研究领域

The overarching goal of my research is to determine how environmental factors (both natural and anthropogenic) shape metabolic phenotypes in teleost fish across their life-cycle and between generations. The lab uses an integrative approach to characterize metabolic phenotypes at multiple levels of biological organisation, ranging from organismal to the cellular and molecular level approaches. A recent focus lies in determining the role of how epigenetic molecular mechansisms, especially microRNAs, regulate fish metabolism in response to environmental stimuli, both within the life-cycle of fish and across generations. Experimental models include rainbow trout and zebrafish, which allow to extend basic research to aquaculture and aquatic toxicology.

I principally use two teleost research models, zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) to comparatively study energy metabolism, using an integrated approach. This approach covers molecular, cellular and organismal aspects of energy metabolism, all of which integratively form the metabolic phenotype. A current research focus lies on the elucidation of epigenetic origins of metabolic phenotypes across ontogeny and generations, which in contrast to mammalian research models remains largely uncharacterized in lower vertebrates. In addition to providing comparative insight into epigenetic mechanisms governing the metabolic phenotype, the study of epigenetic mechanisms in fish models is especially applicable to three major areas addressed under this framework, which are outlined below. 1) Aquaculture In addition to being a valuable research model in the comparative physiology of metabolism, rainbow trout are the most important aquaculture species in Ontario. Following the recent sequencing of the rainbow trout genome, novel possibilities exist to address regulation and function of context-dependent epigenetic mechanisms in the metabolic phenotype. Focusing primarily on microRNAs, I am interested in how these molecular epigenetic mechanisms contribute to the metabolic phenotype in rainbow trout across ontogeny and at different levels of biological organization. In addition to providing insight into the evolution of microRNA mediated metabolic networks and function, the elucidation of these mechanisms will provide novel insight into the contribution of epigenetic mechanisms to rainbow trout specific phenotypes relevant to aquaculture. Examples include the implication of epigenetic mechanisms in mediating acute and sustained metabolic and growth effects of plant-based diets and the potential implication of epigenetic mechanisms in nutritional programming approaches. 2) Ecotoxicology Principally using the zebrafish model, Danio rerio, I am interested in the role of endocrine disrupting chemicals on the metabolic phenotype across ontogeny and generations either at baseline or in conjunction with environmental stressors experienced across ontogeny and generations. This represents an environmentally realistic scenario, as contaminants are subject to temporal variation due to regulation and continuing emergence of novel aquatic environments. A principal goal is to gain insight into germ-line dependent epigenetic mechanisms (principally DNA methylation) in the emergence of these phenotypes, and to develop epigenetic markers as improved prediction tools for EDC and aquatic contaminant exposure. 3) Teleost fish as models for metabolic disease Zebrafish are increasingly used as model systems for disease including metabolic disease. Taking advantage of this model, a specific research interest lies in the elucidation of transgenerational interaction of non-exclusive biological hypothesis of metabolic disease. A principal aim is to gain understanding of the integration of the three major biological hypothesis across ontogeny and generations in the emergence of metabolic disease: (1) The developmental origin of disease hypothesis ('Barker hypothesis') (2) the contribution of environmental endocrine disrupting chemicals ('obesogen hypothesis') (3) nutritional factors ('life-style hypothesis') This approach is aimed to gain insight into novel epigenetic determinants and the identification of novel molecular drug targets for metabolic disease.

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Mennigen, JA. Micromanaging metabolism: MicroRNAs in teleost fish. Comp Biochem Physiol B Biochem Mol Biol. pii: S1096-4959(15)00160-8.​ Geurden I, Mennigen JA, Plagnes-Juan E, Veron V, Cerezo T, Mazurais D, Zambonino-Infante J, Gatesoupe J, Skiba-Cassy S, Panserat S. 2014. High or low dietary carbohydrate:protein ratios during first-feeding affect glucose metabolism and intestinal microbiota in juvenile rainbow trout. Journal of Experimental Biology, 217:3396-406. Mennigen JA, Martyniuk CJ, Seiliez I, Panserat, S. Skiba-Cassy, S. Metabolic consequences of miRNA-122 inhibition in rainbow trout (Oncorhynchus mykiss). 2014. BMC Genomics, 15:70. Mennigen JA, Skiba S, Panserat S. Ontogenesis of expression of metabolic genes and microRNAs in of rainbow trout alevins during the transition from endogenous to exogenous feeding. 2012. Journal of Experimental Biology, 216:1597-1608. Mennigen JA, Panserat S, Larquier M, Plagnes-Juan E, Medale F, Seiliez I Skiba-Cassy S. Postprandial regulation of hepatic microRNAs predicted to target the insulin pathway in rainbow trout. 2012. PLoS One, 7:e38604. Mennigen JA, Sassine J, Trudeau VL, Moon TW. Effects of waterborne fluoxetine on food intake, weight and energy metabolism parameters in goldfish, Carassius auratus. 2010. Aquatic Toxicology, 100:128-137. Mennigen JA, Harris EA, Chang JP, Trudeau VL, Moon TW. 2009. The effect of fluoxetine on food intake and weight gain in female goldfish. Regulatory Peptides, 155:99-104.