Prof. Gerardo Lederkremer

Prof. Gerardo Lederkremer

Research work

Our lab focuses on the mechanisms of protein folding and trafficking in the early secretory pathway of mammalian cells, with special focus on endoplasmic reticulum protein quality control, delivery of misfolded proteins to ER-associated degradation and the genesis of ER stress. The Lederkremer lab is one of the leading research groups worldwide in these areas, and has produced seminal findings. In recent years the lab has investigated the generation of ER stress in neurodegenerative diseases, which leads to cytotoxicity and neurodegeneration. The lab’s research on cellular and mouse models of Huntington’s disease has led to the discovery of a promising therapeutic approach to the disease, intervening with the pathways of the unfolded protein response.


Areas of interest & scientific knowledge

Brain Disorders Research

Cellular & Molecular Neuroscience

Selected Publications
  • LGanz J, Shacham T, Kramer M, Shenkman M, Eiger H, Weinberg N, Iancovici O, Roy S, Simhaev L, Da'adoosh B, Engel H, Perets N, Barhum Y, Portnoy M, Offen D, Lederkremer GZ.  A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models Sci Rep. 2020 Apr 23;10(1):6875. doi: 10.1038/s41598-020-63899-4.
  • García-Huerta P, Troncoso-Escudero P, Wu D, Thiruvalluvan A, Cisternas-Olmedo M, Henríquez DR, Plate L, Chana-Cuevas P, Saquel C, Thielen P, Longo KA, Geddes BJ, Lederkremer GZ, Sharma N, Shenkman M, Naphade S, Sardi SP, Spichiger C, Richter HG, Court FA, Tshilenge KT, Ellerby LM, Wiseman RL, Gonzalez-Billault C, Bergink S,
    Vidal RL, HetzC. Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracellular disposal of protein aggregates Acta Neuropathol. 2020 Jul 8. doi: 10.1007/s00401-020-02183-1.
  • Ogen-Shtern N, Ben David T, Lederkremer GZ. Protein aggregation and ER stress Brain Res. 2016 Oct 1;1648(Pt B):658-666. doi: 10.1016/j.brainres.2016.03.044.
  • Leitman J, Barak B, Benyair R, Shenkman M, Ashery U, Hartl FU, Lederkremer GZ. ER stress-induced eIF2-alpha phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin PLoS One. 2014 Mar 3;9(3):e90803. doi: 10.1371/journal.pone.0090803.
  • Leitman J, Ulrich Hartl F, Lederkremer GZ. Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress Nat Commun. 2013;4:2753. doi: 10.1038/ncomms3753.
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