Forschung Gottfried Schatz Forschungszentrum

Research focus: Metabolism

PI: Andreas Prokesch

Focus: Fasting regimens, like intermittent or periodic fasting, and caloric restriction have been shown to ameliorate a number of disease symptoms and to increase health span and even longevity in many model organisms from bacteria to non-human primates. While the first clinical trials are underway, the molecular mechanisms underlying these beneficial effects remain largely elusive. In our lab we investigate the impact of fasting on transcription factor networks in different cellular contexts. Our current projects focus on the transcription factor and tumour suppressor p53 as key player in the systemic fasting response using novel mouse models and genome-wide methods. In another project we scrutinize fasting in combination with molecular therapies in hepatocellular carcinoma.

Network: We cooperate on an ongoing basis with groups within the Research Centre (J. Feichtinger, D. Kratky, T. Madl, R. Malli), as well as within Med Uni (A. Deutsch, S. Frank, E. Heitzer, J. Kargl, I. Klymiuk, A. Reinisch, B. Rinner, S. Sedej) and the University of Graz (R. Schreiber). In the clinical field we collaborate with the working groups of M. Pichler (oncology), T. Pieber (endocrinology) and P. Schemmer (surgery). International cooperation partners are: Charité Berlin (M. Schupp), the German Institute of Human Nutrition (T. Schulz), Max Planck Institute Dresden (M. Huch), INSERM Nice (J. Jaeger), Helmholtz Zentrum München (S. Herzig), ETH Zurich (C. Wolfrum), University Utrecht (A. Heck) and the University of Pennsylvania (M. Lazar).


Interactome analysis of p53 signalling under nutrient stress

  • As an important tumour suppressor and transcription factor, p53 is an essential node linking stress stimuli to the regulation of target genes in normal and transformed cells. Intracellular p53 levels are regulated by a complex protein interaction network. In this project, we are investigating the precise molecular mechanisms of p53 stabilisation after nutrient deprivation, as well as the downstream signalling using proteomics methods to determine compartment-specific p53 interactomes (ChIP-MS, BioID) and transcriptomics to define starvation-specific p53 target genes.
  • Duration: 2017-2021
  • Funded by: FWF, Stadt Graz, Med Uni Graz, Lanyar Stiftung, EMBO, Horizon 2020 (EPIC-XS)
  • Project partners: Charité Berlin (Schupp), Deutsches Institut für Ernährungsforschung (Schulz), University Utrecht (Heck), Med Uni Graz (Madl, Frank, Heitzer)

p53 as coordinator of adipose fasting response

  • Obesity is associated with many metabolic diseases such as type 2 diabetes. The various fat depots play an essential role in systemic energy homeostasis. We investigate the influence of p53 on adipocyte development and function, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue in the context of fasting and high-fat diets. To this end, we investigate novel in vivo and in vitro model systems using a spectrum of molecular, biochemical, and omics methods, with the aim of identifying new therapeutic targets for the control of obesity-associated diseases.
  • Duration: 2017-2021
  • Funded by: FWF, PhD faculty MolMed
  • Project partners: Charité Berlin (Schupp), Deutsches Institut für Ernährungsforschung (Schulz), INSERM Nice (Jaeger), University Utrecht (Heck), ETH Zürich (Wolfrum), Helmholtz Zentrum München (Herzig), Med Uni Graz (Klymiuk, Kratky, Madl), Uni Graz (Zechner)

Fasting to target metabolic flexibility in heptatocellular carcinoma (HCC) therapy

  • Cancer cells are metabolically vulnerable due to their insatiable consumption of nutrients to support their growth. We are investigating whether fasting can improve the efficacy of current HCC treatments. To this end, we are working with cell lines, xenografts, chemically induced transgenic cancer models and patient-derived organoids, to study metabolic and transcriptional changes caused by the combination of fasting and molecular therapeutics. Recently, we were able to show that fasting massively increases the efficiency of standard therapy in a p53-dependent manner in HCC.
  • Duration: 2016-2023
  • Funded by: FWF, ÖNB, MEFO Graz, Horizon 2020 (EPIC-XS)
  • Project partners: Max Planck Institut Dresden (Huch), University Utrecht (Heck), Med Uni Graz (Deutsch, Heitzer, Kargl, Madl, Malli, Pieber, Reinisch, Rinner, Pichler, Schemmer)

Transcriptome and chromatin landscape (TCL) of fasting

  • In this project, we are working on how tissue-specific changes in TCLs coordinate the immediate cellular response to nutrient withdrawal and which specific aspects of the TCL manifest in a cellular fasting memory that mediates long-term effects. Using innovative NGS-based methods, such as GRO-seq and single cell ATAC-seq, we will derive a comprehensive atlas of acute and long-term TCL changes in tissues relevant to homeostasis under fasting. The results will help to understand how the beneficial effects of fasting are coordinated at the tissue, cell, and ultimately, at genome level.
  • Duration: 2021-2024
  • Funded by: FWF
  • Project partners: University of Philadelphia (Lazar), University Utrecht (Heck), Med Uni Graz (Feichtinger, Klymiuk, Madl)

Division of Cell Biology, Histology and Embryology

Assoz.-Prof. Priv.-Doz. Dr.
Andreas Prokesch  
T: +43 316 385 71901

Video explaining the findings of our 2022 Science Advances paper in a nutshell

How fasting can improve liver cancer therapy

Fasten bei Leberkrebs

Erforschung der molekularen und metabolischen Vorgänge.