I grew up in Kenya, where I obtained my early education. At the age of 18, I moved to England where I continued my schooling, graduating in 1979 with 1st class honors in Microbiology from Queen Elizabeth College, University of London. I then conducted research at the MRC National Institute for Medical Research (NIMR), Mill Hill, London, under the supervision of Drs. Michael Sargent and Patrick Piggot, studying termination of DNA replication in Bacillus subtilis, and obtained my PhD degree in 1983. I stayed at NIMR as an MRC fellow for three more years studying actin and tubulin genes in Physarum polycephalum. In 1986, I came to the USA to work with Dr. Don Cleveland, then at The Johns Hopkins University, Baltimore, Maryland, where I initiated transgenic studies of neurofilament genes in mice. In 1989, I obtained a faculty position at the Medical Biotechnology Center (MBC), University of Maryland Biotechnology Institute, where I rose to the rank of Professor. In January 2010, the MBC was absorbed into the University of Maryland, Baltimore campus, where I now reside.
The major focus of the laboratory is directed toward an understanding of the molecular mechanisms that cause neurodegeneration, with the aim of devising rational therapies to treat and prevent human neurodegenerative diseases. Toward this goal we are studying the function and dysfunction of genes in which mutations have been found to cause Alzheimer, Huntington, and Parkinson diseases. We are particularly interested in the role that protein misfolding and aggregation plays in neurodegeneration. The accumulation of misfolded and aggregated proteins in the brain is a common and recurring theme seen in most, if not all, neurodegenerative diseases. Protein accumulation is though to arise because of defects in the quality control systems that normally function to fold, recognize, and eliminate misfolded proteins from cells. We are studying the composition and operation of the machinery that functions to dispose of misfolded proteins from cells and how defects in these systems can lead to activation of signaling pathways causing disease. We use a combination of cell biology, molecular biology, biochemistry, and genetic approaches together with mammalian cell, worm (C. elegans), and mouse models to discover the mechanisms that cause neurodegeneration and to test and validate candidate approaches to prevent and cure neurodegenerative diseases.
Lydia Chang, Research Assistant
Kathleen Gilpin, PhD Student
Nathaniel Safren, PhD Student
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, MonteiroMJ, and FangS (2011) Importin beta interacts with the ER-associated degradation machinery and promotes ubiquitination and degradation of mutant alpha1-antitrypsin. JBiolChem, 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.