Muscle and Nerve, 1992, June, 15(6):648-55.
Appelbaum JS; Roos RP; Salazar-Grueso EF; Buchman A; Iannaccone S; Glantz R; SiddiqueT; Maselli R. Intrafamilial heterogeneity in hereditary motor neuron disease. Neurology, 1992, Aug., 42(8):1488-92.
Maselli RA; Leung C. Analysis of anticholinesterase-induced neuromuscular transmission failure. Muscle and Nerve, 1993, May, 16(5):548-53.
Richman DP; Wollmann RL; Maselli RA; Gomez CM; Corey AL; Agius MA; Fairclough RH. Effector mechanisms of myasthenic antibodies. Annals of the New York Academy of Sciences, 1993, June, 681:264-73.
Maselli RA; Wollmann RL; Leung C; Distad B; Palombi S; Richman DP; Salazar-Gruieso EF; Roos RP. Neuromuscular transmission in amyotrophic lateral sclerosis. Muscle and Nerve. 1993. Nov., 16(11):1193-203.
Maselli RA. Pathophysiology of myasthenia gravis and Lamber-Eaton syndrome. Neurologic Clinics, 1994, May, 12(2):285-303.
Maselli RA; Wollmann R; Roos R. Function and ultrastructure of the neuromuscular junction in post-polio syndrome. Annals of the New York Academy of Sciences, 1995, May, 753:129-137.
Rivero A; Crovetto L; Lopez L; Maselli R; Nogues M. Single fiber electromyography of extraocular muscles: a sensitive method for the diagnosis of ocular myasthenia gravis. Muscle and Nerve, 1995, Sept., 18(9):943-947.
Gomez CM; Maselli R; Gammack J; Lasalde J; Tamamizu S; Cornblath DR; Lehar M; McNamee M; Kuncl RW. A beta-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome. Annals of Neurology, 1996, June, 39(6):712-723.
Mandler RN; Maselli RA. Stimulated single-fiber electromyography in wound botulism. Muscle and Nerve, 1996, 19(9):1171-1173.
Sheikh FS; Maselli RA. Unsuspected V nerve lesion resulting from perineural cancer spread detected by blink reflex. Muscle and Nerve, 1996, Dec. 19(12):1623-1625.
Maselli RA. End-plate electromyography: use of spectral analysis of end-plate noise. Muscle and Nerve, 1997, Jan. 20(1):52-58.
Gomez CM; Maselli R; Gundeck JE; Chao M; Day JW; Tamamizu S; Lasalde JA; McNamee M; Wollmann RL. Slow-channel transgenic mice: a model of postsynaptic organellar degeneration at the neuromuscular junction. Journal of Neuroscience, 1997, June, 17(11)4170-4179.
Maselli RA, Ellis W; Mandler RN; Sheikh F; Senton G; Knox S; Salari-Namin H; Agius M; Wollmann RL; Richman DP. Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study.
Muscle and Nerve, 1997, Oct., 20(10):1284-95.: Maselli, Ricardo A. 8
Bakshi N; Maselli RA; Gospe SM Jr; Ellis WG; McDonald C; Mandler RN. Fulminant demyelinating neuropathy mimicking cerebral death. Muscle and Nerve, 1997, Dec. 20(12):1595-1597.
Agius MA; Maselli RA; Zhu S; Fairclough RH; Lin MY; Ellis W. Rhodamine-labeled alpha-bungarotoxin allows visualization of end plates in congenital end plate acetylcholinesterase deficiency (CEAD). Annals of the New York Acad. of Sciences, 1998, May, 841:207-9.
Agius MA; Zhu S; Lee EK; Aarli JA; Kirvan C; Fairclough RH; Maselli R. Antibodies to AchR, synapse-organizing proteins, titin, and other muscle proteins in Morvan’s fibrillary chorea. Annals of the New York Acad. of Sciences, 1998, May, 841:522-524.
Gomez CM; Maselli R; Williams JM; Bhattacharyya BB; Wollmann RL; Day JW. Genetic manipulation of AchR responses suggests multiple causes of weakness in slow-channel syndrome. Annals of the New York Acad. of Sciences, 1998, May, 841:167-180.
Maselli RA. Pathogenesis of human botulism. Annals of the New York Acad. of Sciences, 1998, May, 841:122-139.
Richman DP; Agius,MA; Kirvan CA; Gomez CM; Fairclough RH; Dupon BL; Maselli RA. Antibody effector mechanisms in myasthenia gravis. The complement hypothesis. Annals of the New York Acad. Of Sciences, 1998, May, 841:450-465.
Lee Ek; Maselli RA; Ellis WG; Agius MA. Movran’s fibrillary chorea: a paraneoplastic manifestation of thymonma. Journal of Neurology, Neurosurgery and Psychiatry, 1998, Dec, 65(6):857-867.
Maselli RA, Kong DZ, Bowe CM, McDonald CM, Ellis WG, Agius MA, Gomez CM, Richman DP, Wollmann RL. Presynaptic congenital myasthenic syndrome due to quantal release deficiency. Neurology. 2001 Jul 24;57(2):279-89.
Gomez CM, Maselli RA, Vohra BP, Navedo M, Stiles JR, Charnet P, Schott K, Rojas L, Keesey J, Verity A, Wollmann RW, Lasalde-Dominicci J. Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. Ann Neurol. 2002 Jan;51(1):102-12.
Gomez, C.M., R.A. Maselli, B.P. Vohra, M. Navedo , J.R. Stiles, P. Charnet, K. Schott, L. Rojas, J. Keesey, A. Verity, R.L. Wollmann and J. Lasalde-Dominicci. Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. Annals of Neurology. 2002, 51(1):102-12.
Gomez, C.M., R.A. Maselli, J. Groshong, R.. Zayas, R.L. Wollmann, T. Cens and P. Charnet. Active calcium accumulation underlies severe weakness in a panel of mice with slow-channel syndrome. The Journal of Neuroscience. 2002, 22(15):6447-57.
Maselli, R.A., D. Chen, D. Mo, C. Bowe, G. Fenton, R.L. Wollmann. Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis. Muscle Nerve. 2003; 27(2):180-7.
Dunne, V., R.A. Maselli. Identification of pathogenic mutations in the human rapsyn gene. J Hum Genet 2003; 48(4):204-7.
Anor, S., D. Lipsitz, D.C. Williams, L. Tripp, N. Willits, R.A. Maselli R, R.A. LeCouteur RA. Evaluation of jitter by stimulated single-fiber electromyography in normal dogs. J Vet Intern Med 2003; 17(4):545-50.
Maselli, R.A., V. Dunne, S.I. Pascual-Pascual, C. Bowe, M. Agius, R. Frank, R.L. Wollmann RL. Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. Muscle Nerve 2003; 28(3):293-301.
Maselli, R.A., W. Books, V. Dunne. Effect of inherited abnormalities of calcium regulation on human neuromuscular transmission. Ann N Y Acad Sci 2003; 998:18-28.
Maselli, R.A., J. Wan, V. Dunne, M. Graves, R.W. Baloh, R.L. Wollmann, J. Jen. Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. Neurology 2003; 61(12):1743-8.
Vohra, B.P., J.S. Groshong, R.A. Maselli, M.A. Verity, R.L. Wollmann, C.M. Gomez. Focal caspase activation underlies the endplate myopathy in slow-channel syndrome.Ann Neurol 2004; 55(3):347-52.
Dunne, V, R.A. Maselli. Common founder effect of rapsyn N88K studied using intragenic markers. J Hum Genet. 2004;49(7): 366-9.
Navedo MF, Lasalde-Dominicci JA, Baez-Pagan CA, Diaz-Perez L, Rojas LV, Maselli RA, Staub J, Schott K, Zayas R, Gomez CM. Novel beta subunit mutation causes a slow-channel syndrome by enhancing activation and decreasing the rate of agonist dissociation. Mol Cell Neurosci. 2006 May-Jun;32(1-2):82-90. Epub 2006 Apr 19.
Maselli RA, Dris H, Schnier J, Cockrell JL, Wollmann RL. Congenital myasthenic syndrome caused by two non-N88K rapsyn mutations Clin Genet. 2007 Jul;72(1):63-5.
Hagerman RJ, Coffey SM, Maselli R, Soontarapornchai K, Brunberg JA, Leehey MA, Zhang L, Gane LW, Fenton-Farrell G, Tassone F, Hagerman PJ. Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome. Am J Med Genet;143(19):2256-60.
Denning L, Anderson JA, Davis R, Gregg JP, Kuzdenyi J, Maselli RA, High Throughput Genetic Analysis of Congenital Myasthenic Syndromes Using Resequencing Microarrays. PLoS. 2007 Sep 19;2(9):e918.
Soontarapornchai K, Maselli R, Fenton-Farrell G,Tassone F, Hagerman PJ, Hessl D, Hagerman RJ. Abnormal nerve conduction features in fragile X premutation carriers. Arch Neurol. 2008, 65(4): 495-498.
Anderson J, Ng J, Bowe C, MD, McDonald C, MD, Richman DP, Wollmann RL, Maselli RA. Variable Phenotype Associated with DOK7 Mutations. Muscle Nerve 2008. 37(4): 448-456.
Maselli RA, Ng J, Anderson J, Cagney O, Arredondo J, Williams C, Wessel HB, Abdel-Hamid H, Wollmann RL. Mutations in LAMB2 Causing a Severe Form of Synaptic Congenital Myasthenic Syndrome, J Med Gent. 2009. 2009 Mar;46(3):203-8.
Maselli, RA, Arredondo J, Cagney O, Ng J, Anderson J, Williams C, Soliven B, Wollmann Rl. Mutations in MUSK causing severe congenital myasthenic syndrome impair MuSK-Dok-7 interaction Hum Mol Genet. 2010 Jun 15;19(12):2370-9.
Maselli R, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S, Davis R, Gregg J, Sivak M, Konia T, Thomas K, Wollmann R. Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE Clin Genet. 2011 Nov;80(5):444-51.
Maselli RA, Henderson JD, Ng JJ, Follette D, Graves G, Wilson BW. Protection of Human Muscle Acetylcholinesterase from Soman by Pyridostigmine Bromide. Muscle Nerve. 2011. Muscle Nerve. 2011;43(4):591-5.
Richman DP, Nishi K, Morell SW, Chang JM, Ferns MJ, Wollmann RL, Maselli RA, Schnier J, Agius MA.
Acute severe animal model of anti-muscle-specific kinase myasthenia: combined postsynaptic and presynaptic changes. Arch Neurol. 2012 Apr;69(4):453-60.
Maselli RA, Fernandez JM, Arredondo J, Navarro C, Ngo M, Beeson D, Cagney O, Williams DC, Wollmann RL, Yarov-Yarovoy V, Ferns MJ. LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. Hum Genet. 2012 Jul;131(7):1123-35.
Maselli RA, Arredondo J, Ferns MJ, Wollmann RL Synaptic basal lamina-associated congenital myasthenic syndromes. Ann N Y Acad Sci. 2012 Dec;1275:36-48.
Maselli RA, Arredondo J, Nguyen J, Lara M, Ng F, Ngo M, Pham J, Yi Q, Stajich J, McDonald K, Hauser M, Wollmann R. Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia. Clin Genet. 2014 Feb;85(2):166-71.
Arredondo J, Lara M, Ng F, Gochez DA, Lee DC, Logia SP, Nguyen J, Maselli RA. COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina. Hum Genet. 2014 May;133(5):599-616.
Ram S, Devapriya IA, Fenton G, McVay L, Nguyen DV, Tassone F, Maselli RA, Hagerman RJ. Axonal neuropathy in female carriers of the fragile X premutation with fragile X-associated tremor ataxia syndrome.
Muscle Nerve. 2015 Aug;52(2):234-9.
Arredondo J, Lara M, Gospe SM Jr, Mazia CG, Vaccarezza M, Garcia-Erro M, Bowe CM, Chang CH, Mezei MM, Maselli RA. Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype-Phenotype Correlations. Hum Mutat. 2015 Sep;36(9):881-93.
Arnold WD, Feldman DH, Ramirez S, He L, Kassar D, Quick A, Klassen TL, Lara M, Nguyen J, Kissel JT, Lossin C, Maselli RA. Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. Ann Neurol. 2015 May;77(5):840-50.
Ng F, Lee DC, Schrumpf LA, Mazurek ME, Lee Lo V, Gill SK, Maselli RA. Effect of 3,4-diaminopyridine at the murine neuromuscular junction. Muscle Nerve. 2017 Feb;55(2):223-231.
Maselli RA, Arredondo J, Vázquez J,Chong JX, University of Washington Center for Mendelian Genomics, Bamshad,MJ, Nickerson DA, Lara M,Ng F, Lo VL, Pytel P, McDonald.C. Presynaptic congenital myasthenic syndrome with a homozygous sequence variant in LAMA5 combines myopia, facial tics and failure of neuromuscular transmission. AJHG. 2017 Aug;173(8):2240-2245.
Bevilacqua JA, Lara M, Díaz J, Campero M, Vázquez J, Maselli RA. Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile. Eur J Transl Myol. 2017 Sep 20;27(3):6832.
Maselli RA, Arredondo J, Vázquez J, Chong JX, Bamshad,MJ, Nickerson DA, Lara M,Ng F, Lo VL, Pytel P, McDonald.C. A Presynaptic Congenital Myasthenic Syndrome Attributed to a Homozygous Sequence Variant in LAMA5. Ann N Y Acad Sci. 2018. In press.
Maselli RA, Vázquez J, Schrumpf L, Arredondo J, Lara M, Strober JB, Pytel P, Wollmann R, Ferns M. Presynaptic Congenital Myasthenic Syndrome with Altered Synaptic Vesicle Homeostasis Linked to Compound Heterozygous Sequence Variants in RPH3A. Mol Genet Genomic Med. 2018. 2018 Feb 14. doi: 10.1002/mgg3.370.
Rudell JB, Maselli RA, Yarov-Yarovoy V, Ferns MJ.Pathogenic effects of agrin V1727F mutation are isoform-specific and decrease its expression and affinity for HSPGs and LRP4. Hum Mol Genet. 2019 Apr 17
Bissay V, Maselli RA. Phenotypical differences in two unrelated cases carrying identical DOK7 mutations. J Clin Neuromuscul Dis. 2019 Sep;21(1):30-34.
Maselli R, Van der Linden H, Ferns M. Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence. Submitted for publication.
D. Additional Information: Research Support and/or Scholastic Performance
Myasthenia Gravis Foundation of America (MGFA) Maselli (PI) 01/01/20-12/31/22
CSF delivery of AAV9-mediated gene therapy of congenital myasthenic syndrome due to CHAT mutations.