DR. ROZBEH JAFARI, DR. MATTIAS VESTERLUND and DR. JÜRGEN EIRICH
Our overall aim in the Childhood Cancer team is to use mass spectrometry based proteomics to increase our biological understanding of Acute Lymphoblastic Leukemia (ALL) and Neuroblastoma, define clinical subtypes, evaluate drug interactions and identify biomarkers for targeted thereapies, improving personalized therapy.
Childhood ALL is the most common pediatric cancer accounting for roughly 75-80% of all childhood cancer cases. Although many of the patients achieve complete remission and are cured by standard therapies, patients’ relapsing in the disease have a poor prognosis. Treatment of relapsed ALL is overall more intense and is affecting the quality of life considerably. Therfore the resistance development and long-term side effects of current broad cytotoxic therapy of ALL has warranted novel predictive biomarkers as well as novel targeted drug therapeutics.
We are engaged in using Thermal Proteome Profiling and in-depth proteogenomics for identifying novel predictive resistant and therapeutic biomarkers for a more effective personalized therapy in treatment of pediatric ALL.
Acute Lymphoblastic Leukemia
MARTINEZ MOLINA D*, JAFARI R*, IGNATUSHCHENKO M*, SEKI T, LARSSON EA, DAN C, SREEKUMAR L, CAO Y, NORDLUND P. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science (New York, N.Y.) 2013 341;6141 84-7 doi:10.1126/science.1233606 *These authors contributed equally to this study.
SAVITSKI MM, REINHARD FB, FRANKEN H, WERNER T, SAVITSKI MF, EBERHARD D, MARTINEZ MOLINA D, JAFARI R, DOVEGA RB, KLAEGER S, KUSTER B, NORDLUND P, BANTSCHEFF M, DREWES G. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science (New York, N.Y.) 2014 346;6205 1255784 doi:10.1126/science.1255784
JAFARI R, ALMQVIST H, AXELSSON H, IGNATUSHCHENKO M, LUNDBACK T, NORDLUND P, MARTINEZ MOLINA D. The cellular thermal shift assay for evaluating drug target interactions in cells. Nature protocols 2014 9;9 2100-22 doi:10.1038/nprot.2014.138
ALMQVIST H*, AXELSSON H*, JAFARI R, DAN C, MATEUS A, HARALDSSON M, LARSSON A, MARTINEZ MOLINA D, ARTURSSON P, LUNDBACK T, NORDLUND P. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil. Nature communications 2016 7; 11040 doi:10.1038/ncomms11040 *These authors contributed equally to this study.