Research group - Anna Karlsson
Nucleosides, nucleotides and nucleoside analogues; their metabolism and function and their potentials as therapeutic targets.
Our research group studies how DNA building blocks are formed and how to modify this synthesis so that the DNA chain cannot be copied. The group of drugs that act as inhibitors by making false DNA building blocks is called nucleoside analogues and is used to treat both viral diseases and cancer. A prerequisite for the nucleoside analogues to be active, they must become phosphorylated to the corresponding triphosphates by either viral or cellular enzymes and then inhibit viral or cellular DNA synthesis. We study the enzyme systems needed to activate these drugs inside the cells. The activation can be described as a three-stage rocket in that different phosphate groups are added in three subsequent steps. Thereafter, the drug can stop the synthesis of the DNA chain. An important area of our research is to explore new targets for the treatment of HIV and to understand what causes the side effects of treatment. Side effects are often caused by disturbed mitochondrial function by the nucleoside analogues inhibiting the mitochondrial DNA synthesis.
In our studies of how the building blocks of mitochondrial DNA are formed, we have also another important applications of our research. It is to understand the mechanism of some diseases caused by improper functioning of the cell's mitochondrial DNA synthesis.
Research group leader Anna Karlsson
- Cell and molecular biology
- Enzyme assays
- Transgenic models
The Swedish Research Council and the Swedish Cancer Society.
The group is responsible for a microbiology course and lectures in virology at the various training programs.
Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency.
Krishnan S, Zhou X, Paredes JA, Kuiper RV, Curbo S, Karlsson A
J. Biol. Chem. 2013 Feb;288(7):5072-9
Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.
Zhou X, Kannisto K, Curbo S, von Döbeln U, Hultenby K, Isetun S, et al
PLoS ONE 2013 ;8(3):e58843
Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.
Paredes JA, Zhou X, Höglund S, Karlsson A
PLoS ONE 2013 ;8(1):e53698
Thioredoxin-1 and protein disulfide isomerase catalyze the reduction of similar disulfides in HIV gp120.
Reiser K, François KO, Schols D, Bergman T, Jörnvall H, Balzarini J, et al
Int. J. Biochem. Cell Biol. 2012 Mar;44(3):556-62