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Lisa McConlogue, PhD

TitleProfessor
InstitutionUniversity of California San Francisco
DepartmentBiochemistry and Biophysics
Address533 Parnassus Avenue
San Francisco CA 94117
Phone415-476-4836
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    Collapse Overview 
    Collapse Overview
    The McConlogue laboratory focuses on both understanding the mechanisms involved in neurodegeneration driven by misfolding-prone proteins and in developing therapeutic approaches to treat neurological diseases such as Alzheimer’s and Parkinson’s diseases (AD and PD). We are particularly interested in understanding the pathogenic role and functional perturbation of intrinsically disordered proteins (IDP) that, due to their unique structural characteristics and key functional roles, lead to diseases of amyloid-type misfolding including cancer and neurodegenerative diseases.
    Our current focus is on understanding and blocking the pathogenic processes of a-Synuclein (a-Syn), an IDP that plays a central role in PD and also contributes to AD. We are developing small molecules that act as chaperones restoring the native structure and function of a-Syn under disease conditions to both probe the pathogenic mechanisms of a-Syn misfolding and malfunction, and to develop therapies to treat PD, AD and related diseases.


    Collapse Research 
    Collapse Research Activities and Funding
    Small-Molecule Pharmacological Chaperones to Prevent Synuclein Transmission
    NIH/NINDS R21NS092897Aug 1, 2015 - Jul 31, 2017
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Pickhardt M, Neumann T, Schwizer D, Callaway K, Vendruscolo M, Schenk D, St George-Hyslop P, Mandelkow EM, Dobson CM, McConlogue L, Mandelkow E, Tóth G. Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies. Curr Alzheimer Res. 2015; 12(9):814-28. PMID: 26510979.
      View in: PubMed
    2. Tóth G, Gardai SJ, Zago W, Bertoncini CW, Cremades N, Roy SL, Tambe MA, Rochet JC, Galvagnion C, Skibinski G, Finkbeiner S, Bova M, Regnstrom K, Chiou SS, Johnston J, Callaway K, Anderson JP, Jobling MF, Buell AK, Yednock TA, Knowles TP, Vendruscolo M, Christodoulou J, Dobson CM, Schenk D, McConlogue L. Targeting the intrinsically disordered structural ensemble of a-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease. PLoS One. 2014; 9(2):e87133. PMID: 24551051.
      View in: PubMed
    3. Gardai SJ, Mao W, Schüle B, Babcock M, Schoebel S, Lorenzana C, Alexander J, Kim S, Glick H, Hilton K, Fitzgerald JK, Buttini M, Chiou SS, McConlogue L, Anderson JP, Schenk DB, Bard F, Langston JW, Yednock T, Johnston JA. Elevated alpha-synuclein impairs innate immune cell function and provides a potential peripheral biomarker for Parkinson's disease. PLoS One. 2013; 8(8):e71634. PMID: 24058406; PMCID: PMC3751933.
    4. Masliah E, Rockenstein E, Mante M, Crews L, Spencer B, Adame A, Patrick C, Trejo M, Ubhi K, Rohn TT, Mueller-Steiner S, Seubert P, Barbour R, McConlogue L, Buttini M, Games D, Schenk D. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One. 2011 Apr 29; 6(4):e19338. PMID: 21559417; PMCID: PMC3084838.
    5. Inglis KJ, Chereau D, Brigham EF, Chiou SS, Schöbel S, Frigon NL, Yu M, Caccavello RJ, Nelson S, Motter R, Wright S, Chian D, Santiago P, Soriano F, Ramos C, Powell K, Goldstein JM, Babcock M, Yednock T, Bard F, Basi GS, Sham H, Chilcote TJ, McConlogue L, Griswold-Prenner I, Anderson JP. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem. 2009 Jan 30; 284(5):2598-602. PMID: 19004816; PMCID: PMC2631975.
    6. McConlogue L, Buttini M, Anderson JP, Brigham EF, Chen KS, Freedman SB, Games D, Johnson-Wood K, Lee M, Zeller M, Liu W, Motter R, Sinha S. Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP Transgenic Mice. J Biol Chem. 2007 Sep 07; 282(36):26326-34. PMID: 17616527.
      View in: PubMed
    7. Kobayashi D, Zeller M, Cole T, Buttini M, McConlogue L, Sinha S, Freedman S, Morris RG, Chen KS. BACE1 gene deletion: impact on behavioral function in a model of Alzheimer's disease. Neurobiol Aging. 2008 Jun; 29(6):861-73. PMID: 17331621.
      View in: PubMed
    8. Basi G, Frigon N, Barbour R, Doan T, Gordon G, McConlogue L, Sinha S, Zeller M. Antagonistic effects of beta-site amyloid precursor protein-cleaving enzymes 1 and 2 on beta-amyloid peptide production in cells. J Biol Chem. 2003 Aug 22; 278(34):31512-20. PMID: 12801932.
      View in: PubMed
    9. Roberds SL, Anderson J, Basi G, Bienkowski MJ, Branstetter DG, Chen KS, Freedman SB, Frigon NL, Games D, Hu K, Johnson-Wood K, Kappenman KE, Kawabe TT, Kola I, Kuehn R, Lee M, Liu W, Motter R, Nichols NF, Power M, Robertson DW, Schenk D, Schoor M, Shopp GM, Shuck ME, Sinha S, Svensson KA, Tatsuno G, Tintrup H, Wijsman J, Wright S, McConlogue L. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum Mol Genet. 2001 Jun 01; 10(12):1317-24. PMID: 11406613.
      View in: PubMed
    10. Maltese WA, Wilson S, Tan Y, Suomensaari S, Sinha S, Barbour R, McConlogue L. Retention of the Alzheimer's amyloid precursor fragment C99 in the endoplasmic reticulum prevents formation of amyloid beta-peptide. J Biol Chem. 2001 Jun 08; 276(23):20267-79. PMID: 11278337.
      View in: PubMed
    11. 41 Gwen Tatsuno, John Anderson , Jin Hong, David A. Agard, Nobuyuki Ota, Sukanto Sinha, Guriqbal Basi, Lisa McConlogue .Alzheimer’s Disease:Advances in Etiology, Pathogenesis and Therapeutics. Functional analysis of ß-secretase using mutagenesis and structural homology modeling. 2001; Chapter 74:799-808. .
    12. Chen G, Chen KS, Knox J, Inglis J, Bernard A, Martin SJ, Justice A, McConlogue L, Games D, Freedman SB, Morris RG. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature. 2000 Dec 21-28; 408(6815):975-9. PMID: 11140684.
      View in: PubMed
    13. Sinha S, Anderson J, John V, McConlogue L, Basi G, Thorsett E, Schenk D. Recent advances in the understanding of the processing of APP to beta amyloid peptide. Ann N Y Acad Sci. 2000; 920:206-8. PMID: 11193151.
      View in: PubMed
    14. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari SM, Wang S, Walker D, Zhao J, McConlogue L, John V. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999 Dec 02; 402(6761):537-40. PMID: 10591214.
      View in: PubMed
    15. Tan Y, Hong J, Doan T, McConlogue L, Maltese WA. Presenilin-1 mutations associated with familial Alzheimer's disease do not disrupt protein transport from the endoplasmic reticulum to the Golgi apparatus. Biochim Biophys Acta. 1998 Jul 01; 1407(1):69-78. PMID: 9639678.
      View in: PubMed
    16. Gillian AM, McFarlane I, Lucy FM, Overly C, McConlogue L, Breen KC. Individual isoforms of the amyloid beta precursor protein demonstrate differential adhesive potentials to constituents of the extracellular matrix. J Neurosci Res. 1997 Jul 15; 49(2):154-60. PMID: 9272638.
      View in: PubMed
    17. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, Lieberburg I, Schenk D, Seubert P, McConlogue L. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A. 1997 Feb 18; 94(4):1550-5. PMID: 9037091; PMCID: PMC19829.
    18. Zhao J, Paganini L, Mucke L, Gordon M, Refolo L, Carman M, Sinha S, Oltersdorf T, Lieberburg I, McConlogue L. Beta-secretase processing of the beta-amyloid precursor protein in transgenic mice is efficient in neurons but inefficient in astrocytes. J Biol Chem. 1996 Dec 06; 271(49):31407-11. PMID: 8940150.
      View in: PubMed
    19. McConlogue L, Castellano F, deWit C, Schenk D, Maltese WA. Differential effects of a Rab6 mutant on secretory versus amyloidogenic processing of Alzheimer's beta-amyloid precursor protein. J Biol Chem. 1996 Jan 19; 271(3):1343-8. PMID: 8576122.
      View in: PubMed
    20. Rockenstein EM, McConlogue L, Tan H, Power M, Masliah E, Mucke L. Levels and alternative splicing of amyloid beta protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem. 1995 Nov 24; 270(47):28257-67. PMID: 7499323.
      View in: PubMed
    21. Schenk D, Games KD, McConlogue L. The potential utility of transgenic mice harboring beta-amyloid precursor protein. Neurobiol Aging. 1995 Jul-Aug; 16(4):711-3; discussion 715-8. PMID: 8544925.
      View in: PubMed
    22. Dugan JM, deWit C, McConlogue L, Maltese WA. The Ras-related GTP-binding protein, Rab1B, regulates early steps in exocytic transport and processing of beta-amyloid precursor protein. J Biol Chem. 1995 May 05; 270(18):10982-9. PMID: 7738040.
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    23. Knops J, Suomensaari S, Lee M, McConlogue L, Seubert P, Sinha S. Cell-type and amyloid precursor protein-type specific inhibition of A beta release by bafilomycin A1, a selective inhibitor of vacuolar ATPases. J Biol Chem. 1995 Feb 10; 270(6):2419-22. PMID: 7852298.
      View in: PubMed
    24. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. 1995 Feb 09; 373(6514):523-7. PMID: 7845465.
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    25. Kosik KS, McConlogue L. Microtubule-associated protein function: lessons from expression in Spodoptera frugiperda cells. Cell Motil Cytoskeleton. 1994; 28(3):195-8. PMID: 7954847.
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    26. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature. 1992 Dec 17; 360(6405):672-4. PMID: 1465129.
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    27. Overly CC, Fritz LC, Lieberburg I, McConlogue L. The beta-amyloid precursor protein is not processed by the regulated secretory pathway. Biochem Biophys Res Commun. 1991 Dec 16; 181(2):513-9. PMID: 1661581.
      View in: PubMed
    28. Knops J, Kosik KS, Lee G, Pardee JD, Cohen-Gould L, McConlogue L. Overexpression of tau in a nonneuronal cell induces long cellular processes. J Cell Biol. 1991 Aug; 114(4):725-33. PMID: 1678391; PMCID: PMC2289897.
    29. Knops J, Johnson-Wood K, Schenk DB, Sinha S, Lieberburg I, McConlogue L. Isolation of baculovirus-derived secreted and full-length beta-amyloid precursor protein. J Biol Chem. 1991 Apr 15; 266(11):7285-90. PMID: 1901866.
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    30. McConlogue L, Brow MA, Innis MA. Structure-independent DNA amplification by PCR using 7-deaza-2'-deoxyguanosine. Nucleic Acids Res. 1988 Oct 25; 16(20):9869. PMID: 3186456; PMCID: PMC338797.
    31. Chiang TR, McConlogue L. Amplification and expression of heterologous ornithine decarboxylase in Chinese hamster cells. Mol Cell Biol. 1988 Feb; 8(2):764-9. PMID: 3352604; PMCID: PMC363202.
    32. McConlogue L, Dana SL, Coffino P. Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells. Mol Cell Biol. 1986 Aug; 6(8):2865-71. PMID: 3023951; PMCID: PMC367854.
    33. Feinstein SC, Dana SL, McConlogue L, Shooter EM, Coffino P. Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells. Proc Natl Acad Sci U S A. 1985 Sep; 82(17):5761-5. PMID: 3862093; PMCID: PMC390632.
    34. McConlogue L, Gupta M, Wu L, Coffino P. Molecular cloning and expression of the mouse ornithine decarboxylase gene. Proc Natl Acad Sci U S A. 1984 Jan; 81(2):540-4. PMID: 6582509; PMCID: PMC344714.
    35. McConlogue L, Coffino P. A mouse lymphoma cell mutant whose major protein product is ornithine decarboxylase. J Biol Chem. 1983 Oct 25; 258(20):12083-6. PMID: 6415048.
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    36. McConlogue L, Coffino P. Ornithine decarboxylase in difluoromethylornithine-resistant mouse lymphoma cells. Two-dimensional gel analysis of synthesis and turnover. J Biol Chem. 1983 Jul 10; 258(13):8384-8. PMID: 6408089.
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    37. Marcus Pickhardt, Thomas Neumann, Daniel Schwizer, Kari Callaway, Michele Vendruscolo, Dale Schenk, Peter St. George-Hyslop, Eva M. Mandelkow, Christopher M. Dobson, Lisa McConlogue, Eckhard Mandelkow and Gergely Toth.Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies. Current Alzheimer's Research. 12(9):814-828.