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Jill A Zitzewitz PhD

TitleAssociate Professor
InstitutionUMass Chan Medical School
AddressUMass Chan Medical School
364 Plantation Street LRB
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionT.H. Chan School of Medicine
    DivisionTranslational Anatomy

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionMorningside Graduate School of Biomedical Sciences

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science

    Collapse Biography 
    Collapse education and training
    Carthage College, Kenosha, WI, United StatesBAChemistry
    Washington State University, Pullman, WA, United StatesPHDBioorganic Chemistry

    Collapse Overview 
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    Protein Misfolding and Disease

    The overall goal of our research program is to probe the folding of ALS-linked proteins in order to provide a molecular level understanding of how misfolding contributes to disease.  A thermodynamic analysis of the molecular interactions stabilizing the native, functional conformation is a key first step to the development of small molecule screening assays for identifying therapeutic compounds that prevent misfolding.  Current research efforts focus on utilizing biophysical methods to probe the folding, misfolding and aberrant aggregation processes in ALS variants of SOD1 and TDP-43.  It is our expectation that these studies will not only lead to new insights into how to prevent misfolding in a set of human diseases, they will also provide guidelines for the biotechnological development of therapeutic small molecules and antibodies to treat disease.

    Academic Background

    Jill Zitzewitz received her B.A. in Chemistry from Carthage College in 1986 and her PhD in Bioorganic Chemistry from Washington University in St. Louis in 1991.  She completed postdoctoral training in protein folding at The Pennsylvania State University, where she was awarded an NIH fellowship.  Jill joined the faculty of Biochemistry and Molecular Pharmacology at UMass Medical School in 2001.

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Niu B, Mackness BC, Zitzewitz JA, Matthews CR, Gross ML. Trifluoroethanol Partially Unfolds G93A SOD1 Leading to Protein Aggregation: A Study by Native Mass Spectrometry and FPOP Protein Footprinting. Biochemistry. 2020 10 06; 59(39):3650-3659. PMID: 32924445.
      Citations: 3     Fields:    Translation:HumansCells
    2. Cohen NR, Kayatekin C, Zitzewitz JA, Bilsel O, Matthews CR. Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1. Biophys J. 2020 04 21; 118(8):1992-2000. PMID: 32191862.
      Citations: 2     Fields:    Translation:HumansCells
    3. Cohen NR, Zitzewitz JA, Bilsel O, Matthews CR. Nonnative structure in a peptide model of the unfolded state of superoxide dismutase 1 (SOD1): Implications for ALS-linked aggregation. J Biol Chem. 2019 09 13; 294(37):13708-13717. PMID: 31341015.
      Citations: 2     Fields:    Translation:HumansCells
    4. Tavella D, Zitzewitz JA, Massi F. Characterization of TDP-43 RRM2 Partially Folded States and Their Significance to ALS Pathogenesis. Biophys J. 2018 11 06; 115(9):1673-1680. PMID: 30309612.
      Citations: 8     Fields:    Translation:HumansCells
    5. Morgan BR, Zitzewitz JA, Massi F. Structural Rearrangement upon Fragmentation of the Stability Core of the ALS-Linked Protein TDP-43. Biophys J. 2017 Aug 08; 113(3):540-549. PMID: 28793209.
      Citations: 1     Fields:    Translation:HumansCells
    6. Niu B, Mackness BC, Rempel DL, Zhang H, Cui W, Matthews CR, Zitzewitz JA, Gross ML. Incorporation of a Reporter Peptide in FPOP Compensates for Adventitious Scavengers and Permits Time-Dependent Measurements. J Am Soc Mass Spectrom. 2017 02; 28(2):389-392. PMID: 27924496.
      Citations: 20     Fields:    Translation:Cells
    7. Boopathy S, Silvas TV, Tischbein M, Jansen S, Shandilya SM, Zitzewitz JA, Landers JE, Goode BL, Schiffer CA, Bosco DA. Structural basis for mutation-induced destabilization of profilin 1 in ALS. Proc Natl Acad Sci U S A. 2015 Jun 30; 112(26):7984-9. PMID: 26056300.
      Citations: 37     Fields:    Translation:HumansCells
    8. Mackness BC, Tran MT, McClain SP, Matthews CR, Zitzewitz JA. Folding of the RNA recognition motif (RRM) domains of the amyotrophic lateral sclerosis (ALS)-linked protein TDP-43 reveals an intermediate state. J Biol Chem. 2014 Mar 21; 289(12):8264-76. PMID: 24497641.
      Citations: 20     Fields:    Translation:HumansCells
    9. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23; 488(7412):499-503. PMID: 22801503.
      Citations: 288     Fields:    Translation:HumansAnimalsCells
    10. Svensson AK, Bilsel O, Kayatekin C, Adefusika JA, Zitzewitz JA, Matthews CR. Metal-free ALS variants of dimeric human Cu,Zn-superoxide dismutase have enhanced populations of monomeric species. PLoS One. 2010 Apr 09; 5(4):e10064. PMID: 20404910.
      Citations: 25     Fields:    Translation:HumansCells
    11. Kayatekin C, Zitzewitz JA, Matthews CR. Disulfide-reduced ALS variants of Cu, Zn superoxide dismutase exhibit increased populations of unfolded species. J Mol Biol. 2010 Apr 30; 398(2):320-31. PMID: 20184893.
      Citations: 26     Fields:    Translation:HumansCells
    12. Noel AF, Bilsel O, Kundu A, Wu Y, Zitzewitz JA, Matthews CR. The folding free-energy surface of HIV-1 protease: insights into the thermodynamic basis for resistance to inhibitors. J Mol Biol. 2009 Apr 10; 387(4):1002-16. PMID: 19150359.
      Citations: 14     Fields:    Translation:Cells
    13. Kayatekin C, Zitzewitz JA, Matthews CR. Zinc binding modulates the entire folding free energy surface of human Cu,Zn superoxide dismutase. J Mol Biol. 2008 Dec 12; 384(2):540-55. PMID: 18840448.
      Citations: 33     Fields:    Translation:HumansCells
    14. Gu Z, Zitzewitz JA, Matthews CR. Mapping the structure of folding cores in TIM barrel proteins by hydrogen exchange mass spectrometry: the roles of motif and sequence for the indole-3-glycerol phosphate synthase from Sulfolobus solfataricus. J Mol Biol. 2007 Apr 27; 368(2):582-94. PMID: 17359995.
      Citations: 22     Fields:    Translation:Cells
    15. Svensson AK, Bilsel O, Kondrashkina E, Zitzewitz JA, Matthews CR. Mapping the folding free energy surface for metal-free human Cu,Zn superoxide dismutase. J Mol Biol. 2006 Dec 15; 364(5):1084-102. PMID: 17046019.
      Citations: 33     Fields:    Translation:HumansCells
    16. Svensson AK, Zitzewitz JA, Matthews CR, Smith VF. The relationship between chain connectivity and domain stability in the equilibrium and kinetic folding mechanisms of dihydrofolate reductase from E.coli. Protein Eng Des Sel. 2006 Apr; 19(4):175-85. PMID: 16452118.
      Citations: 6     Fields:    Translation:Cells
    17. Ibarra-Molero B, Zitzewitz JA, Matthews CR. Salt-bridges can stabilize but do not accelerate the folding of the homodimeric coiled-coil peptide GCN4-p1. J Mol Biol. 2004 Mar 05; 336(5):989-96. PMID: 15037063.
      Citations: 18     Fields:    Translation:Cells
    18. Knappenberger JA, Smith JE, Thorpe SH, Zitzewitz JA, Matthews CR. A buried polar residue in the hydrophobic interface of the coiled-coil peptide, GCN4-p1, plays a thermodynamic, not a kinetic role in folding. J Mol Biol. 2002 Aug 02; 321(1):1-6. PMID: 12139928.
      Citations: 11     Fields:    Translation:Cells
    19. Zitzewitz JA, Ibarra-Molero B, Fishel DR, Terry KL, Matthews CR. Preformed secondary structure drives the association reaction of GCN4-p1, a model coiled-coil system. J Mol Biol. 2000 Mar 03; 296(4):1105-16. PMID: 10686107.
      Citations: 37     Fields:    Translation:Cells
    20. Gualfetti PJ, Iwakura M, Lee JC, Kihara H, Bilsel O, Zitzewitz JA, Matthews CR. Apparent radii of the native, stable intermediates and unfolded conformers of the alpha-subunit of tryptophan synthase from E. coli, a TIM barrel protein. Biochemistry. 1999 Oct 05; 38(40):13367-78. PMID: 10529212.
      Citations: 10     Fields:    Translation:Cells
    21. Zitzewitz JA, Matthews CR. Molecular dissection of the folding mechanism of the alpha subunit of tryptophan synthase: an amino-terminal autonomous folding unit controls several rate-limiting steps in the folding of a single domain protein. Biochemistry. 1999 Aug 03; 38(31):10205-14. PMID: 10433729.
      Citations: 6     Fields:    Translation:Cells
    22. Zitzewitz JA, Gualfetti PJ, Perkons IA, Wasta SA, Matthews CR. Identifying the structural boundaries of independent folding domains in the alpha subunit of tryptophan synthase, a beta/alpha barrel protein. Protein Sci. 1999 Jun; 8(6):1200-9. PMID: 10386870.
      Citations: 16     Fields:    Translation:Cells
    23. Bilsel O, Yang L, Zitzewitz JA, Beechem JM, Matthews CR. Time-resolved fluorescence anisotropy study of the refolding reaction of the alpha-subunit of tryptophan synthase reveals nonmonotonic behavior of the rotational correlation time. Biochemistry. 1999 Mar 30; 38(13):4177-87. PMID: 10194334.
      Citations: 7     Fields:    Translation:Cells
    24. Bilsel O, Zitzewitz JA, Bowers KE, Matthews CR. Folding mechanism of the alpha-subunit of tryptophan synthase, an alpha/beta barrel protein: global analysis highlights the interconversion of multiple native, intermediate, and unfolded forms through parallel channels. Biochemistry. 1999 Jan 19; 38(3):1018-29. PMID: 9893998.
      Citations: 46     Fields:    Translation:Cells
    25. Zitzewitz JA, Bilsel O, Luo J, Jones BE, Matthews CR. Probing the folding mechanism of a leucine zipper peptide by stopped-flow circular dichroism spectroscopy. Biochemistry. 1995 Oct 03; 34(39):12812-9. PMID: 7548036.
      Citations: 54     Fields:    Translation:Cells
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