University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Lisa McConlogue, PhD

Lisa McConlogue, PhD

Adjunct Professor of Biochemistry and Biophysics, UCSF

Cancer Center Program Memberships

Experimental Therapeutics

Research Summary

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.

Education

University of California, Los Angeles, B.A., 1973, Mathematics
University of California, Los Angeles, M.S., 1975, Medical Physics
University of California, Los Angeles, Ph.D., 1978, Medical Physics
University of California, San Francisco, Postdoctoral, 1985, Somatic Cell Genetics


Professional Experience

  • 2015-present
    Visiting Investigator, Gladstone Institute of Neurological Disease (GIND)
  • 2014-present
    Adjunct Professor of Biochemistry and Biophysics, UCSF
  • 2012-2013
    Distinguished Research Fellow, Elan Pharmaceuticals (Vice President level research position) Steering Committee, Cambridge Elan Centre for Research Excellence and Drug Discovery, Cambridge Elan Alliance project leader.
  • 2010-2012
    Research Fellow, Parkinson’s Disease Strategic and Synuclein Stabilization Project leader, Elan.
  • 2006-2011
    Research Fellow, Group Leader of Molecular Genetics, Parkinson’s Disease Project Leader, Elan
  • 2002-2006
    Senior Scientist, Group Leader of Molecular Genetics, Parkinson’s Disease Discovery Project Leader. Elan Pharmaceuticals
  • 2000-2002
    Senior Scientist, Group Leader of Molecular Biology, Project leader, Digital Gene Technologies/Elan AD Joint Venture, Elan Pharmaceuticals
  • 1998-2000
    Principal Scientist, Group Leader of Molecular Biology Elan Pharmaceuticals
  • 1997-1998
    Staff Scientist, Group Leader of Molecular Biology, Elan Pharmaceuticals
  • 1993-1997
    Staff Scientist, Associate Director of Molecular Biology, Project Leader Dyax/Elan phage display collaboration. Athena Neurosciences
  • 1988-1992
    Scientist, Molecular Biology, Athena Neurosciences
  • 1985-1988
    Scientist, Molecular Biology, Project Manager Mammalian Expression, Cetus Corporation

Selected Publications

  1. Pickhardt M, Neumann T, Schwizer D, Callaway K, Vendruscolo M, Schenk D, George-Hyslop PS, Mandelkow EM, Dobson CM, McConlogue L, Mandelkow E, Toth 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.
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  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.
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  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.
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  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; 6(4):e19338.
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  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.
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  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 7; 282(36):26326-34.
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  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.
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  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.
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  9. Wyss-Coray T, McConlogue L, Kindy M, Schmidt AM, Du Yan S, Stern DM. Key signaling pathways regulate the biological activities and accumulation of amyloid-beta. Neurobiol Aging. 2001 Nov-Dec; 22(6):967-73.
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  10. 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 1; 10(12):1317-24.
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  11. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, Masliah E, Mucke L. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med. 2001 May; 7(5):612-8.
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  12. 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 8; 276(23):20267-79.
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  13. 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. .
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  14. Mucke L, Yu GQ, McConlogue L, Rockenstein EM, Abraham CR, Masliah E. Astroglial expression of human alpha(1)-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice. Am J Pathol. 2000 Dec; 157(6):2003-10.
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  15. 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.
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  16. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000 Jun 1; 20(11):4050-8.
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  17. 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.
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  18. 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 2; 402(6761):537-40.
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  19. Huang F, Buttini M, Wyss-Coray T, McConlogue L, Kodama T, Pitas RE, Mucke L. Elimination of the class A scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors. Am J Pathol. 1999 Nov; 155(5):1741-7.
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  20. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci U S A. 1999 Mar 16; 96(6):3228-33.
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