Our focus within the area of pharmacogenetics is the importance of genetic variation in the context of treatment of childhood leukemia (ALL) and inflammatory bowel disease (IBD).
One of the important polymorphic enzymes we are studying is thiopurine methyltransferase (TPMT). Approximately 10 % of the population carries genetic variants in this genes, causing a defect enzyme. TPMT has an important role in detoxifying thiopurines, drugs used for treatment of ALL and IBD. Loss of TPMT enzyme activity leads to higher concentrations of toxic metabolites, and thereby increased risk for adverse drug reactions, that could be lethal.
We aim to address the research questions both in clinical studies and mechanistically in cell lines and using recombinant proteins.
By studying recombinant TPMT with biophysical techniques such as Circular Dichroism (CD), Isothermal Titration Calorimetry (ITC) and Flourescence, we are for example able to study the difference in protein stability and drug affinity between TPMT and the various genetic variants. This work is a collaboration with Lars-Göran Mårtensson.
TPMT nomenclature committee - Naming of genetic variants in the TPMT gene
Together with international partners, I run the TPMT nomenclature committee, which works with the mapping and naming of genetic variants in the TPMT gene. Please see our website TPMT nomenclature committee, for more information. A paper was published in 2013 describing the work of the TPMT nomenclature committee (Appell ML et al., 2013 Pharmacogenetics and Genomics 2013, 23:242-248).