Manami Hara, D.D.S., Ph.D.

Identification and Characterization of the Cells that Define the Lineage that Gives Rise to the Pancreatic Beta Cell.

Research Summary

The overall goal of Dr. Hara’s research program is to identify and characterize the cells that define the lineage that gives rise to the pancreatic beta cell. She has generated a series of lines of transgenic mice expressing green fluorescent protein (GFP) and DsRed1 under the control of a series of transcription factors that characterize different cell types in the beta cell lineage. She is characterizing the pattern of gene expression in these genetically-tagged cells using expression profiling with Affymetrix Gene Chips and custom arrays. These studies may lead to the identification of the stem cell which gives rise to the pancreatic beta cell and open up new avenues for preventing and treating diabetes.

Selected Papers

Hara M, Alcoser SA, Qaadir A, Beiswenger KK, Cox NJ and Ehrmann DA. (2002). Insulin Resistance is attenuated in women with polycystic ovary syndrome with the Pro12Ala polymorphism in the PPARy gene. J Clin Endocrinol Metab 87: 772-775.

Ehrmann DA, Schwarz PEH, Hara M, Tang X, Horikawa Y, Imperial J, Bell GI, Cox NJ. (2002). Relationship of Calpain-10 Genotype to Phenotypic Features of Polycystic Ovary Syndrome. J Clin Endocrinol Metab 87:1669-1673.

Hara M, Wang X, Kawamura T, Bindokas VP, Dizon RF, Alcoser SY, Magnuson MA, Bell GI. (2003). Transgenic mice with green fluorescent protein-labeled pancreatic -cells. Am J Physiol Endocrinol Metab 284: E177-E183.

Treutelaar MK, Skidmore JM, Hara M, Zhang L, Simeon D, Martin DM, Burant CF. (2003). Nestin-lineage cells contribute to the microvasculature, but not endocrine cells of the islet. Diabetes 52:2503-2512.

Kojima H, Fujimiya M, Matsumura K, Nakahara T, Hara M, Chan L. (2004). Extrapancreatic insulin-producing cells in multiple organs in diabetes. Proc Natl Acad Sci 101: 2458-2463.

Reutrakul S, Hathout EH, Janner D, Hara M, Donfack J and Refetoff S. (2004). Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity and insulin resistance. Thyroid 14(4):311-9.

Alcoser YS, Hara M, Ehrmann AD. (2004). Association of the ARE polymorphism in PPP1R3 with hormonal and metabolic features of polycystic ovary syndrome. J Clin Endocrinol Metab 89(6):2973-6.

Hara M, Yin D, Dizon RF, Han M, Shen J, Chong AS, Bidokas VP. (2004). A mouse model for studying itrahepatic pancreatic islet transplantations. Transplantation 78(4):615-8.

Gunawardana SC, Hara M, Bell GI, Head WS, Magnuson MA and Piston DW. (2005). Imaging beta-cell development in real-time using pancreatic explants from mice with green flurescent protein-labeled pancreatic beta-cells. In Virto Cell Dev Anim 41: 7-11.

Terashima T, Kojima H, Fujimiya M, Matsumura K, Oi J, Hara M, Kashiwagi A, Kimura H, Yasuda H and Chan L. (2005). The fusion of bone marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy. Proc. Natl. Acad. Sci. 102: 12525-30.

Hara M, Noiseux N and Bindokas PV. (2005). High resolution optical imaging of infarction in intact organs. BioTechniques 39: 373-376.

Leung YM, Ahmed I, Sheu L, Tsushima RG, Diamant NE, Hara M and Gaisao HY. (2005). Electrophysiological characterization of pancreatic islet cells in the MIP-GFP mouse. Endocrinology 146: 4766-4775.

Yin D, Tao J, Shen J, Hara M, Lopez J, Kuznetsov A, Philipson LH, Chong AS. Liver ischemia contributes to early islet failuer following intraportal transplantation: Benefits of liver ischemic-preconditioning. Am J Transplant (in Press)