The most desired goal in bone marrow
and organ transplantation as well as in autoimmune medicine is the development
of drugs that will specifically and effectively target disease-related T
lymphocyte clones with very few side effects. The treatment with the currently
available chemical immunosuppressive drugs in the clinic is accompanied by severe
side effects and is sometimes not effective in suppressing the disease. This is
because, on the one hand, they attack biological processes that exist not only
in the target cells but also in many other tissues in the body, and on the
other they do not suppress all the T-cell-dependent immune mechanisms.
In-depth research in our lab on the
molecular processes in T cell activation has led to the identification of
unique primary events that trigger the chains of signaling pathways responsible
for this activation. Next, we established analytical systems that monitor and
quantify these signaling events and asked how they can be inhibited.
In collaboration with the Computational
Biology Unit at the Blavatnik Center for Drug Discovery at Tel Aviv University,
we looked for small molecules capable of inhibiting these events. The search
was done using a method of Molecular Dynamic Simulation, which produced a
series of small molecules that were tested in the experimental model we set.
Some of these molecules have been shown
to be capable of inhibiting different T cell signaling pathways and are
currently being investigated in depth to increase their inhibitory activity.
Next, the selected molecules will be
tested for their ability to inhibit T cell activation in vitro in
culture and then in vivo in autoimmune disease and transplantation
experimental models in animals.