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Michael Myre

Michael Myre faculty headshot image
Dr. Michael MyreAssistant Professor
  • CollegeCollege of Sciences
  • DepartmentBiological Science
  • OfficeOlsen Hall - 512
  • EmailMichael_Myre@uml.edu

Research Interests

Huntington's disease, Batten disease, Dictyostelium, calcium signaling, cell-cell adhesion, chemotaxis, cellular homeostasis

My current research program characterizes the cellular and molecular pathways that cause neurodegenerative disorders. Huntington’s disease (HD) is a neurodegenerative disorder caused by mutation in a normally polymorphic region of the huntingtin (Htt) protein. The mutation that causes disease is the expansion of glutamine residues referred to as the polyQ domain (> 37 Q's). HD is a dominantly inherited disease characterized by motor, cognitive and behavioral symptoms, with loss of medium sized spiny neurons in the striatum. There is no therapeutic cure, just palliative care, and death follows between 10-15 years later.While there have been many studies to investigate the physical features of polyQ alone or polyQ embedded in polypeptides, little is known about the molecular impact of the polyQ region on the structure and function of the full-length Htt protein, except that it does not promote ‘self-aggregation’ of the Htt molecule. Thus, alternate model organism strategies are badly needed to complement and facilitate our understanding of the structure-function relationship that exists between the polyQ domain and huntingtin function.

I have developed a deficiency model in the genetically tractable organism Dictyostelium. Strains without the htt gene show that it is critical for cell adhesion, ion homeostasis, cAMP- and Ca2+ chemotaxis, cell polarity and cell fate (Myre, 2011; LoSardo, 2012; Thompson, 2014, Wessels, 2014). These processes have subsequently been found to be altered in various mammalian models of HD.

Specialties: recombinant DNA technologies, nucleic acid sequencing, RNA silencing, gene knockout, RNA purification and analysis by qRT-PCR and RNA-seq, protein analysis using Western blotting, antibody production, immunofluorescence, cell transfection, mammalian cell culture, microscopy (e.g., confocal), flow cytometry in the analysis of the cell cycle and design of synthetic genes for optimal expression in bacteria, yeast and mammalian cells.

Education

  • Ph D: Molecular Cell Biology, (2005), University of Toronto - Toronto
  • BS: Biology, (1999), University of Toronto - Toronto

Awards and Honors

  • CHDI Foundation Inc., Research Fellowship (2009), Scholarship/Research - Massachusetts General Hospital
  • Edward R. and Anne G. Lefler Postdoctoral Fellowship (2006), Scholarship/Research - Harvard Medical School
  • Ontario Graduate Scholarship in Science (2002), Scholarship/Research - University of Toronto
  • Graduate Scholarship in Science and Technology (2001), Scholarship/Research - Upjohn Pharmacia

Publications

  • Huber, R.J., Myre, M., Cotman, S.L. (2016) "Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis.," Cell adhesion & migration pp. 1-20
  • O'Day, D.H., Eshak, K., Myre, M. (2015) "Calmodulin Binding Proteins and Alzheimer's Disease.," Journal of Alzheimer's disease : JAD 46:3 pp. 553-69
  • Huber, R.J., Myre, M., Cotman, S.L. (2014) "Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3.," PloS one 9:10 pp. e110544
  • Wessels, D., Lusche, D.F., Scherer, A., Kuhl, S., Myre, M., Soll, D.R. (2014) "Huntingtin regulates Ca(2+) chemotaxis and K(+)-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H(+) exchanger Nhe1, in a model developmental system: insights into its possible role in Huntington?s disease.," Developmental biology 394:1 pp. 24-38
  • Kovács-Bogdán, E., Sancak, Y., Kamer, K.J., Plovanich, M., Jambhekar, A., Huber, R.J., Myre, M., Blower, M.D., Mootha, V.K. (2014) "Reconstitution of the mitochondrial calcium uniporter in yeast.," Proceedings of the National Academy of Sciences of the United States of America 111:24 pp. 8985-90
  • Thompson, M.N., MacDonald, M.E., Gusella, J.F., Myre, M. (2014) "Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum.," Journal of Huntington's disease 3:3 pp. 261-71
  • Lo Sardo, V., Zuccato, C., Gaudenzi, G., Vitali, B., Ramos, C., Tartari, M., Myre, M., Walker, J.A., Pistocchi, A., Conti, L., Valenza, M., Drung, B., Schmidt, B., Gusella, J., Zeitlin, S., Cotelli, F., Cattaneo, E. (2012) "An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.," Nature neuroscience 15:5 pp. 713-21
  • Myre, M. (2012) "Clues to ?-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum.," Journal of biomedical science 19: pp. 41
  • Suarez, A., Huber, R.J., Myre, M., O'Day, D.H. (2011) "An extracellular matrix, calmodulin-binding protein from Dictyostelium with EGF-like repeats that enhance cell motility.," Cellular signalling 23:7 pp. 1197-206
  • Myre, M., Lumsden, A.L., Thompson, M.N., Wasco, W., MacDonald, M.E., Gusella, J.F. (2011) "Deficiency of huntingtin has pleiotropic effects in the social amoeba Dictyostelium discoideum.," PLoS genetics 7:4 pp. e1002052
  • McMains, V.C., Myre, M., Kreppel, L., Kimmel, A.R. (2010) "Dictyostelium possesses highly diverged presenilin/gamma-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/gamma-secretase complex.," Disease models & mechanisms 3:9-10 pp. 581-94
  • Myre, M., Washicosky, K., Moir, R.D., Tesco, G., Tanzi, R.E., Wasco, W. (2009) "Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1.," Cellular signalling 21:4 pp. 567-76
  • O'Day, D.H., Poloz, Y., Myre, M. (2009) "Differentiation inducing factor-1 (DIF-1) induces gene and protein expression of the Dictyostelium nuclear calmodulin-binding protein nucleomorphin.," Cellular signalling 21:2 pp. 317-23
  • O'Day, D.H., Suhre, K., Myre, M., Chatterjee-Chakraborty, M., Chavez, S.E. (2006) "Isolation, characterization, and bioinformatic analysis of calmodulin-binding protein cmbB reveals a novel tandem IP22 repeat common to many Dictyostelium and Mimivirus proteins.," Biochemical and biophysical research communications 346:3 pp. 879-88
  • Myre, M., O'Day, D.H. (2005) "An N-terminal nuclear localization sequence but not the calmodulin-binding domain mediates nuclear localization of nucleomorphin, a protein that regulates nuclear number in Dictyostelium.," Biochemical and biophysical research communications 332:1 pp. 157-66
  • O'Day, D.H., Chatterjee-Chakraborty, M., Wagler, S., Myre, M. (2005) "Isolation and characterization of Dictyostelium thymidine kinase 1 as a calmodulin-binding protein.," Biochemical and biophysical research communications 331:4 pp. 1494-502
  • Myre, M., O'Day, D.H. (2004) "Dictyostelium nucleomorphin is a member of the BRCT-domain family of cell cycle checkpoint proteins.," Biochimica et biophysica acta 1675:1-3 pp. 192-7
  • Myre, M., O'Day, D.H. (2004) "Calmodulin binds to and inhibits the activity of phosphoglycerate kinase.," Biochimica et biophysica acta 1693:3 pp. 177-83
  • Myre, M., O'Day, D.H. (2004) "Dictyostelium calcium-binding protein 4a interacts with nucleomorphin, a BRCT-domain protein that regulates nuclear number.," Biochemical and biophysical research communications 322:2 pp. 665-71
  • O'Day, D.H., Myre, M. (2004) "Calmodulin-binding domains in Alzheimer's disease proteins: extending the calcium hypothesis.," Biochemical and biophysical research communications 320:4 pp. 1051-4
  • Myre, M., O'Day, D.H. (2002) "Nucleomorphin. A novel, acidic, nuclear calmodulin-binding protein from dictyostelium that regulates nuclear number.," The Journal of biological chemistry 277:22 pp. 19735-44