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Theo (T.) Rispens PhD

Structure & function of antibodies

Training

Physical and organic chemistry

Thesis

'Cycloadditions in weakly and highly organized aqueous media. Kinetic studies of cycloadditions in aqueous solvent mixtures and surfactant solutions'

Research interests

Structure and function of human immunoglobulins are key players in immune responses against many pathogens, but also against non-infectious agents such as allergens or therapeutic biomolecules. Depending on the type of antibody, its effects may range from immune activation, target neutralization, to down-modulation of the immune response. It is only partially understood how the many functions of immunoglobulins relate to their structural variability (including subclass, glycosylation profile, hinge isomers). In a therapeutic setting, antibodies are used to treat a variety of disorders. Stability and composition are major factors that influence efficacy and may lead to adverse effects such as hypersensitivity reactions. For monoclonal antibodies, immunogenicity is increasingly being recognized as a potential threat. Our main theme is to understand the structure-function relationships of different human immunoglobulins. In this context, we focus on four interconnected topics: 1) Biologics. We aim to arrive at personalized medicine with therapeutic antibodies, dissect the development of humoral tolerance to biologics, and characterization of anti-idiotype responses. 2) Biology of IgG4. We are interested in the question how IgG4-specific properties contribute to humoral tolerance or the lack thereof, and how do IgG4/Th2 responses develop and how they can be avoided (e.g. in case of anti-biological responses)? 3) Antibodies to antibodies in RA. We investigate the role of rheumatoid factors and anti-hinge antibodies in RA. 4) The role of Fab glycosylation in the humoral immune response, and the potential contribution of Fab glycans to the immunomodulatory properties of IVIg.

Technology

  • Clonal Ag-specific B cell characterisation & sequencing
  • (Recombinant) antibody engineering
  • Biophysical & immunochemical characterization of antibodies, immune complexes, and protein interactions
  • Development of novel immunoassays
  • Complement assays
  • HPLC
  • ELISA
  • RIA
  • ITC
  • Biacore/SPR
  • Fluorescence Spectroscopy
  • FRET
  • FACS

Resume

2011-present Staff member  Department  Immunopathology, Sanquin Research, Amsterdam
2006-2010 Post-doc Department Immunopathology, Sanquin Research
1999-2004 PhD student at the department of Organic Chemistry, University of Groningen
1994-1999 Physical and Organic Chemistry at the University of Groningen

Other publications

Rispens T, Engberts JBFN. Kinetic solvent effects on 1,3-dipolar cycloadditions of benzonitrile oxide. J Phys Org Chem 2005; 18:908.

Rispens T, Engberts JBFN. Cycloadditions in mixed aqueous solvents: the role of the water concentration. J Phys Org Chem 2005; 18:725.

Rispens T, Cabaleiro-Lago C, Engberts JBFN. Kinetics of hydrolysis of 4-methoxyphenyl-2,2-dichloroethanoate in binary water-cosolvent mixtures; the role of solvent activity and solute-solute interactions. Org Biomol Chem 2005; 3:597.

Rispens T, Lensink MF, Berendsen HJC, Engberts JBFN. Molecular dynamics simulation of the effect of hydrophobic cosolutes on the neutral hydrolysis of an activated ester. J Phys Chem B 2004; 108:5483.

Rispens T, Engberts JBFN. A kinetic study of 1,3-dipolar cycloadditions in micellar media. J Org Chem 2003; 68:8520.

Rispens T, Engberts JBFN. Micellar catalysis of Diels-Alder reactions: Substrate positioning in the micelle. J Org Chem 2002; 67:7369.

Rispens T, Engberts JBFN. Efficient catalysis of a Diels-Alder reaction by metallo-vesicles in aqueous solution. Org Lett 2001; 3:941.