Adaptive remodelling of metabolism during liver regeneration

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  Project Leader
  Dr Andrew Cox

  andrew.cox@petermac.org

  View researcher's webpage

  +61 3 8559 5439

Project Details

Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. The process of liver regeneration is multifaceted, as it requires a complex tissue comprised of multiple cell types to sense the extent of injury and mount an appropriate compensatory regrowth response. However, despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. Consequently, there is a need to better understand the molecular and cellular mechanisms that initiate liver regeneration. Nrf2 is a transcription factor that plays a pivotal role in the cell’s adaptation to stress. We previously identified that stimulation of the Nrf2 pathway upon liver injury facilitates regeneration. Recently, we have pioneered the use of integrated metabolomic and transcriptomic approaches in zebrafish to identify how metabolic remodelling impacts organ growth. We now have preliminary evidence that Nrf2 plays a key role in metabolic remodelling upon liver injury and is required for liver regeneration. Therefore, we are uniquely positioned to examine the mechanism by which Nrf2 remodels metabolism to fuel liver regeneration. This project will deliver new insights into the fundamental biological question of how metabolic remodelling is coordinated with tissue growth and regeneration.

Building on these studies, we currently have research projects that aim to…

• To determine the role that Nrf2 plays in adaptive metabolic remodelling during regeneration.
• To characterize a new injury model in zebrafish that recapitulates chronic liver disease.
• To elucidate the dynamics of liver regeneration at the cellular level by in vivo imaging.

Research Opportunities

This research project is available to Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

1. Cox AG*, Tsomides A, Yimlamai D, Hwang KL, Miesfeld J, Galli GG, Fowl BH, Fort M, Ma KY, Sullivan MR, Hosios AM, Snay E, Yuan M, Brown KK, Lien EC, Chhangawala S, Steinhauser ML, Asara JM, Houvras Y, Link B, Vander Heiden MG, Camargo FD, Goessling W (2018). Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. EMBO J. 37(22). pii: e100294. * Co-corresponding author.
2. Cox AG, Tsomides A, Kim AJ, Saunders D, Hwang KL, Evason KJ, Heidel J, Brown KK, Yuan M, Lien EC, Lee BC, Nissim S, Dickinson B, Chhangawala S, Chang CJ, Asara JM, Houvras Y, Gladyshev VN, Goessling W (2016). Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis. Proc Natl Acad Sci USA. 113(38):E5562-71.
3. Cox AG, Hwang KL, Brown KK, Evason KJ, Beltz S, Tsomides A, O'Connor K, Galli GG, Yimlamai D, Chhangawala S, Yuan M, Lien EC, Wucherpfennig J, Nissim S, Minami A, Cohen DE, Camargo FD, Asara JM, Houvras Y, Stainier DY, Goessling W (2016). Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol. 18(8):886-96.