Header Logo

Donald John Tipper PhD

TitleProfessor Emeritus
InstitutionUMass Chan Medical School
DepartmentMicrobiology and Physiological Systems
AddressUMass Chan Medical School
55 Lake Avenue North S6-228
Worcester MA 01655
vCardDownload vCard
    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionUMass Chan Programs, Centers and Institutes
    DepartmentBacterial Genetics and Pathogenesis

    Collapse Biography 
    Collapse education and training
    University of Birmingham, Birmingham, , United KingdomBSCChemistry
    University of Birmingham, Birmingham, , United KingdomPHDChemistry

    Collapse Overview 
    Collapse overview

    Academic Background

    Ph. D. (1959) University of Birmingham (UK)

    Yeast Molecular Genetics

    The relationship between prion protein sequence and disease. Use of yeast as a model system for analysis of determinants of their transmembrane topology.

    Photo: Donald J. TipperMy laboratory uses yeast for the molecular genetic analysis of determinants of transmembrane (TM) protein topology. Both prion diseases and far more prevalent diseases such as Alzheimer's and cystic fibrosis result from errors in folding, membrane insertion, localization or processing of TM proteins. Although the topogenic signals that determine the topology of insertion are quite well understood (and have been extensively studied in yeast by my lab), the mechanisms for response to these signals are unknown. A long term goal is to characterize these mechanisms by the analysis of yeast mutants defective in responses to these signals. Our primary focus, however, is to use these techniques to analyze the relationship between mutations in the mammalian prion protein (PrP), membrane insertion and pathogenesis.

    Misfolded forms of PrP appear to be both the infectious agent of prion diseases and the primary cause of the neurotoxicity that leads to slowly lethal destruction of the brain. About 10% of human prion disease are familial, caused by mutations in the PrP gene. Recent studies show that, in at least one class of such mutants, neurotoxicity correlates with increased production of a normally rare transmembrane (TM) form of PrP, called PrPCtm, that may be the actual toxic form in all prion disease. We have shown that yeast is an efficient system for analysis of the relationship between pathogenic PrP mutations and TM topology. Using PrP as a model, we are collaborating in analysis of a previously unidentified component of the mammalian protein translocation apparatus that helps to control the topology of insertion of PrP and, presumably, other translocated proteins.

    Collapse Rotation Projects

    Rotation Projects

    1. Determine the mechanism of PrPCtm production by constructing PrP mutants with N-terminal glycosylation sites and analyzing their modification in yeast and in vitro.

    2. Test the role of PrPCtm in prion pathology by determining the effects of changing the charged topogenic signals in PrP on transmembrane insertion and pathogenicity.

    3. Isolate new pio mutants and determine their effects on normal yeast TM proteins.

    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. Tipper DJ, Harley CA. Spf1 and Ste24: quality controllers of transmembrane protein topology in the eukaryotic cell. Front Cell Dev Biol. 2023; 11:1220441. PMID: 37635876.
    2. Tipper DJ, Szomolanyi-Tsuda E. Scaffolded Antigens in Yeast Cell Particle Vaccines Provide Protection against Systemic Polyoma Virus Infection. J Immunol Res. 2016; 2016:2743292. PMID: 27213160.
      Citations: 4     Fields:    Translation:AnimalsCellsPHPublic Health
    3. Specht CA, Lee CK, Huang H, Tipper DJ, Shen ZT, Lodge JK, Leszyk J, Ostroff GR, Levitz SM. Protection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing Cryptococcus Alkaline Extracts. mBio. 2015 Dec 22; 6(6):e01905-15. PMID: 26695631.
      Citations: 42     Fields:    Translation:AnimalsCellsPHPublic Health
    4. Tipper D, Martinez-Vilchez I, Markgren L, Kagalwala DZ. Mammalian Prion protein expression in yeast; a model for transmembrane insertion. Prion. 2013 Nov-Dec; 7(6):477-87. PMID: 24141197.
      Citations: 1     Fields:    Translation:AnimalsCells
    5. Campellone KG, Brady MJ, Alamares JG, Rowe DC, Skehan BM, Tipper DJ, Leong JM. Enterohaemorrhagic Escherichia coli Tir requires a C-terminal 12-residue peptide to initiate EspF-mediated actin assembly and harbours N-terminal sequences that influence pedestal length. Cell Microbiol. 2006 Sep; 8(9):1488-503. PMID: 16922867.
      Citations: 21     Fields:    Translation:HumansCells
    6. Biswas S, Langeveld JP, Tipper D, Lu S. Intracellular accumulation of a 46 kDa species of mouse prion protein as a result of loss of glycosylation in cultured mammalian cells. Biochem Biophys Res Commun. 2006 Oct 13; 349(1):153-61. PMID: 16935263.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    7. Campellone KG, Rankin S, Pawson T, Kirschner MW, Tipper DJ, Leong JM. Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to trigger localized actin assembly. J Cell Biol. 2004 Feb 02; 164(3):407-16. PMID: 14757753.
      Citations: 56     Fields:    Translation:HumansAnimalsCells
    8. Tipper DJ, Harley CA. Yeast genes controlling responses to topogenic signals in a model transmembrane protein. Mol Biol Cell. 2002 Apr; 13(4):1158-74. PMID: 11950929.
      Citations: 29     Fields:    Translation:AnimalsCells
    9. Campellone KG, Giese A, Tipper DJ, Leong JM. A tyrosine-phosphorylated 12-amino-acid sequence of enteropathogenic Escherichia coli Tir binds the host adaptor protein Nck and is required for Nck localization to actin pedestals. Mol Microbiol. 2002 Mar; 43(5):1227-41. PMID: 11918809.
      Citations: 70     Fields:    Translation:Cells
    10. Breinig F, Tipper DJ, Schmitt MJ. Kre1p, the plasma membrane receptor for the yeast K1 viral toxin. Cell. 2002 Feb 08; 108(3):395-405. PMID: 11853673.
      Citations: 37     Fields:    Translation:Animals
    Tipper's Networks
    Click the
    buttons for more information and interactive visualizations!
    Concepts (110)
    Co-Authors (5)
    Similar People (60)
    Same Department Expand Description
    Physical Neighbors