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
Anna Karlsson
Professor/specialist physicianGroup members
Research techniques
- Cell and molecular biology
- Enzyme assays
- Transgenic models
External funding
The Swedish Research Council and the Swedish Cancer Society.
Teaching assignments
- The group is responsible for a microbiology course and lectures in virology at the various training programs.
- Examiner for project work in the BMA programme.
- Responsible for the area Scientific competence in the Curriculum Committee for the 6-year medical program.
Selected publications
Zhao, Q; Zhou, X; Kuiper, R; Curbo, S; and Karlsson, A. Compensatory nucleotide synthesis contributes to sufficient mtDNA levels for long term survival in Tk2 deficient liver tissue (Manuscript)
Zhou, X; Kuiper, R; Curbo, S; Karlsson, A. The 3-oxoacid CoA-transferase (OXCT1) axis initiates liver fibrosis in a primary mouse model with mitochondrial deficiency. (Manuscript)
Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2.
Zhao Q, Zhou X, Kuiper R, Curbo S, Karlsson A
PLoS One 2022 ;17(6):e0270418
Zhao, Q; Zhou, X; Kuiper, R; Curbo, S; and Karlsson, A. Specific depletion of thymidine kinase 2 in liver tissue does not affect mice survival. (Manuscript)
Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.
Zhou X, Mikaeloff F, Curbo S, Zhao Q, Kuiper R, Végvári Á, Neogi U, Karlsson A
Hum Mol Genet 2021 10;30(21):2012-2026
Severe mtDNA depletion and dependency on catabolic lipid metabolism in DGUOK knockout mice.
Zhou X, Curbo S, Zhao Q, Krishnan S, Kuiper R, Karlsson A
Hum Mol Genet 2019 09;28(17):2874-2884
Age-related metabolic changes limit efficacy of deoxynucleoside-based therapy in thymidine kinase 2-deficient mice.
Blázquez-Bermejo C, Molina-Granada D, Vila-Julià F, Jiménez-Heis D, Zhou X, Torres-Torronteras J, Karlsson A, Martí R, Cámara Y
EBioMedicine 2019 Aug;46():342-355
Metformin downregulates the mitochondrial carrier SLC25A10 in a glucose dependent manner.
Zhao Q, Zhou X, Curbo S, Karlsson A
Biochem Pharmacol 2018 10;156():444-450
Inhibition of glutamate oxaloacetate transaminase 1 in cancer cell lines results in altered metabolism with increased dependency of glucose.
Zhou X, Curbo S, Li F, Krishnan S, Karlsson A
BMC Cancer 2018 May;18(1):559
The Cellular Thioredoxin-1/Thioredoxin Reductase-1 Driven Oxidoreduction Represents a Chemotherapeutic Target for HIV-1 Entry Inhibition.
Reiser K, Mathys L, Curbo S, Pannecouque C, Noppen S, Liekens S, Engman L, Lundberg M, Balzarini J, Karlsson A
PLoS One 2016 ;11(1):e0147773
The mitochondrial carrier SLC25A10 regulates cancer cell growth.
Zhou X, Paredes JA, Krishnan S, Curbo S, Karlsson A
Oncotarget 2015 Apr;6(11):9271-83
Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells.
Bartesaghi S, Graziano V, Galavotti S, Henriquez NV, Betts J, Saxena J, Minieri V, A D, Karlsson A, Martins LM, Capasso M, Nicotera P, Brandner S, De Laurenzi V, Salomoni P
Proc Natl Acad Sci U S A 2015 Jan;112(4):1059-64
Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.
Krishnan S, Paredes JA, Zhou X, Kuiper RV, Hultenby K, Curbo S, Karlsson A
J Biol Chem 2014 Nov;289(47):32835-44
The many isoforms of human adenylate kinases.
Panayiotou C, Solaroli N, Karlsson A
Int J Biochem Cell Biol 2014 Apr;49():75-83
Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions.
Alston CL, Schaefer AM, Raman P, Solaroli N, Krishnan KJ, Blakely EL, He L, Craig K, Roberts M, Vyas A, Nixon J, Horvath R, Turnbull DM, Karlsson A, Gorman GS, Taylor RW
Neurology 2013 Dec;81(23):2051-3