Lo Persson, professor
The molecular mechanisms involved in the regulation of the amines we study may provide potential targets for therapeutic agents against a variety of diseases ranging from malaria to cancer.
Cellular proliferation, differentiation and death are all processes playing an active role from embryogenesis to the function of the adult organism. These events are strictly regulated and highly dependent on a multitude of intra- and extra-cellular factors to proceed normally. The polyamines constitute a group of intracellular growth factors essential for a large variety of cellular processes. Depletion of polyamines rapidly induces cell growth arrest, whereas too high levels may cause an induction of cell transformation or cell death. Thus, it is crucial for cells to maintain their polyamine concentrations within rather narrow limits.
Polyamine antimetabolites are potential drugs against a large variety of diseases. DFMO, which inhibits the enzyme catalyzing the rate-limiting step in polyamine biosynthesis, is presently the most effective drug against African sleeping sickness. It is capable of curing the most severe cases, in which also the central nervous system is affected. The drug has consequently been dubbed "the resurrection drug". Furthermore, several agents interfering with polyamine biosynthesis or function are presently being tested as chemopreventive and antineoplastic tools.
Our research deals with two major aspects of polyamine research. One is to elucidate the molecular mechanisms involved in the cellular control of polyamine homeostasis. The regulation occurs at many levels and involves unique mechanisms.
The second part of the project deals with the polyamine biosynthetic pathway as a potential target for anti-protozoan drugs. The enzymes involved and their regulation are characterized in a variety of protozoan parasites. In addition, we are studying the molecular regulation of the biosynthesis of another biogenic amine, namely histamine, which is involved in a variety of physiological and patophysiological processes, like gastric acid secretion, neurotransmission and inflammation.