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Mervyn J. Monteiro

Mervyn J. Monteiro Ph.D.

Academic Title: Professor
Primary Appointment: Anatomy and Neurobiology
Secondary Appointments: Biochemistry and Molecular Biology, Neurology
Location: 20 North Pine Street, S642
Phone: (410) 706-8132
Fax: (410) 706-8184

Personal History:

I obtained my undergraduate degree from Queen Elizabeth College, University of London, and my Ph.D. from the MRC National Institute for Medical Research (NIMR), Mill Hill London. I stayed at the NIMR to study the molecular biology of cytoskeleton proteins. I then moved to the USA, where I trained with Dr. Don Cleveland, then at The Johns Hopkins University, Baltimore, on the molecular genetics of neurofilaments. In 1989, I obtained a faculty position at the Medical Biotechnology Center, University of Maryland Biotechnology Institute, which in 2010, merged with University of Maryland, Baltimore.

Research Interests:

We seek to understand the mechanisms that cause neurodegenerative diseases, with the aim of devising rational therapies to treat these diseases. We are particularly interested in the role that protein misfolding plays in the etiology of these diseases. The accumulation of misfolded and aggregated proteins is a common phenomenon seen in many neurodegenerative diseases. Abnormalities in protein accumulation arise because of defects in the quality control systems that normally function to recognize and eliminate misfolded proteins from cells.

A focus of our lab is to identify the molecular components and operations of the machinery that function to eliminate misfolded proteins from cells and how defects in these systems can lead to activation of signaling pathways causing disease. A particular focus is on proteins first identified by my lab—the human ubiquilin proteins - that function in protein degradation pathways. Mutations in ubiquilin genes have been found to cause neurodegenerative diseases.

A recent focus is geared toward understanding how mutations in one of these genes, UBQLN2, cause amyotrophic lateral sclerosis (ALS). We use a combination of cell and molecular biology, biochemical, and genetic approaches together with mammalian cell, nematode (C. elegans), and mouse models for our investigations. We recently developed several UBQLN2 mouse models of ALS that will allow us to investigate the molecular mechanisms that trigger disease and to test therapeutic strategies to halt disease.

Lab Personnel:

Irina Kovlyagina, Research Assistant
Nhat Thanh Le, Post-Doc


Selected Publications

Chang L and Monteiro MJ. (2015) Defective proteasome delivery of polyubiquitinated proteins by ubiquilin-2 proteins containing ALS mutations. PLoS One. 10(6) e0130162.

Gilpin K, Chang L and Monteiro MJ. (2015) ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between ubiquilin-2 and hnRNPA1. Hum Mol Gen 24:2565-2577.

Safren N, Chang L, Dziki, KM and Monteiro MJ. (2015) Signature changes in ubiquilin expression in the R6/2 mouse model of Huntington’s disease. Brain Research 1597: 37-46.

Safren N, El Ayadi A, Chang L, Terrillion CE, Gould TD, Boehning DF, and Monteiro MJ. (2014) Ubiquilin-1 overexpression increases the lifespan and delays accumulation of huntingtin aggregates in the R6/2 mouse model of Huntington’s disease. PLoS One 9(1). e87513.

Chen Z, Zhong Y, Wang Y, Xu S, Liu Z, Baskakov IV, Monteiro MJ, Karbowski M, Shen Y, Fang S. (2013) Ubiquitination-induced fluorescence complementation (UiFC) for detection of K48 ubiquitin chains in vitro and in live cells. PLoS One. E73482.

Brettschneider J, Van Deerlin, VM, Robinson JL, Kwong L, Lee EB, Ali YO,  Safren N, Monteiro MJ, Toledo JB, Elman L,  McCluskey L, Irwin DJ, Grossman M, Molina L, Lee VM-Y, Trojanowski JQ. (2012) Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion. Acta Neuropathologica 123:825-839.

Klionsky et al., (2012) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 8:445-544.

Wang H, Kabrowski, M and Monteiro MJ (2011) Mitochondrial Dynamics in Huntington’s disease: A dance of fate. In Mitochondrial dynamics and neurodegeneration. Ed Bingwei Lu. Springer.

Zhong Y, Wang Y, Yang H, Ballar P, Lee Y-J, Ye Y, Monteiro MJ, and Fang S (2011) Importin b interacts with the ER-associated degradation machinery and promotes ubiquitination and degradation of mutant a1-antitrypsin. J Biol Chem, 286:33921-33930.

Wang Y, Ballar P, Zhong Y, Zhang X, Liu C, Zhang Y-J, Monteiro MJ, Li J, and Fang S (2011) SVIP induces localization of p97/VCP to the plasma and lysosomal membranes and regulates autophagy. PLoS One:e24478.

Ugolino J, Fang S, Kubisch C and Monteiro MJ (2011) Mutant Atp13a2 proteins involved in parkinsonism are degraded by ER-associated degradation and sensitize cells to ER-stress induced cell death. Hum Mol Genet, 20:3565-3577.

Dong G, Ferguson JM, Duling AJ, Nicholas RG, Zhang D, Rezvani K, Fang S, Monteiro MJ, Li S, Li XJ and Wang H (2011) Modeling Pathogenesis of Huntington's Disease with Inducible Neuroprogenitor Cells. Cell Mol Neurobiol, 31:737-47.

Rothenberg C and Monteiro MJ (2010) Ubiquilin at a crossroads in protein degradation pathways. Autophagy, 6:979-980.

Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, Ugolino J, Fang S, Cuervo AM, Nixon RA and Monteiro MJ (2010) Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum Mol Genet, 19:3219-3232. (Journal Cover)

Yang H, Liu C, Zhong Y, Luo S, Monteiro MJ and Fang, S (2010) Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP. PLoS One, 5:e8905.

Wang H, Lim PJ, Karbowski M and Monteiro MJ (2009) Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet, 18:737-752.

Lim PJ, Danner R, Liang J, Doong H, Harman C, Srinivasan D, Rothenberg C, Wang H, Ye Y, Fang S and Monteiro MJ (2009) Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD. J Cell Biol, 187:201-217.

Yang H, Zhong X, Ballar P, Luo S, Shen Y, Rubinsztein DC, Monteiro MJ and Fang S (2007) Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin. Exp Cell Res, 313:538-550.

Wang H and Monteiro MJ (2007) Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity. Exp Cell Res, 313:2810-2820.

Wang H and Monteiro MJ (2007) Ubiquilin interacts and enhances the degradation of expanded-polyglutamine proteins. Biochem Biophys Res Commun, 360:423-427.

Ford DL and Monteiro MJ (2007) Studies of the role of ubiquitination in the interaction of ubiquilin with the loop and carboxyl terminal regions of presenilin-2. Biochemistry, 46:8827-8837.

White C, Yang J, Monteiro MJ and Foskett JK (2006) CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the InsP3 receptor Ca2+ release channel. J Biol Chem, 281:20825-20833.

Wang H, Lim PJ, Yin C, Rieckher M, Vogel BE and Monteiro MJ (2006) Suppression of polyglutamine-induced toxicity in cell and animal models of Huntington's disease by ubiquilin. Hum Mol Genet, 15:1025-1041.

Liang J, Yin C, Doong H, Fang S, Peterhoff C, Nixon RA and Monteiro MJ (2006) Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated protein degradation. J Cell Sci, 119:4011-4024.

Ford DL and Monteiro MJ (2006) Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins. Biochem J, 399:397-404.

Massey LK, Mah AL and Monteiro MJ (2005) Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin. Biochem J, 391:513-525.

Zhu J, Stabler SM, Ames JB, Baskakov I and Monteiro MJ (2004) Calcium binding sequences in calmyrin regulate interaction with presenilin-2. Exp Cell Res, 300:440-454.

Mical TI, Luther PW and Monteiro MJ (2004) Intracellular assembly and sorting of intermediate filament proteins: role of the 42 amino acid lamin insert. Exp Cell Res, 295:183-193.

Massey LK, Mah AL, Ford DL, Miller J, Liang J, Doong H and Monteiro MJ (2004) Overexpression of ubiquilin decreases ubiquitination and degradation of presenilin proteins. J Alzheimers Dis, 6:79-92.

Gu L, Troncoso JC, Wade JB and Monteiro MJ (2004) In vitro assembly properties of mutant and chimeric intermediate filament proteins: insight into the function of sequences in the rod and end domains of IF. Exp Cell Res, 298:249-261.

Feng P, Scott CW, Cho NH, Nakamura H, Chung YH, Monteiro MJ and Jung JU (2004) Kaposi's sarcoma-associated herpesvirus K7 protein targets a ubiquitin-like/ubiquitin-associated domain-containing protein to promote protein degradation. Mol Cell Biol, 24:3938-3948.

Miroy G and Monteiro MJ (2002) Expression and purification of a convenient Ca2+-calmodulin-dependent protein kinase II GST-fusion substrate. Protein Expr Purif, 26:343-348.

Judge SI, Yeh JZ, Goolsby JE, Monteiro MJ and Bever CT, Jr (2002) Determinants of 4-aminopyridine sensitivity in a human brain kv1.4 k(+) channel: phenylalanine substitutions in leucine heptad repeat region stabilize channel closed state. Mol Pharmacol, 61:913-920.

Mah AL, Perry G, Smith MA and Monteiro MJ (2000) Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation. J Cell Biol, 151:847-862.

Janicki SM, Stabler SM and Monteiro MJ (2000) Familial Alzheimer's disease presenilin-1 mutants potentiate cell cycle arrest. Neurobiol Aging, 21:829-836.

Stabler SM, Ostrowski LL, Janicki SM and Monteiro MJ (1999) A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. J Cell Biol, 145:1277-1292.

Raina AK, Monteiro MJ, McShea A and Smith MA (1999) The role of cell cycle-mediated events in Alzheimer's disease. Int J Exp Pathol, 80:71-76.

Judge SI, Monteiro MJ, Yeh JZ and Bever CT. (1999) Inactivation gating and 4-AP sensitivity in human brain Kv1.4 potassium channel. Brain Res, 831:43-54.

Janicki SM and Monteiro MJ (1999) Presenilin overexpression arrests cells in the G1 phase of the cell cycle. Arrest potentiated by the Alzheimer's disease PS2(N141I)mutant. Am J Pathol, 155:135-144.

Mical TI and Monteiro MJ (1998) The role of sequences unique to nuclear intermediate filaments in the targeting and assembly of human lamin B: evidence for lack of interaction of lamin B with its putative receptor. J Cell Sci, 111:3471-3485.

Janicki S and Monteiro MJ (1997) Increased apoptosis arising from increased expression of the Alzheimer's disease-associated presenilin-2 mutation (N141I). J Cell Biol, 139:485-495.

Xiao J, Perry G, Troncoso J and Monteiro MJ (1996) alpha-calcium-calmodulin-dependent kinase II is associated with paired helical filaments of Alzheimer's disease. J Neuropathol Exp Neurol, 55:954-963.

Starr R, Hall FL and Monteiro MJ (1996) A cdc2-like kinase distinct from cdk5 is associated with neurofilaments. J Cell Sci, 109:1565-1573.

Starr R, Attema B, DeVries GH and Monteiro MJ (1996) Neurofilament phosphorylation is modulated by myelination. J Neurosci Res, 44:328-337.

Monteiro MJ and Mical TI (1996) Resolution of kinase activities during the HeLa cell cycle: identification of kinases with cyclic activities. Exp Cell Res, 223:443-451.

Starr R, Xiao J and Monteiro MJ (1995) Production of monoclonal antibodies against neurofilament associated proteins: demonstration of association with neurofilaments by a coimmunoprecipitation method. J Neurochem, 64:1860-1867.

Hsu C, Janicki S and Monteiro MJ (1995) The first intron of the mouse neurofilament light gene (NF-L) increases gene expression. Brain Res Mol Brain Res, 32:241-251.

Xiao J and Monteiro MJ (1994) Identification and characterization of a novel (115 kDa) neurofilament-associated kinase. J Neurosci, 14:1820-1833.

Monteiro MJ, Hicks C, Gu L and Janicki S (1994) Determinants for intracellular sorting of cytoplasmic and nuclear intermediate filaments. J Cell Biol, 127:1327-1343.