Graduate School of Medical Sciences

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Arleen Rifkind

Professor

Dr. Rifkind has had a long standing research interest in the molecular mechanisms by which the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) produces its toxic effects and in the role of cytochrome P4501A induction in those effects. At sublethal doses, TCDD is carcinogenic and causes a wasting syndrome and defects in cardiac contraction. Uniquely, TCDD produces all of its toxic and biochemical effects by activation of a cellular receptor, the aryl hydrocarbon receptor (AhR). The AhR is increasingly being recognized to have important regulatory roles in normal physiologic processes as well in mediating toxicity of TCDD and related aromatic hydrocarbons. AhR activation by TCDD elicits transcriptional increases in cytochrome P450 (CYP) enzymes in the CYP1A family as well as TCDD toxicities. Using the chick embryo as a model, Dr. Rifkind's group discovered that human and chick CYP1A2 are highly active epoxygenases for the membrane lipid, arachidonic acid, indicating that CYP1A may exert biologic effects via the metabolism of endogenous substances as well as foreign chemicals. 

Dr. Rifkind's laboratory is currently investigating transcriptional and posttranscriptional effects of AhR activation and CYP1A induction resulting in dysregulation of cell signaling pathways governing gluconeogenesis and lipid metabolism (i.e. the Akt, AMPK and PGC1 pathways) and in disturbed mitochondrial function. Her group is using TCDD as a tool to probe the AhR. Molecular and biochemical approaches in primary hepatocyte and cardiac myocyte cultures and in the chick embryo in ovo, are being used to study effects of AhR activation on energy production and nutrient homeostasis in liver and heart. Effects of TCDD resemble pathologic changes in cancer, heart disease, diabetes mellitus, and wasting syndromes, major human diseases. Dr. Rifkind's research seeks to identify new pharmacologic targets for those conditions as well as regulatory roles of the AhR in energy metabolism.

Research Topics

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Weill Cornell Medicine
Graduate School of Medical Sciences
1300 York Ave. Box 65 New York, NY 10065 Phone: (212) 746-6565 Fax: (212) 746-5981