Head Department of Cell and Chemical Biology, LUMC, Leiden, the Netherlands
Neefjes is studying the molecular and cell biology of antigen processing and presentation by MHC class I and MHC class II molecules. Neefjes’ team has solved many steps in our current understanding of the MHC class I and MHC class II cell biology. This work is broadly applied in modern immunotherapy approaches. He is now combining that with genetic and chemical screens to find new targets and new leads for manipulation.
Neefjes has developed a number of unique lines of research with implications for cancer. These include the molecular basis for radio-immunotherapy and drug development for chemo-immunotherapy in cancer. Other lines of research include the relationship between bacterial infections and cancer. Neefjes showed the link between Salmonella Typhi infections and gallbladder carcinoma and most recently the link between another Salmonella serovar, Salmonella Enteritidis and colon cancer risk.
His research at the interphase of these disciplines resulted in a cell biological study on the activities of doxorubicin, a heavily used anti-cancer drug. Although reported in over 100,000 publications as a topoII poison that generates DNA breaks, Neefjes identified a second activity; histone eviction at defined sites in the genome. This work was extended to identify variant drugs that are active in oncology but lack the different side effects, including cardiotoxicity. The re-analysis of old drugs with new technologies offers the opportunity of modifying compounds to alter their activities and remove (some of) the therapy-limiting side effects, as will be presented.