The processes that a cell needs for self-maintenance and conducting its functions are regulated by biochemical reactions. During the course of these reactions, metabolites are formed, converted or degraded, which provides information about the cell’s condition and functional capacity. Both environmental and genomic factors influence the cellular state and actions. As such, the metabolites in a cell allow us to measure the interactions between several factors that influence cell health and growth. The presence and quantity of metabolites have the potential to function as biomarkers differentiating between disease states and potentially providing information on therapy success or failure. Hence, several MSTARS partners focus on a MS-based analysis of metabolites and have joined forces to implement standardized and advanced metabolomic analyses in the clinics and to identify metabolomic signatures that support therapy recommendations.
Kirwan Lab
Jennifer Kirwan and her group have long-standing expertise in the field of MS metabolomics addressing the interaction of metabolites in cells and body fluids to investigate diseases, their causes and potential treatments in a new and in-depth manner. AG Kirwan uses a plethora of mass spectrometric methods, such as gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), direct infusion MS (DIMS), liquid extraction surface analysis MS, or ultrahigh field asymmetric ion mobility spectrometry, to shed light on the aetiology of diseases and to discover new treatment options.
In the context of the MSTARS consortium, AG Kirwan uses quantitative and targeted as well as semi-quantitative and untargeted analyses via DIMS, GC-MS and LC-MS, to create a broad profile of metabolic changes in different disease entities and to address metabolic adaptations following drug treatment for the primary use-case HNSCC. To pave the way for the implementation of metabolic analyses in the clinics, protocols for sample processing are being established that allow standardized and robust workflows. The focus of the analyses are tryptophan metabolites that are known to be important for the regulation of mTOR, the functioning of the immune systemand the interaction of hosts with their microbiome.
Kempa Lab
The interaction of genes, proteins and metabolites is central for cellular processes and alterations provide information about healthy and diseased conditions. The lab of Stefan Kempa seeks to decipher the crosstalk between metabolism and gene regulation, with a special focus on the metabolic regulation and its impact on cellular differentiation and cancer formation. In order to study the dynamics of metabolism the Kempa lab established a variety of MS-based proteomics and metabolomics methods that allow analyses under in vitro and in vivo conditions. Specifically, they developed and patented a workflow called pulse stable isotope-resolved metabolomics (pSIRM) that provides a dynamic, time-resolved quantitative measurement of the central metabolism.
As part of the MSTARS consortium, the group of Stefan Kempa uses pSIRM to analyze the effect of drug treatments on the central carbon metabolism. Several drugs for cancer treatment affect the cellular DNA synthesis to restrict the proliferation of tumor cells. Along that line, the team analyzes intermediates of the nucleotide biosynthesis to address the question whether the drug treatment is reflected in the metabolome with a focus on the nucleotide metabolism. In addition, they seek to understand how the phenotype can be translated to clinical parameters and will integrate the metabolome with proteome and imaging data to receive a multimodal profile of treatment responses. Advancing the method of nucleotide profiling for routine applications in preclinical models and tumor biopsies is the overarching goal for Stefan Kempa’s team.