My laboratory studies autoimmune diseases and cancers of the lymphoid system. We aim to delineate molecular differences between pathologic and normal tissues that can serve as targets for therapy. We have discovered two new targets during the last year.
Chronic lymphocytic leukemia cells and some lymphoma cells are hypersensitive to chemical inhibitors of microtubule polymerization, even though the malignant cells divide very slowly. The molecular basis for the hypersensivity is not known, and thus has been difficult to exploit therapeutically. We discovered that the apparently quiescent malignant lymphocytes turn over their microtubules at an abnormally rapid pace, to facilitate cell movement through the body. We synthesized a low molecular weight inhibitor of tubulin turnover, called indanocine, that kills the leukemia and lymphoma cells, without harming normal lymphocytes.
In rheumatoid arthritis, the normally thin joint lining turns into lymphoid granulation tissue that produces autoantibodies and cytokines. Why the abnormal tissue persists in an anomalous site is not known. We discovered that the normal appearing joint lining cells of rheumatoid arthritis patients, but not control subjects, express high levels of receptors of the wnt and frizzled family that regulate limb bud formation during embryogenesis. Moreover, interference with signaling through the wnt5a pathway blocked the formation of inflammatory cytokines