Expertise:

Cell culture techniques, Molecular biology techniques

Biochemical assays, Proteomics

PhD Project: Lipid hydrolysis in lung cancer metabolism

Lung cancer is the leading cancer-related cause of death worldwide ¹. On a molecular level, cancer cells undergo sophisticated metabolic changes in order to survive and thrive in challenging environments. A widely observed cancer hallmark is the switch from oxidative energy production to a fermentation process, even under availability of oxygen; a phenomenon that is termed the Warburg-effect ². More recently, aberrant lipid metabolism has emerged as another hallmark of cancer with features such as increased fatty acid (FA) synthesis and uptake as well as accumulation of intracellular lipid droplets (LDs) ^3,4. Through my project, we aim at broadening our understanding about the relationship between aberrant lipid mobilization from LDs and metabolism in lung cancer cells. Specifically, we are interested in the rate-limiting enzyme of intracellular lipid hydrolysis - adipose triglyceride lipase (ATGL) - and its role in lung cancer progression.

We use human lung cancer cell lines as a model to investigate metabolic changes and tumor progression in lung cancer based on changes in intracellular lipolysis. We therefore established genetically modified human lung cancer cell lines with increased or decreased levels of ATGL. In addition to 2D cell culture, we employ 3D cell culture techniques as a better representation of the in-vivo situation of solid tumors (e.g. nutrient and oxygen availability gradient).

In addition to standard biochemical assays and microscopy workflows, we perform high resolution mass spectrometry based proteomic analysis to link changes in the proteome to the observed changes in phenotype and metabolic status of the cells (e.g. differences in growth, migration, glucose consumption and lactate production).

¹ Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 68, 394–424 (2018).
² Ward, P.S. & Thompson, C.B. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21, 297-308 (2012).
³ Currie, E., Schulze, A., Zechner, R., Walther, T.C. & Farese, R.V., Jr. Cellular fatty acid metabolism and cancer. Cell Metab 18, 153-161 (2013).

⁴  Cruz, A.L.S., Barreto, E.A., Fazolini, N.P.B., Viola, J.P.B. & Bozza, P.T. Lipid droplets: platforms with multiple functions in cancer hallmarks. Cell Death Dis 11, 105 (2020).