Sabine Colnot
  • E-mail :[email]
  • Phone : +33 1 44274005
  • Location : Paris, France
Last update 2020-01-22 16:48:17.939

Sabine Colnot PhD, HDR, Research Director DR2 INSERM

Course and current status

Dr Sabine Colnot, PhD, graduated as a medical lab technician in 1982. She headed a clinical laboratory with « Doctors without Borders » in 1988 in Thailand, and turned to academic research at French National Institute for Health and Medical Research in Paris, working as a self-learner lab engineer. After completing her PhD in 1999, she has been a post-doctoral scientist with Dr Perret at Cochin Institute in Paris, got an academic position in 2003, and heads her research group since 2006.

Since 2019, she leads her research team "Oncogenic functions of beta-catenin signaling in the liver" at the Centre de Recherche des Cordeliers in Paris (INSERM UMRS1138).

Scientific summary

New targets of β-catenin in liver primary cancers

Hepatocellular carcinoma (HCC) is the most frequent liver primitive cancer, and the second cause of death by cancer worldwide. It is associated with major risk factors, such as B and C viral hepatitis, alcohol abuse and metabolic syndrome. Its poor prognostic is due to a lack of therapeutic options, consisting in a first-line surgical tumor removal, and in administration of sorafenib, increasing life expectancy of only several months. Two decades ago, Christine Perret’s lab found that 15 to 40% of the HCCs depend on activating mutations of CTNNB1 encoding β-catenin (CTNNB1-mut) (de la Coste, PNAS 1998). These HCCs constitute a particular class of HCCs, with peculiar phenotypic traits.

We generated transgenic murine models of hepatic β-catenin activation/inactivation, thereby showing that β-catenin plays multiple roles in liver physiopathology: i) an aberrant β-catenin activation in the adult liver is an oncogenic event (Colnot et al., PNAS 2004); ii) a physiological Wnt signaling in a restricted area of adult hepatocytes is responsible for the so-called zonation of liver metabolic functions (Benhamouche et al., Dev Cell 2006); iii) during embryogenesis, β-catenin aberrant signaling engages hepatic progenitors towards a biliary fate (Decaens et al., Hepatology 2008).

My research group then focused on β-catenin-induced transcriptional program, showing that it elicits the expression of genes involved in proliferation (Torre et al., J Hepatol 2011) and in metabolism (Gougelet at al., Hepatology 2014). We also brought the proof-of-concept that a miRNA-targeted approach is anti-tumoral in a context of β-catenin-activated HCC (Gougelet et al., Gut 2016).

More recently, we showed that β-catenin-activated HCC have specific metabolic needs. They are addicted to fatty acids to fuel their energetic needs (Senni et al., Gut 2019). They use dietary choline to enhance phospholipid synthesis and to overmethylate DNA, both being involved in cancer cell proliferation. β-catenin-activated HCCs can specifically detected by fluorocholine positron emission tomography (Gougelet, Sartor, Senni et al., Gastroenterology 2019)

Our lab goes further in characterizing in vivo key steps of liver carcinogenesis, at the molecular and cellular levels, focusing on epigenetic and metabolic events involved in this process, with the goal to propose new therapeutic targets for β-catenin-activated HCCs, that will be tested in our preclinical murine models.

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