Antimetabolites, Antineoplastic; Basal Metabolism; Biochemical Processes; Carbohydrate Metabolism; Cell Culture Techniques; Cloning, Molecular; Computational Biology; DNA, Recombinant; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Genetic Engineering; Lipid Metabolism; Microbiological Techniques; Models, Structural; Nutrigenomics; Oncolytic Virotherapy; Point Mutation; Recombinant Proteins; RNA Interference; Xenograft Model Antitumor Assays
Since we discovered that L-carnitine acts as a nutrigenomical factor that heavily influnces the whole genome, we developed cell culture model systems to study carnitine deficiency in human liver, muscle and fibroblast cells. This allowed us to investigate the the “L-carnitine effect”, in the connex to clinical pathologies of hyperlipidemia, hyperglycemia, insulin resistance and type 2 diabetes mellitus. We want to reveal so called “candidate or susceptibility” genes, which are associated with these diseases. The results will provide better insight in metabolic aspects of pathologies and their regulation as well as mitochondrial function. In a second research area we focussed on the use of cytotoxic or cytostatic genes suitable for gene therapy of solid cancers. First it was necessary to establish different expression systems that enabled us to identify and optimize the use of such genes. On one hand we used a plasmid driven tetracyclin inducible eukaryotic expression vector to generate stable transformants of cytotoxic genes in human primary cancer cells. In paralell we took advantage of an AAV recombinant vector system to infect any cancer cell and artifically express the toxic trojan horse gene. Bothe systems are optimal in identifying, establishing and optimizing this cance gene therapy approach.
Techniques, methods & infrastructure
Cell culture model systems for hyperlipidemia, hyperglycemia and L-carnitine deficiency, genomic approaches, microarrays, real-time RT-PCR for the analysisi of steady state mRNA levels, molecular and biochenical techniques to analyse protein and enzyme fluctuations, cell biological techniques and FACS analysis, in vitro mutation and genetic engineering, structural aspects of proteins and their computation, molecular oncology and gene therapy with the identification and optimization of the use of cytotoxic/cytostatic genes, bacterial and virological microbiology, establishment of xenotransplants of human cancers in mouse model organisms
- The investigation of the L-Carnitine sensing transcription factor complex under normal and hyperglycemic and hyperlipidemic conditions (2015)
Source of Funding: Herzfelder'sche Familienstiftung,
- Kienesberger, K. et al., 2014. L-carnitine and PPARα-agonist fenofibrate are involved in the regulation of Carnitine Acetyltransferase (CrAT) mRNA levels in murine liver cells. BMC Genomics, 15(1), p.514. Available at: http://dx.doi.org/10.1186/1471-2164-15-514.
- Blake, S.M. et al., 2008. Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration. The EMBO Journal, 27(22), pp.3069-3080. Available at: http://dx.doi.org/10.1038/emboj.2008.223.
- Godarova, A. et al., 2005. L-Carnitine Regulates mRNA Expression Levels of the Carnitine Acyltransferases - CPT1A, CPT2, and CRAT. Monatshefte für Chemie - Chemical Monthly, 136(8), pp.1349-1363. Available at: http://dx.doi.org/10.1007/s00706-005-0336-5.
- Hofbauer, R. et al., 2005. Chronic Hemodialysis and Pregnancy - L-Carnitine Supplementation to Human Sera in Vitro is Restoring Normal Expression Levels of Carnitine Acyltransferases. Monatshefte für Chemie - Chemical Monthly, 136(8), pp.1509-1521. Available at: http://dx.doi.org/10.1007/s00706-005-0338-3.
- Lohninger, A. et al., 2005. Endurance Exercise Training and L-Carnitine Supplementation Stimulates Gene Expression in the Blood and Muscle Cells in Young Athletes and Middle Aged Subjects. Monatshefte für Chemie - Chemical Monthly, 136(8), pp.1425-1442. Available at: http://dx.doi.org/10.1007/s00706-005-0335-6.