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	2005 Fellow			Tatiana Hochgreb, Ph.D. Laboratory of Marianne Bronner-Fraser, Ph.D. Division of Biology California Institute of Technology Mail Code 139-74 1200 E. California Blvd. Pasadena, CA 91125 Phone: (626) 395-3359 Fax: (626) 449-8599 Email: tatiana.hochgreb@caltech.edu

Country: Brazil

Field: Regeneration of beta-cell in zebrafish

Research Interest: Disturbed beta-cell homeostasis and increased cell death are recurrent features of diabetes. As such, there is great interest in understanding how pancreatic islets may regenerate, since this knowledge may lead to therapies to restore normal beta-cell numbers and thus, normal metabolism. A variety of studies have shown that beta-cells can regenerate, and that mechanisms used during embryonic development of pancreas are recapitulated in this process. We propose to establish a zebrafish model of pancreatic islet injury to study beta-cell regeneration, because it provides, through forward genetics, the tools to perform large-scale screening studies. In this case, identification of novel important genes and pathways does not depend on preconceived ideas or models, potentially advancing the comprehension of pancreatic islet regeneration. To reproduce a diabetic state in the zebrafish, so that we can subsequently monitor the rates of beta-cell regeneration, we will damage insulin-producing cells by either chemical or genetic approaches. As such, the proposed study will significantly contribute to expand the set of tools currently available in diabetes research, by making the zebrafish model feasible for studies on diabetes and regeneration of beta-cells. Additionally, we will characterize the mechanisms involved in the regeneration of pancreatic beta-cells in the zebrafish. We expect that these experiments will critically contribute to advance the comprehension of the regeneration of pancreatic beta-cells, and eventually may help to develop therapies capable of restoring normal beta-cell numbers in the diabetic patient.