Monteiro, Mervyn | University of Maryland School of Medicine

Academic Title:

Professor

Primary Appointment:

Neurobiology

Secondary Appointment(s):

BioChemistry&Molecular Biology, Neurology

Email:

monteiro@som.umaryland.edu

Location:

406 Howard Hall, 660 West Redwood Street

Phone (Primary):

(410) 706-8132

Fax:

(410) 706-8184

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Education and Training

I was born in Mombasa, Kenya, where I completed my high school education. I then moved to England and graduated from Queen Elizabeth College, University of London, obtaining a BSc degree with 1st class honors in Microbiology and a Ph.D. from the MRC National Institute for Medical Research (NIMR), which is now part of The Francis Crick Institute. I then conducted postdoctoral studies at NIMR and then moved to the USA, where I trained with Dr. Don Cleveland, then at The Johns Hopkins University, Baltimore. In 1989, I obtained a faculty position at the Medical Biotechnology Center, University of Maryland Biotechnology Institute, which in 2010, was incorporated into the University of Maryland, Baltimore.

Biosketch

1979 BSc Microbiology (1st Class Honors), Queen Elizabeth College, University of London, England

1983 PhD Microbiology and Molecular Biology, National Institute for Medical Research (MRC), Mill Hill, London

1983-1986 Post-Doc Molecular Biology, National Institute for Medical Research (MRC), Mill Hill, London

1986-1989 Post-Doc Molecular Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland

1989-1996 Assistant Professor, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland

1996-2002 Associate Professor, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland

2002-2010 Professor, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland

2010- Professor, University of Maryland School of Medicine, Baltimore, Maryland

Research/Clinical Keywords

Protein misfolding, Neurodegenerative diseases, ALS, Alzheimer's, ubiquilin, proteasome, autophagy

Highlighted Publications

Lin BC, Phung TH, Higgins NR, Greenslade JE, Prado MA, Finley D, Karbowski M, Polster, BM and Monteiro MJ. (2021) ALS/FTD mutations in UBQLN2 are linked to mitochondrial dysfunction through loss-of-function in mitochondrial protein import. Hum Mol Genet, 30:1230-1246.

Wang S, Tatman M, and Monteiro, MJ. (2020) Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD. Acta Neuropathologica Communications 8:164, https://doi.org/10.1186/s40478-020-01039-9.

Wu JJ, Cai A, Greenslade JE, Higgins NR, Fan C, Le NTT, Tatman MD, Whiteley AA, Prado MA, Dieriks BV, Curtis MA, Shaw CE, Siddique T, Faull RLM, Scotter EL, Finley D, and Monteiro MJ. (2020) ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc Natl Acad Sci USA, 117: 15230-41.

Le NTT, Chang L, Kovlyagina I, Georgiou P, Safren N, Braunstein KE, Kvarta MD, Van Dyke AM, LeGates TA, Philips T, Morrison BM, Thompson SM, Puche AC, Gould TD, Rothstein JD, Wong PC and Monteiro MJ. (2016) Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS-FTD-linked UBQLN2 mutations. Proc Natl Acad Sci USA, 113:E7580-89.

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

Safren N, El AyadiA, ChangL, 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.

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.

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)

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.

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.

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.

Additional Publication Citations

Lin BC, Higgins NR, Phung TH and Monteiro MJ. (2021) UBQLN proteins in health and disease with a focus on UBQLN2 in ALS/FTD. State-of-the-Art Review. FEBS J. doi:10.1111/febs.16129

Higgins NR, Greenslade JE, Wu JJ, Miranda, E, Galliciotti G, and Monteiro MJ. (2021) Serpin neuropathology in the P497S mouse model of ALS/FTD. Brain Pathol. Doi:1111/bpa.12948.

Whiteley AM, Prado MA, de Poot SAH, Paulo JA, Ashton M, Dominguez S, Weber M, Ngu H, Szpyt J, Jedrychowski MP, Easton A, Gygi SP, Kurz T, Monteiro MJ, Brown EJ, and Finley D. (2021) Global proteomics of Ubqln2-based murine models of ALS. Journal of Biological Chemistry 296:100153.

Wang S, Tatman M, and Monteiro, MJ. (2020) Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD. Acta Neuropathologica Communications 8:164, https://doi.org/10.1186/s40478-020-01039-9.

Higgins, N, Lin, B and Monteiro MJ. (2019) Lou Gehrig’s Disease (ALS): UBQLN2 mutations strike out of phase. Structure 27:879-881.

Harman, CA and Monteiro MJ. (2019) The specificity of ubiquitin binding to ubiquilin-1 is regulated by sequences besides its UBA domain. Biochim Biophys Acta Gen Subj S0304-4165(19)30151-5.doi:10.1016/jbbagen.2019.06.002.

Ugolino J, Dziki KM, Kim A, Wu JJ, Vogel BE and Monteiro MJ. (2019) Overexpression of human Atp13a2Isoform1 protein protects cells against manganese and starvation-induced toxicity. PLoS ONE e0220849.

Katorcha E, Makarava N, Lee YJ Lindberg I, Monteiro MJ, Kovacs G, Baskakov, IV. (2017) Cross-seeding of prions by aggregated alpha-synuclein leads to transmissible spongiform encephalopathy. PLos Pathogens 13(8)e1006563.

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, ChangL, 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.

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, WangY, YangH, BallarP, LeeY-J, YeY, Monteiro MJ, and FangS (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.

Mercy MR, Troncoso JC, Monteiro MJ. (1992). A new series of trpE vectors that enable high expression of non-fusion proteins in bacteria. Protein Expression and Purification 3:57-64.

Cleveland DW, Monteiro MJ, Wong PC, Gill SR, Gearhart JD, Hoffman PN. (1991). Involvement of neurofilaments in the radial growth of axons. J. Cell Sci. 15:85-95.

Gill SR, Wong PC, Monteiro MJ, Cleveland DW. (1990). Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit. J. Cell Biol. 111:2005-2019.

Monteiro MJ, Hoffman PN, Gearhart JD, Cleveland DW. (1990). Expression of neurofilament-L in both neuronal and non-neuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber. J. Cell Biol. 111:1543-1557.

Monteiro MJ, Cleveland DW. (1989). Expression of NF-L and NF-M in fibroblasts reveals co-assembly of neurofilament and vimentin subunits. J. Cell Biol. 108:579-593.

Monteiro MJ, Cleveland DW. (1988). Sequence of chicken cβ7 tubulin. Analysis of a complete set of vertebrate β-tubulin isotypes. J. Mol. Biol. 199:439-446.

Research Interests

My laboratory studies the protein degradation systems that function in the removal of misfolded proteins from cells, failure of which has been linked to disease, particularly neurodegenerative diseases. A central focus of our work is the human ubiquilin (UBQLN) proteins, which function in protein folding and degradation pathways. A major effort of this work is learning about how mutations in UBQLN2 cause amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD). We use a combination of cell biology, biochemical, and molecular genetic approaches together with mammalian cell and mouse models for our investigations. We recently developed several UBQLN2 mouse models of ALS/FTD, which we are using to decipher the mechanisms underlying ALS/FTD pathogenesis and to test therapeutic strategies to halt disease.