Contact info

Dr Mathieu Laplante
Facult� de m�decine, Universit� Laval
Centre de recherche de l'Institut universitaire de cardiologie et pneumologie de Qu�bec (CRIUCPQ)
2725 ch. Ste-Foy � Room Y3120
Quebec City, QC G1V 4G5

Tel: 1-418-656-8711, ext. 3972
Fax: 1-418-656-4940
E-mail: [email protected]

Link to Mathieu Laplante Lab webpage

Research keywords

Mathieu Laplante was trained in the laboratory of Yves Deshaies at Laval University where he obtained a PhD degree in 2007. The objective of his work was to improve the understanding of the mechanisms by which PPARg agonists modulate white adipose tissue distribution. After getting his degree, he joined the laboratory of David M Sabatini at the Whitehead Institute of Biomedical research, a research center affiliated to the Massachusetts Institute of Technology (MIT) in Boston. From 2007 to 2011, he worked on the identification and the characterization of a new mTOR-interacting protein named DEPTOR. In 2011, he was recruited as assistant Professor by the Department of Medicine at Laval University.

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1) Laplante M, Horvat S, et al., DEPTOR cell-autonomously promote adipogenesis and is overexpressed in obesity. Cell Metab, 8;16(2):202-12, 2012.

In this paper, we identify DEP domain containing mTOR-interacting protein (DEPTOR) as a positive regulator of adipogenesis that is associated with obesity. Using a doxycycline inducible mouse model for Deptor overexpression, we show that Deptor promotes adipose tissue expansion in vivo. DEPTOR expression is elevated in adipose tissue of obese humans and strongly correlates with the degree of obesity. We show that DEPTOR is induced during adipogenesis and that its overexpression cell-autonomously promotes adipogenesis. These results establish DEPTOR as a physiological regulator of adipogenesis.

2) Peterson TR, Laplante M, et al., DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival, Cell, 137(5): 873-886, 2009.

In this paper, we identify DEPTOR as a new protein interacting with mTOR. DEPTOR negatively regulates the action of mTOR, a protein playing key roles in many human diseases. We show that DEPTOR expression is low is most cancers. Surprisingly, DEPTOR is highly expressed in a subset of multiple myelomas (MM). We show that MM use DEPTOR to promote cell survival and we show that the reduction in DEPTOR expression causes the death of these cancer cells. These results generate hope for the treatment of MM.

3) Caron A, Baraboi ED, Laplante M*, Richard D* (*corresponding authors), DEP-domain containing mTOR-interacting protein in the rat brain: distribution of expression and potential implication. J Comp Neurol, epub, 2014.

In this study, we mapped the expression of DEPTOR in the rat brain and observed that it is expressed in regions of the brain involved in the control of energy balance. We also show that DEPTOR expression is elevated in the hypothalamus of obese animals, suggesting that DEPTOR could represent a target to improve energy balance in obesity.

4) Laplante M and Sabatini DM, mTOR signaling in growth control and disease, Cell, 13;149(2):274-93, 2012.

In this article, we reviewed the knowledge of the mTOR signaling pathway and discussed about its implications in human diseases. This review covers various aspects of mTOR biology and rapidly became a reference.

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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.

Study of the mechanisms linking obesity to its metabolic complications. 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.

Study of the implication of MTOR signaling in health and diseases. 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. Studies indicate that these complexes are highly active in many cancers and in obesity. 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, to define the transcriptional signature of that association and to determine the implication of these discoveries in health and diseases.