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Tali Gidalevitz

Tali Gidalevitz, PhD

Associate Professor
Department of Biology
Office: PISB 418
Phone: 215.571.4219
Lab Location: PISB 410 E
Lab Phone: 215.571.4201


  • Post-Doc, Northwestern University
  • PhD, University of Chicago
  • BS, The Hebrew University of Jerusalem

Research Interests:

Protein misfolding diseases, such as Alzheimer's or Parkinson's diseases, ALS, or certain types of diabetes are becoming increasingly prevalent in the aging human population. Protein misfolding is often implicated in these disorders, but the mechanisms remain unclear. We have shown that misfolding and aggregation of disease-related proteins (e.g. polyglutamine expansions in Huntington's disease, or mutant SOD1 in ALS) can trigger misfolding of other metastable 'bystander' proteins, causing their loss of function and thus disrupting cellular functions. On the other hand, these metastable proteins, encoded by genetic polymorphisms, strongly modulate the disease phenotypes. We proposed that competition for the folding resources underlies this toxic behavior. It is currently thought that understanding such failure of protein homeostasis (proteostasis) is key to understanding and combating aging and neurodegeneration. My lab focuses on mechanisms that control proteostasis, using genetic, biochemical, and live imaging approaches in a metazoan C. elegans and mammalian neurons. We currently have three main research directions:

1. The mechanism of differential neuronal susceptibility to protein misfolding. A. Why only some neurons are affected in disease, when the toxic protein is often expressed in all or many neurons? We are using C. elegans to ask whether dysfunction of the susceptible neuron can be explained by misfolding of a 'bystander' protein that is not present in other neurons, and what makes a particular 'bystander' protein a risk factor for a given neuron. B. An exciting new direction that sprung from the above work is the finding that a folding stress in the ER of neurons derails the correct targeting of neurotrophic secreted molecules to axons or dendrites. We are examining the novel function of an ER stress sensor, PERK, in regulating the axonal/dendritic targeting, and whether it explains why mutations in PERK are a risk factor for Alzheimer's disease and tauopathy.

2. The role of natural genetic variation and physiological stress in proteostasis. A. We are using wild strains of C. elegans to understand 1) what is the nature of polymorphisms and genetic networks that control susceptibility of cells to protein aggregation and toxicity, and 2) how natural variation controls resistance to vs. tolerance of aggregation. B. We are harnessing the natural, evolutionarily selected mechanisms that protect proteostasis. For example, we have identified a small heat-shock protein HSP-12.6 as a major defender of proteostasis in the stress-resistant dauer larva, and are testing its mechanism of action.

3. Maintaining the ER proteostasis under physiological stress. A. We are studying how cells match which ER chaperones are induced during differentiation to their future protein folding needs, since different secreted proteins will need different chaperones for their efficient folding. B. In collaboration with Dr. Argon's lab (CHOP) we are studying the regulation of an ER stress sensor IRE1 in adaptation to changes in ER proteostasis, and in collaboration with both Dr. Argon's and Dr. Behtea's labs – the possibility of manipulating the IRE1 activity to improve re-myelination in a Multiple Sclerosis model.

Selected Publications:

  • Zha J, Alexander-Floyd J, Gidalevitz T*. (2018) HSP-4/BiP expression in secretory cells is regulated by a lineage-dependent differentiation program and not by the unfolded protein response. bioRxiv 388272; doi:
  • Haroon S, Li A, Weinert JL, Fritsch C, Ericson N, Alexander-Floyd J, Braeckman BP, Haynes C, Bielas J, Gidalevitz T, Vermulst M. (2018) Multiple molecular mechanisms rescue mtDNA disease in C. elegans. Cell Reports 22(12):3115-3125, PMID: 29562168
  • Klabonski L, Zha J, Senthilkumar L, Gidalevitz T*. (2016) A bystander mechanism explains the specific phenotype of a broadly expressed misfolded protein. PLoS Genetics 12, e1006450, PMID: 27926939
    Commentary on this article:
    -Ruvinsky I: F1000Prime Recommendation. F1000Prime, 02 Feb 2017
  • Eletto D, Eletto D, Dersh D, Gidalevitz T*, Argon Y*. (2014) Protein Disulfide Isomerase A6 controls the decay of IRE1α signaling via disulfide-dependent association. Molecular Cell 53, 562-76, PMID: 24508390
  • Gidalevitz T*, Wang N, Deravaj T, Alexander-Floyd J, Morimoto RI (2013) Natural genetic variation determines susceptibility to aggregation or toxicity in a C. elegans model for polyglutamine disease. BMC Biology 11: 100, PMID: 24079614
    Commentary on this article:
    -Matt Kaeberlein. (2013) Deciphering the role of natural variation in age-related protein homeostasis. BMC Biology 11:102
  • Gidalevitz T, Stevens F, Argon Y. (2013) Orchestration of secretory protein folding by ER chaperones. Biochim Biophys Acta. 1833, 2410-24. PMID: 23507200
  • Gidalevitz T, Krupinski T, Garcia S, Morimoto RI. (2009) Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLOS Genetics. 5(3):e1000399 PMID: 19266020
  • Gidalevitz T#, Ben-Zvi A#, Ho KH, Brignull HR, Morimoto RI. (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311(5766):1471 – 1474 PMID: 16469881
    # - equal contribution
    Commentary on this article:
    -Faculty of 1000 evaluation: Must Read
    -Alzforum: Protein Aggregation In Disease - A New Theory Joins the Fold
    -Bates GP. (2006) One Misfolded Protein Allows Others to Sneak By. Science. 311(5766):1385-6
    -Williams R. (2006) Neurodegenerative diseases: Folding failure. Research Highlight. Nature Reviews Neuroscience 7, 252