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Mathieu Laplante Laboratory

PROJECTS

STUDY OF THE MOLECULAR MECHANISMS REGULATING ADIPOGENESIS

 

Obesity is defined as the excessive accumulation of adipose tissue and is an important cause of death worldwide. The prevalence of obesity is increasing in many countries and authorities view this condition as one of the most serious public health problems. Although changes in lifestyle are responsible for the increase in incidence of obesity, heritability studies provide evidence for a substantial genetic contribution to obesity risk. This indicates that humans are not equally susceptible to weight gain and that interaction between genes and environment plays fundamental roles in obesity development. Because diet and physical activity have shown limited long-term success in reducing obesity, the improvement of our understanding of the molecular mechanisms regulating food consumption and energy storage could help the development of new tools to treat obesity and its related diseases.
 
Key questions :    
  • What are the factors that define the identity of preadipocytes and their adipogenic potential?
  • Is there any factors secreted by enlarged adipocytes that help the recrutment of new fat cells during the development of obesity? 
  • Is it possible to treat obesity and its related complications by modifying the adipocyte life cycle?
STUDY OF THE MECHANISMS LINKING OBESITY TO ITS METABOLIC COMPLICATIONS
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Obesity caused by the imbalance of the energy balance severely impairs normal liver metabolism. Ectopic fat accumulation and chronic inflammation observed in obese represent some factors contributing to the deterioration of glucose metabolism and lipid in this tissue. Although our understanding of the mechanisms involved in the development of metabolic diseases associated with obesity has greatly improved in recent decades, important questions are still without answer. For example, how the liver communicates his physical and metabolic state to other tissues is still not well understood. In recent years, we have observed that a protein called DEPTOR could play roles in the control of hepatic metabolism in response to nutritional changes. With the use of transgenic mouse models allowing the deletion or the overexpression of DEPTOR, we try to understand the role of this specific protein in hepatic metabolism, and its implication in the regulation of liver function in obesity.
Key questions :    
  • What is the role of DEPTOR in the regulation of liver metabolism in leanness and obesity?
  • Could it be possible to modulate hepatic metabolism by manipulating DEPTOR expression?
  • Does the liver secrete specific proteins to inform peripheral tissues of its metabolic state?                  
STUDY OF CELL SIGNALING IN CANCER
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The mechanistic target of rapamycin (mTOR) is a kinase that plays a crucial role in controlling cell growth and metabolism. mTOR is found in two complexes called mTOR complex 1 and 2 (mTORC1 and mTORC2). In response to nutrients and growth factors, these complexes activate several anabolic processes including the synthesis of proteins and lipids. Several oncogenes and tumor suppressors are known to control the action of mTORC1/2. Studies indicate that these complexes are highly active in many cancers. In recent years, research groups have observed that in addition to controlling protein synthesis, mTOR pathway profoundly affects gene transcription by directly modulating the activity of several transcription factors. The objective of our work is to identify new transcription factors whose activity is modulated by mTOR and to define the transcriptional signature of that association.

 
Key questions :   
  • Does mTOR regulate the action of transcription factors that have not been identified so far?
  • Can we identify these new transcription factors?     
  • Can these discoveries be exploited to develop new therapeutic avenues for the treatment of cancer?                 
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