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, 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.
    View on 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.
    View on 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.
    View on PubMed
  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.
    View on PubMed
  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.
    View on PubMed
  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.
    View on 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.
    View on 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.
    View on 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.
    View on 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.
    View on 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. .
    View on PubMed
  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.
    View on 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.
    View on 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.
    View on 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.
    View on 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.
    View on 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.
    View on PubMed
  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.
    View on 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.
    View on 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.
    View on PubMed

Go to UCSF Profiles, powered by CTSI