Welcome on the Necker-Enfants Malades Institute website

from basic science:
to the translational research:
Ganna Panasyuk

Focus

Our research revolves around the fundamental questions of how nutrients are sensed and how this information drives basic functions of life.

 

Nutrient sensing enables metabolic homeostasis by matching energy use with fuel availability. The vast body of knowledge on pro-growth nutrient sensors, such as insulin and phosphoinositol-3 kinase (PI3K) signalling exposed the missing links in molecular coordination of degrative metabolic activities known as catabolism. The cellular catabolism relies on mitochondrial activities and on lysosomal pathway of autophagy, both paced by the circadian clock. We aim to understand how PI3K nutrient sensors synchronize metabolic activities in healthy tissue and what are the consequences of their dysfunction in human disease.

 

We are honoured to have a generous support of our research program from European (ERC-CoG MetaboSENS) and French national agencies (ANR, FRM) as well as INSERM, CNRS, industrial partners (ADDMedica) and patient associations (VML).

 

Panasyuk Lab 2019

 

For more information about our research, open positions and our news please visit http://panasyuklab.fr

Research objectives

We focus on class 3 PI3K, the only PI3K present in all eukaryotes from yeast to plants and animals. We have discovered its essential function for catabolic homeostasis in vivo (Nemazanyy, EMBO MM, 2013; Nemazanyy, Nature Comm, 2015; Iershov Nature Comm, 2019). In the on-going projects, we seek to:

- Identify the regulatory complexes of class 3 PI3K that serve its catabolic integrator function
- Reveal the physiological regulation of class 3 PI3K and its reciprocal impact on metabolic timekeeping
- Discover genetic alterations in class 3 PI3K signalling in inborn metabolic diseases
- Translate our mechanistic findings to treatment of human diseases

 

5 main publications

1. Iershov A, Nemazanyy I, Alkhoury C, Girard M, Barth E, Cagnard N, Montagner A, Chretien D, Rugarli E, Guillou H, Pende M, Panasyuk G The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARa. Nature Commun. 2019 Apr 5; 10(1):1566.

2. Patitucci C, Couchy G, Bagattin A, Cañeque T, de Reyniès A, Scoazec JY, Rodriguez R, Pontoglio M, Zucman-Rossi J, Pende M, Panasyuk G. Hepatocyte nuclear factor 1α suppresses steatosis-associated liver cancer by inhibiting PPARγ transcription. J Clin Invest. 2017 May 1;127(5):1873-1888.

3. Nemazanyy I, Montagnac G, Russell R, Guan KL, Pende M, Panasyuk G. Class III PI3K controls hepatic insulin receptor function on whole body glucose homeostasis by a retrograde signalling mechanism. Nature Comm. 2015 Sep; 6:8283.

4. Nemazanyy I, Blaauw B, Paolini C, Caillaud C, Protasi F, Mueller A, Proikas-Cezanne T, Russell RC, Guan KL, Nishino I, Sandri M, Pende M, Panasyuk G. Defects of Vps15 in skeletal muscles lead to autophagic vacuolar myopathy and lysosomal disease. EMBO Mol Med. 2013 Jun;5(6):870-90.

5. Panasyuk G, Girard M. Treatment of diseases associated with biliary system destruction, European patent EP18306343.7.

 

Five major original publications

  • Alkhoury C., Henneman N.F., Petrenko V., Shibayama Y., Segaloni A., Gadault A., Nemazanyy I., Le Guillou E., Wolide A.D., Antoniadou K., Tong X., Tamaru T., Ozawa T., Girard M., Hnia K., Lutter D., Dibner C., Panasyuk G. (2023). Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis. Nat Cell Biol. Jul;25(7):975-988. doi: 10.1038/s41556-023-01171-3. Epub 2023 Jul 6.
  • Shibayama Y., Alkhoury C., Nemazanyy I., F Henneman N., Cagnard N., Girard M., Atsumi T., Panasyuk G. (2022). Class 3 phosphoinositide 3-kinase promotes hepatic glucocorticoid receptor stability and transcriptional activity. Acta Physiol (Oxf). May;235(1):e13793. doi: 0.1111/apha.13793
  • lershov A., Nemazanyy I., Alkhoury C., Girard M., Barth E., Cagnard N., Montagner A., Chretien D., Rugarli E.I., Guillou H., Pende M., Panasyuk G. (2019)The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα. Nature Comm. 10(1): 1566. doi: 10.1038/s41467-019-09598-9
  • Niemir N., Rouvière L., Besse A., Vanier M., Dmytrus J., Marais T., Astord S., Puech J-P., Panasyuk G., Cooper J., Barkats M., Caillaud C. (2018). Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents pathology in Sandhoff disease mice. Human Mol. Gen. 27(6): 954-968. doi:10.1093/hmg/ddy012
  • Patitucci C., Couchy G., Bagattin A., Cañeque T., de Reyniès A., Scoazec J-Y., Rodriguez R., Pontoglio M., Zucman-Rossi J., Pende M., Panasyuk G. (2017). Hepatocyte nuclear factor 1α suppresses steatosis-associated liver cancer by inhibiting PPARγ transcription. J Clin Invest. 127(5): 1873-1888. doi: 10.1172/JCI90327

  • Complete list of publications on the following link: http://panasyuklab.fr/publications

    Dr. Ganna Panasyuk has obtained a PhD degree in Molecular biology from the Institute of Molecular biology and Genetics of National Academy of Sciences of Ukraine in Kyiv (Ukraine, 2006). In her graduate studies she was trained in the field of major growth regulator mTOR/PI3K/S6K signalling in the lab of Prof. Valeriy Filonenko (Institute of Molecular Biology and Genetics, Kyiv, Ukraine). It is through this graduate training and multiple collaborative visits to Ludwig Institute for Cancer Research in London, UK that her long-lasting interest in the cross-talk between metabolism and signal transduction was ignited. She has continued in postdoctoral studies in the lab of Prof. Ivan Gout at University College London in UK where she has discovered the novel splice form of mTOR kinase and demonstrated its relevance for cell proliferation.

    In 2009, she came to France to join the lab of Dr. Mario Pende at INSERM. This postdoctoral training has shaped her scientific interest in the mechanisms of metabolic control in physiology and its implication in human disease. She has won an INSERM tenure position in 2013 following a highly competitive international recruitment procedure to develop a research program at the Institute Necker Enfants Malades in Paris. In 2019, the professional achievements of Dr. Panasyuk have being recognized by DR2 promotion from INSERM. Dr. Panasyuk also holds a habilitation degree (HDR) from University Paris Descartes (2015) and is involved in scientific mentoring programs at INEM and different French universities.

    Permanent researcher
    Catherine Caillaud
    Professor Researcher
    +33 (0)1 71 39 69 74
    Dominique Debray
    Researcher
    Muriel Girard
    Professor Researcher
    +33 (0)1 40 61 53 44
    Ganna Panasyuk
    Researcher
    +33 (0)1 40 61 53 44
    Non permanent engineer
    Daryna Batechko
    -
    Alexis Gadault
    Engineer
    +33 (0)1 40 61 53 45
    Arianna Segaloni
    Engineer
    PhD
    Nathaniel Fathe Henneman
    PhD Student
    +33 (0)1 40 61 53 47
    Edouard Le Guillou
    PhD Student
    Visitor
    Ying Luo
    Post-Doctoral Researcher
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    Support(s)
    HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

    INEM - Organigramme