Michael J. Ferns, Ph.D.

Clinical Interests

My clinical interest is in diseases of cholinergic neuromuscular and autonomic synapses, such myasthenia gravis and congenital myasthenic syndrome. Our aim is to understand the pathological basis for these diseases at a molecular level and to define new therapeutic targets for the treatment of these disorders. My research interest is the cellular and molecular basis of synapse formation in the mammalian nervous system. Synapse formation is critical for the development, maintenance, and plasticity of the nervous system and perturbations in synaptic structure and function have been implicated in a range of neurological disorders. My research focuses on cholinergic neuromuscular and interneuronal synapses in teh peripheral nervous system. Our main aims are (1) to define the extracellular synaptogenic factors that regulate the formation and maintenance of these synapses; (2) to define the intracellular protein interactions that regulate the localization and trafficking of nicotinic acetylcholine receptors (AChR) at these synapses; and (3) to establish how dysregulation of AchR localization contributes to diseases such as myasthenia gravis and congenital myastenic syndrome.

Title:

Professor

Department:

Anesthesiology

Division:

Anesthesiology/Physiology

Education:

Ph.D., University of Western Australia, Perth, Crawley, 1988
B.Sc., University of Otago, Dunedin, 1983

Select Recent Publications:

Lee Y, Rudell J, Ferns M. Rapsyn interacts with the muscle acetylcholine receptor via alpha-helical domains in the alpha, beta, and epsilon subunit intracellular loops. Neuroscience. 2009 Sep 29;163(1):222-32. Epub 2009 May 29.

Lee Y, Rudell J, Yechikhov S, Taylor R, Swope S, Ferns M. Rapsyn carboxyl terminal domains mediate muscle specific kinase-induced phosphorylation of the muscle acetylcholine receptor. Neuroscience. 2008 Jun 2;153(4):997-1007. Epub 2008 Mar 18.

Borges LS, Yechikhov S, Lee YI, Rudell JB, Friese MB, Burden SJ, Ferns MJ. Identification of a motif in the acetylcholine receptor beta subunit whose phosphorylation regulates rapsyn association and postsynaptic receptor localization. J Neurosci. 2008 Nov 5;28(45):11468-76.

Gingras J, Rassadi S, Cooper E, Ferns M. Synaptic transmission is impaired at neuronal autonomic synapses in agrin-null mice. Dev Neurobiol. 2007 Apr;67(5):521-34.

Kumar P, Ferns MJ, Meizel S. Identification of agrinSN isoform and muscle-specific receptor tyrosine kinase in sperm. Biochem and Biophys Res Comm, 342:522-528.

Gingras J, Spicer J, Altares M, Zhu Q, Kuchel GA, Ferns M. Agrin becomes concentrated at neuroeffector junctions in developing rodent urinary bladder. Cell and Tissue Research, 320:115-125.

Moransard M, Borges LS, Willmann R, Marangi PA, Brenner HR, Ferns MJ, Fuhrer C. Agrin regulates rapsyn interaction with surface acetylcholine receptors, and this underlies cytoskeletal anchoring and clustering. J Biol Chem, 278(9):7350-9.

Gingras J, Rassadi S, Cooper E, Ferns M. Agrin plays an organizing role in the formation of sympathetic synapses. J Cell Biol, 157(6):1109-1118.

Borges LS, Lee Y, Ferns M. Dual role for calcium in agrin signaling and acetylcholine receptor clustering. J Neurobiol, 50(1):69-79.

Ferns M, Carbonetto S. Challenging the neurocentric view of neuromuscular synapse formation. Neuron, 30:311-314.

Gingras J, Ferns MJ. Expression and localization of agrin during sympathetic synapse formation in vitro. J Neurobiol, 48(3):228-242.

Borges LS , Ferns M. Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clustering. J Cell Biol, 153(1):1-11.

Grow WA, Ferns M, Gordon H. A mechanism for acetylcholine receptor clustering distinct from agrin signaling. Dev Neurosci, 21:436-443.

Grow WA, Ferns M, Gordon H. Agrin-independent activation of the agrin signal transduction pathway. J Neurobiol, 40:356-365.

Gramolini AO, Burton EA, Tinsley JM, Ferns MJ, Cartaud A, Cartaud J, Davies KE, Lunde JA, Jasmin BJ. Muscle and neural isoforms of agrin increase utrophin expression in cultured myotubes via a transcriptional regulatory mechanism. J Biol Chem, 273(2):736-43.

Jacobson C, Montanaro F, Lindenbaum M, Carbonetto S, Ferns MJ. Alpha-dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin=MuSK signaling. J Neurosci, 18(16):6340-6348.

Wang ZZ, Fuhrer C, Shtrom S, Sugiyama JE, Ferns MJ, Hall ZW. The nicotinic acetylcholine receptor at the neuromuscular junction: assembly and tyrosine phosphorylation. Cold Spring Harbor Symposia on Quantitative Biology, Function and Dysfunction in the Nervous System, 61:363-71.

Ferns MJ, Deiner M, Hall Z. Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation. J Cell Biol, 132(5):937-944.

Bowen DC, Sugiyama J, Ferns M, Hall ZW. Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin. J Neurosci, 16(12):3791-3797.

Ferns MJ, Hollyday M. Chick wing innervation. III. Formation of axon collaterals in developing peripheral nerves. J Comp Neurol, 357(2):272-80.

Ferns MJ, Hollyday M. Motor innervation of dorsoventrally reversed wings in chick/ quail chimeric embryos. J Neurosci, 13(6):2463-76.

Ferns MJ, Campanelli JT, Hoch W, Scheller RH, Hall Z. The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans. Neuron, 11(3):491-502.

Hoch W, Ferns M, Campanelli JT, Hall ZW, Scheller RH. Developmental regulation of highly active alternatively spliced forms of agrin. Neuron, 11(3):479-490.

Campanelli JT, Ferns MJ, Hoch W, Rupp F, von Zastrow M, Hall Z, Scheller RH. Agrin: a synpatic basal lamina protein that regulates development of the neuromuscular juntion. Cold Spring Harbor Symposia on Quantitative Biology, LVII:461-472.

Ferns MJ, Hall ZW. How many agrins does it take to make a synapse? Cell, 70(1):1-3.

Ferns M, Hoch W, Campanelli JT, Rupp F, Hall ZW, Scheller RH. RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes. Neuron, 8:1079-1086.

Lamb AH, Ferns MJ, Klose K. Peripheral competition in the control of sensory neuron numbers in Xenopus frogs reared with a single bilaterally innervated hindlimb. Dev Brain Research, 45(1):149-54.