Prof. Gerardo Lederkremer

Molecular Cell Biology and Bio
Medicine Dean & Assoc. Deans
ביולוגיה מולקולרית של התא ולב סגל אקדמי בכיר
Prof. Gerardo Lederkremer
Phone: 03-6409239
Another phone: 03-6407610
Fax: 03-6422046
Office: Britannia-Porter, 320



Gerardo Lederkremer researches cell biology processes in the early secretory pathway of mammalian cells and teaches courses on cell biology and glycobiology. He grew up in Buenos Aires, Argentina where he studied and received his PhD at the University of Buenos Aires under the supervision of Armando Parodi. After postdoctoral training with Harvey Lodish at the Whitehead Institute for Biomedical Research, MIT, he immigrated to Israel in 1991 and since then has been a faculty member at Tel Aviv University. He was a visiting scientist at Harvard Medical School (1999-2000) and at Boston Children’s Hospital (2013).


Research Interests


Prof. Lederkremer’s lab has been interested in the mechanisms of protein folding and trafficking in the early secretory pathway of mammalian cells. He has focused especially on mechanisms of ER quality control of protein folding and on recognition and delivery of misfolded proteins from the ER to the cytosolic proteasomes for ERAD. These processes are intimately linked to the genesis of ER stress in disease, which he has also been studying. Recent research of the lab on cellular and mouse models of Huntington’s disease has led to the discovery of a promising therapeutic approach to the disease, boosting the unfolded protein response.  


Specific research topics are:
• Protein misfolding diseases, focusing on neurodegenerative diseases, especially Huntington’s disease.
• ER stress.
• Mechanisms of endoplasmic reticulum (ER) protein folding and quality control.
• Sugar chain trimming processes as cellular signals for glycoprotein folding status.
• Delivery of misfolded proteins to ER-associated degradation (ERAD).
• Subcellular compartmentalization of ER quality control and ERAD. 
His research in these areas has led to important discoveries. One of them is the identification of a novel subcellular compartment involved in these processes, as a staging ground for ERAD. The second is a process that modifies specifically the sugar chains of misfolded glycoproteins after refolding attempts have failed, creating a signal for delivery to ERAD. These processes are regulated by ER stress and the consequent unfolded protein response (UPR) and he has established that the compartmentalization and assembly of a molecular complex that targets to ERAD are dependent on one of the branches of the UPR. His group has found that interference with ERAD and upregulation of the UPR are a main mechanism of cell damage in a neurodegenerative disorder, Huntington’s disease, and that this occurs prior to the appearance of the characteristic large protein inclusions that occur in this disease. Application of this knowledge has led his lab to develop small molecule boosters of one of the pathways of the UPR, with promising therapeutic potential in neurodegenerative disease.  

Recent Publications



For the complete list, visit his lab website:


Sharma N, Patel C, Shenkman M, Kessel A, Ben-Tal N, Lederkremer GZ. The Sigma-1 receptor is an ER-localized type II membrane protein. J Biol Chem. 2021 Oct 11;297(5):101299.


Shenkman M, Geva M, Gershoni-Emek N, Hayden MR, Lederkremer GZ.  Pridopidine reduces mutant huntingtin-induced endoplasmic reticulum stress by modulation of the Sigma-1 receptor. J Neurochem. 2021 Jul;158(2):467-481.


Shacham T, Patel C, Lederkremer GZ. PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate? Biomolecules. 2021 Feb 26;11(3):354.


Patel C, Saad H, Shenkman M, Lederkremer GZ. Oxidoreductases in Glycoprotein Glycosylation, Folding, and ERAD. Cells. 2020 Sep 22;9(9):2138. doi: 10.3390/cells9092138.


Ganz 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. 10(1):6875. doi: 10.1038/s41598-020-63899-4. (2020)


Saad, H., Patel, C., Lederkremer, G.Z. (2019) Letting go of O-glycans. J.Biol.Chem. 294, 15912-3.


Shacham, T., Sharma, N. and Lederkremer GZ. Protein misfolding and ER stress in Huntington’s disease. Front Mol Biosci. 6:20. doi: 10.3389/fmolb.2019.00020. (2019).


Shenkman, M., and Lederkremer, G. Z. (2019)

Compartmentalization and Selective Tagging for Disposal of Misfolded Glycoproteins.

Trends in biochemical sciences 44, 827-836


Shenkman M, Ron E, Yehuda R, Benyair R, Khalaila I and Lederkremer GZ. (2018). Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates. Commun Biol. 1:172.


Ogen-Shtern, N., Ben-David, T. and Lederkremer, GZ. (2016). Protein Aggregation and ER Stress. Brain Res. 1648, 658-666.


Ogen-Shtern, N., Avezov, E., Shenkman, M., Benyair, R. and Lederkremer, GZ. (2016). Mannosidase IA is in quality control vesicles and participates in glycoprotein targeting to ERAD. J Mol Biol 428, 3194-205.

Benyair, R., Ogen-Shtern, N., Mazkereth, N., Shai, B., Ehrlich, M. and Lederkremer, G.Z. (2015). Mammalian ER mannosidase I resides in quality control vesicles where it encounters its glycoprotein substrates. Mol Biol Cell 26, 172-84.


Benyair, R., Ogen-Shtern, N. and Lederkremer, GZ. (2015). Glycan regulation of ER-associated degradation through compartmentalization. Seminars Cell Dev Biol 41:99-109.


Leitman, J., Barak, B., Benyair, R., Shenkman, M., Ashery, U., Hartl, F.U. and Lederkremer, G.Z. ER Stress-induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin. PLoS One 2014  9(3): e90803. pp. 1-10. 


Leitman, J., Shenkman, M., Gofman, Y., Ben-Tal, N., Hendershot, L.M. and Lederkremer, G.Z. Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD. Mol Biol Cell. 2014 25(7):1050-60.


Leitman, J., Hartl, F.U. and Lederkremer, G.Z. Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress. Nature Commun 2013;4:2753. pp. 1-10.



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