A novel target approach to characterize the Biosynthesis of Cholesterol in Cancer Cells

• Applicants: Dr. Sven Meckelmann; Professor Dr. Oliver Schmitz
• Subject Area: Analytical Chemistry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 463367585

Cholesterol is a very abundant lipid and extensively studied in the last decades, however, we have just begun to understand the role of cholesterol in cancer. Currently, it is getting more and more clear that cholesterol homeostasis plays an important role in tumor initiation and progression offering several new therapeutic targets for cancer treatment. However, how and why the cholesterol homeostasis and, therefore, the biosynthetic pathways are altered remains unknown to a certain extent due to many difficulties in the analysis of cholesterol and the corresponding precursors.Currently, GC-MS or LC-MS methods are used to characterize the cholesterol biosynthesis, and both suffer from i) problems with interfering matrix, ii) vastly different concentrations, iii) poor chromatographic separation of certain precursor, and iv) low inter-lab compatibility.To tackle these problems, we are proposing to develop a multidimensional liquid chromatographic heart-cut method (LC-LC) that allows separating cholesterol and its biosynthetic precursors in one chromatographic analysis. Moreover, to ionize these compounds with high efficacy we will build an inverse low-temperature plasma (iLTP) ion source that is less prone to matrix interferences compared to other ionization techniques such as ESI and well suited for the ionization of middle- to non-polar compounds. In the final stage, we will apply this method to study-metastasis in pancreatic cancer (cooperation with AK Grüner) and -the tumor progression in melanoma (cooperation with AK Paschen).The results will be essential for both groups in their further attempt to understand the underlying biology in both types of cancer.

• DFG Programme: Research Grants