Lisa Sharkey, PhD
Research Assistant Professor, Neurology
[email protected]

Available to mentor
Lisa Sharkey, PhD
Research Assistant Professor
  • Research Overview
  • Recent Publications
    • Research Overview

    • My research program is focused on understanding the molecular mechanisms and physiological consequences of protein mis-folding in neurodegenerative disease. I study a family of brain-expressed ubiquitin adaptor proteins, the ubiquilins (UBQLN1, 2 and 4), that help maintain neuronal protein homeostasis. The overarching goals of my research are to determine: 1) how disease mutations in UBQLN2 alter its liquid-liquid-phase separation (LLPS) behavior and contribute to neurotoxicity 2) under what conditions UBQLN2, normally a cytoplasmic protein, translocates to the nucleus and what role it plays there and 3) why we have three highly homologous UBQLNs expressed in the brain and what homologue-specific roles they play in health and disease.
    • Ubiquilins; ALS/FTD; neurodegenerative disease; liquid-liquid-phase-separation; aging and protein quality control

    Recent Publications See All Publications
    • Journal Article
      Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity.
      Safren N, Dao TP, Mohan HM, Huang C, Trotter B, Castañeda CA, Paulson H, Barmada S, Sharkey LM. Sci Rep, 2024 Mar 13; 14 (1): 6049 DOI:10.1038/s41598-024-55582-9
      PMID: 38472280
    • Journal Article
      Upregulation of the ESCRT pathway and multivesicular bodies accelerates degradation of proteins associated with neurodegeneration.
      Benyair R, Giridharan SSP, Rivero-Ríos P, Hasegawa J, Bristow E, Eskelinen E-L, Shmueli MD, Fishbain-Yoskovitz V, Merbl Y, Sharkey LM, Paulson HL, Hanson PI, Patnaik S, Al-Ramahi I, Botas J, Marugan J, Weisman LS. Autophagy Rep, 2023 2 (1): DOI:10.1080/27694127.2023.2166722
      PMID: 37064812
    • Presentation
      From Mutations to Mechanisms: UBQLN2's Role in Protein Quality Control and Neurodegenerative Disease
      Sharkey L. 2023 Dec 5;
    • Journal Article
      Ubiquilin-2 regulates pathological alpha-synuclein.
      Sandoval-Pistorius SS, Gerson JE, Liggans N, Ryou JH, Oak K, Li X, Negron-Rios KY, Fischer S, Barsh H, Crowley EV, Skinner ME, Sharkey LM, Barmada SJ, Paulson HL. Sci Rep, 2023 Jan 6; 13 (1): 293 DOI:10.1038/s41598-022-26899-0
      PMID: 36609661
    • Journal Article
      Flow cytometric isolation of drug-like conformational antibodies specific for amyloid fibrils.
      Desai AA, Zupancic JM, Trzeciakiewicz H, Gerson JE, DuBois KN, Skinner ME, Sharkey LM, McArthur N, Ferris SP, Bhatt NN, Makowski EK, Smith MD, Chen H, Huang J, Jerez C, Kane RS, Kanaan NM, Paulson HL, Tessier PM. bioRxiv, 2023 Jul 4; DOI:10.1101/2023.07.04.547698
      PMID: 37461643
    • Journal Article
      Wild-type and pathogenic forms of ubiquilin 2 differentially modulate components of the autophagy-lysosome pathways.
      Idera A, Sharkey LM, Kurauchi Y, Kadoyama K, Paulson HL, Katsuki H, Seki T. J Pharmacol Sci, 2023 Jul; 152 (3): 182 - 192. DOI:10.1016/j.jphs.2023.05.002
      PMID: 37257946
    • Presentation
      Uncovering critical roles for retrotransposon-derived proteins in Ubiquilin-2 (UBQLN2) biology; implications for ALS research
      Sharkey L. 2023 May 12;
    • Presentation
      Ubiquilin2’s role in neuronal protein quality control pathways
      Sharkey L. 2023 May 3;