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Genetic regulation of fat storage Obesity is the leading cause of type-2 diabetes, cardiovascular diseases, and hypertension — the so-called Metabolic Syndrome. Excessive accumulation of body fat can be attributed to both genetic and environmental factors. The goal of our laboratory is to identify genetic pathways and molecular mechanisms that regulate fat storage in metazoans. Although monogenic obesity disorders, such as leptin deficiency, have been identified, obesity in the general population probably has a polygenic origin. It is therefore imperative to identify additional components of known and novel signaling pathways that regulate fat storage. This will provide new therapeutic targets for the treatment of obesity and diabetes and new candidates for whole genome linkage scans for single nucleotide polymorphisms that are associated with obesity. Our research is based on the hypothesis that an ancient signaling axis is conserved from the nematode C. elegans to human: nutrient sensation by ciliated sensory neurons triggers neuroendocrine signals secretion and these in turn modulate metabolism in fat storage tissues. Disruption of such signaling axis, for example, through mutation in genes required for ciliated neuron integrity such as bbs/Bardet-Biedl syndrome and tubby, causes excessive fat accumulation in C. elegans and mammals. Our future effort will be devoted to answering the following questions: (1) how are nutrient levels detected and what are the neuroendocrine signals that modulate fat storage in peripheral tissues; (2) what are the neuroendocrine signal transducers in target tissues; (3) how is the size of intracellular lipid storage droplet determined? We will address these questions using genetics, biochemistry, DNA microarray technology, fluorescence and electron microscopy in tissue culture systems and in the nematode C. elegans. Academic Appointment: Assistant Professor, Department of Molecular & Integrative Physiology, The University of Kansas School of Medicine Selected publications
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