Neefjes combines chemistry with cell biology and immunology with the aim to develop tools to manipulate the immune system and cancer biology. The work is focused on three areas:
Understanding the biology of MHC class I and MHC class II molecules
By combining genetic screens with chemical library screens both biology and chemical tools connected to the biology can be identified. The cell biology with have broad and sometimes defined consequences for various biological processes.
The contribution of bacteria in the development of tumors
This work is based on our original finding that AKT kinase was activated by bacteria such as Salmonella and M.tuberculosis to prevent their destruction in lysosomes. This yielded the first antibiotics acting on the infected host rather than pathogen. We subsequently showed that the same pathway contributed to the increased risk of gallbladder carcinoma with chronically infected typhoid carriers in India. We are combining cell biology with bacterial infection studies and epidemiology to find more relations between bacterial infections and cancer. These tumors can then be easily prevented.
The cell biology of anti-cancer drugs
We have focussed on the anthracycline class of drugs that are one of the most used drugs in oncology. We have identified a novel mode of action of these drugs; histone eviction which results in epigenetic modifications. We have both initiated a chemistry line to synthesize away some of the side effects of this drugs and a line of cell biology and genetics/bioinformatics to better understand the drugs. The aim is to find within the chemical space of these drugs new variants with unique effects both in the lab and –preferably- in the clinic.