Specialization
Focus of research
We conduct basic and translational research aimed at understanding the role of the humoral immune response in disease and to optimize biopharmaceutical therapies. In order to achieve this, we develop biophysical and immunochemical methodology to investigate structure-function relationships of immunoglobulins in a basic and clinical setting. Besides conducting basic research, we aim to translate our findings into the clinic and convert methodology into diagnostic tools.
Structure & function of antibodies
A key feature of antibodies is their enormous structural variation. Combined with the vast range of immune receptors/effector molecules that may interact with antibodies and the virtually unlimited range of antigens they can bind to, one can appreciate that it is only partially understood how the many functions of immunoglobulins relate to their structural variability. We conduct structure-function research of antibodies in a clinical setting, aimed at dissecting pathological or immunomodulatory properties of antibodies. Topics include:
- Role of Fab glycosylation in the humoral immune response
- Structural and functional stratification of autoantibody responses
- Biological impact of antibody polymorphisms
Therapeutic drug monitoring of biologics
The use of biologics has drastically altered the prognosis and treatment options in many inflammatory and autoimmune diseases. Therapeutic antibodies are often highly effective but do not always work. The current paradigm for most biologics is a 'one-size-fits-all' approach, i.e., fixed dosing schemes regardless of disease state, patient genetics, etc. However, this can result in a huge variation in concentrations of circulating drugs, for instance, in case of TNF inhibitors, and retrospective studies demonstrate a clear relationship between drug concentration and clinical efficacy. With many new biologics recently approved or still in development, these therapies are also becoming a major financial burden, and research aimed to arrive at cost-effective use of these therapies is urgently warranted. From this perspective, we conduct studies on the following topics:
- Personalized medicine of therapeutic antibodies
- PK/PD monitoring & prediction
- Causes and consequences of immunogenicity
IgG4 biology & humoral tolerance
IgG4 antibody responses are unique to humans. IgG4 antibodies have impaired pro-inflammatory activity, and may counteract pathogenic IgE in case of allergy. However, IgG4 antibodies can also constitute a major part of various pathogenic autoantibodies and neutralizing antibody responses to therapeutic proteins or biologics. These unwanted responses have a distinct but poorly understood immunological signature, including elevated levels of Fab glycosylation, a slow but progressive increase of the IgG4 fraction, and a sometimes transient nature. We aim to understand the causes and consequences of this class of human antibody responses, and our research includes the following topics:
- Role of IgG4 in humoral tolerance
- Dynamics of IgG4/Th2 responses
- Dissecting the development of humoral tolerance to biologics
Technology
- Biophysical & immunochemical characterization of antibodies, immune complexes, and protein interactions
- Clonal Ag-specific B cell characterization & sequencing
- (Recombinant) antibody engineering
- Development of novel immunoassays
- Complement assays