Research interest: Deciphering molecular mechanisms that govern the T cell response
Our work is in the first place inspired by the desire to improve
immunotherapy of cancer. Sustaining survival and memory function of
T cells is expected to improve anti-tumor immunity. At the same
time, mechanisms we elucidate may be exploited to improve
vaccination against infectious disease and to block undesired
immune responses, as in auto-immunity and transplant rejection.
This work is carried out in vivo in mouse models and in matching
cellular systemsin vitro, whereby we presently focus on
interactions between T cells and dendritic cells. We collaborate
with biotech industry to validate therapeutic antibodies. A second
aim is to explore the concept of "immunogenic cell death" in the
context of radio- or chemo-immunotherapy. In this work, we combine
our expertise on T cell- and dendritic cell function with our
expertise on apoptosis signaling. This work is done for a large
part in cell modelsin vitro, using biochemical and cell biological
approaches. The link between basic cell biology and clinical
practice is made by studies in mouse tumor models. In this
translational work, we collaborate with the Division of
● Discovery of the CD3 gamma, delta and epsilon subunits of the
human T cell receptor/CD3 complex.
● Discovery of a novel human T-cell lineage expressing T-cell
receptor gamma/delta. Collaboration with other groups allowed us to
identify T cell receptor gamma/delta by biochemical means.
Independent work led to the generation and diagnostic use of the
first antibody that could identify cells expressing T cell receptor
gamma/delta in human blood and tissues.
● Discovery of the signal transduction complex associated with
human membrane immunoglobulin, alias the B cell antigen receptor
(BCR, a term coined by our group).
● Implication of various signaling molecules in the BCR pathway,
including Btk, c-Cbl and its mechanism of action.
● Identification of TNF receptor family member CD27 and its
ligand CD70 as an important T cell costimulatory system, critical
for the generation of effector and memory T cells.
● Elucidation of the mechanism underlying ceramide production in
response to apoptotic stimuli.
● Discovery of a novel mechanism of ubiquitination that
regulates apoptosis signaling by death receptors.