Research
Ingemar Björkhem has studied the role of oxysterols during the last 5 decades. During the last decades emphasis was put on the role of oxysterols in the brain. In contrast to cholesterol itself these metabolites are able to pass the blood-brain barrier and Björkhem has shown that there is a continuous flux of the oxysterol 27-hydroxycholesterol from external sources into the brain and a flux of the oxysterol 24S-hydroxycholesterol from the brain into the periphery. The flux of 24S-hydroxycholesterol from the brain is dependent upon a cytochrome P-450 containing enzyme, cholesterol 24S-hydroxylase (CYP46), which is of critical importance for the cholesterol turnover in the brain. Björkhem and others have shown that both the flux of 27-hydroxycholesterol into the brain and the flux of 24S-hydroxycholesterol from the brain is of importance for the memory function and that the level of the two oxysterols in circulation and cerebrospinal fluid can be used as markers for the function of the brain. This has been shown both in clinical studies and in studies with different mouse models with increased or decreased formation of oxysterols. Björkhem has also characterized the enzymes involved in production and metabolism of 24S-hydroxycholesterol and 24S-hydroxycholesterol. The oxysterol balance in connection with Alzheimer´s disease, Huntington´s disease, has been characterized. Of particular importance is studies on patients with a genetic defect in 27-hydroxylation (Cerebrotendinous xanthomatosis). Björkhem has a close collaboration with clinical neuorologists in particular with prof. Angel Cedazo-Minguez and doc Silvia Maioli.
Ulf Diczfalusy has studied lipid metabolism, analytical biochemistry, oxidative stress and endogenous and exogenous markers of Cytochrome P450 3A (CYP 3A) enzyme activity. One oxysterol, 4b-hydroxycholesterol, was shown to be a good marker of CYP 3A4 and 3A5 enzyme activity and has been used by most major drug companies in their drug-drug interaction studies of new compounds. Diczfalusy has also studied other endogenous markers of CYP 3A activity like 1b-hydroxy-deoxycholic acid/deoxycholic acid.
Teaching assignments
Study programme in medicine.