2. Antisecretory and antiproliferative function of a 78 kD mast cell phosphoprotein. We sequenced this protein which, in its phosphorylated state, inhibits mast cell secretion irrespective of the stimulus. We are investigating the regulation of its expression, identification of the phosphorylated sites and molecules which increase and sustain the phosphorylated state of this protein. Such compounds would be the first truly anti-allergic drugs.

3. Regulation of secretion by ornithine decarboxylase and polyamines. Naturally occurring polyamines and their oxidative metabolites inhibit mast cell secretion even though secretion is triggered by polycationic compounds. We are studying the mechanism of this inhibition and the possibility of using such polyamines clinically.

4. Pathophysiology of mast cells in neuroimmunoendocrine disorders. Mast cells are known for their involvement in allergic reactions, but we have shown them to participate in the pathophysiology of neuroimmunoendocrine syndromes with high prevalence in women such as interstitial cystitis, irritable bowel syndrome, migraine headaches and multiple sclerosis. We have developed in vivo and in vitro models for these diseases and we are studying neurohormonal activation of mast cells and drugs, which inhibit this effect. In particular, we have measured mast cell mediators in urine of interstitial cystitis patients, which may be used to easier diagnose this syndrome. A clinical study is now in progress at the NEMC Clinical Research Center to investigate the ability of a mast cell secretion inhibitor to reduce interstitial cystitis symptoms.