Thiopurine drugs are cell toxic drugs used to treat acute lymphoblastic leukemia, inflammatory bowel diseases and rheumatism. We study how small variations in our genes affect how the body converts thiopurine drugs to active metabolites with medical effects. We are also studying drug interactions, how simultaneously treatment with more than one drug can affect the effect of the other.
Our focus is on the enzyme thiopurine methyltransferase (TPMT) which is known to be important for the body´s conversion into drug metabolites. About 10 % of the population is carrying a variant in the gene coding for TPMT which cause a less functional enzyme. To be able to study why the enzyme is not working as it should be, we are producing the human TPMT enzyme with E.Coli bacteria and are studying its stability and function with biophysical methods. We are also studying other potential markers for personalized treatment and develop methods for control of individualized treatment.
Methods in my projects
- Cell culturing
- HPLC and LC-MS/MS
- Protein, DNA and RNA extraction
- Real-time PCR
- DNA sequencing
- Site directed mutagens
- Expression of recombinant TPMT with E.Coli
- Fluorescence (tryptophan quenching, competitive binding)
- Circular dichroism, CD