Anil Bhushan, PhD Assistant Professor Director, Islet Imaging Core (310) 206-5750 abhushan@mednet.ucla.edu

Dr Bhushan earned his PhD in Biophysics at University of California, Davis. He was a postdoctoral fellow at the Salk Institute of Biological Studies where he worked on TGF-beta signaling in the specification and patterning of endoderm. He subsequently worked at Institute Curié and Hospital Robert Debre in Paris on pancreatic development. The major goals of my laboratory are to understand the molecular mechanisms that govern beta cell formation and regeneration of pancreatic beta cells. An inadequate mass of functional beta cells results in diabetes mellitus, a metabolic disorders characterized by hyperglycaemia and defective metabolism of glucose. Therapeutic strategies involve restoring functional beta cell mass by exogenous replacement or transplantation of a source of beta cells such as embryonic stem cells derived beta cells or activation of endogenous regeneration of beta cells. Elucidation of the epigenetic network that regulates transcription during pancreatic developmental and regeneration will provide the blueprint by which the extra-cellular cues are interpreted at the nuclear level by the transcription machinery to select the repertoire of beta cell-specific genes. Such a blueprint will inform us on how to direct stem cells to beta cell fate in vitro and allow us to devise pharmacological interventions toward selective manipulation of gene expression to promote regeneration of beta cell mass. Furthermore, generation of animal models of diabetes and strategies to develop novel cellular therapies for diabetes can enable and test outcomes for candidate therapeutic approaches. While the interest of the laboratory is on beta cell formation and regeneration, a number of molecular components of the epigenetic network we study are involved not only in the formation of diverse organs but they also contribute to the development of cancer. Close proximity with these groups within the center should generate molecular tools, genetic resources, and experience that will greatly enhance the efforts of investigators in this center to assess and experimentally manipulate the stem cell and regenerative based research.

Anil Bhushan Publications

1. Anil Bhushan, Jean Paul Thiery, Paul Czernichow, Saverio Belluci and Raphael Scharfmann. FGF10 is essential for maintaining the proliferative capacity of progenitor cells during early pancreatic organogenesis. Development 2001, 128 (24), 5109-5117.
Abstract

2. Senta Georgia and Anil Bhushan. ß-cell replication is the primary mechanism for maintaining postnatal ß cell mass. Journal of Clinical Investigation 2004, 114: 963-968.
Abstract

3. Senta Georgia and Anil Bhushan. p27 regulates the transition of beta cells from quiescence to proliferation Diabetes 2006, (in press).
Abstract: Pending

4. Senta Georgia, Min Li, Pumin Zhang and Anil Bhushan. p57 and Hes1 coordinate endocrine differentiation with self-renewal of pancreatic progenitors Developmental Biology 2006, [Epub ahead of print].
Abstract

5. Senta Georgia and Anil Bhushan Cell cycle regulation and beta cells in Islet ß-Cell Growth Factors, Lander Biosciences 2006, (in press).
Abstract: Pending

6. Juris J. Meier, Anil Bhushan, Peter C. Butler The potential for stem cell therapy in diabetes. Pediatr Res. 2006, 59(4 Pt 2): 65R-73R.
Abstract

7. Xiuli Wang, Shundi Ge, Ignacio Gonzalez , George McNamara, C. Barth Rountree, Kenny Kezhe Xi, Grace Huang, Anil Bhushan, Gay M. Crooks. Formation of Pancreatic Duct Epithelium from Bone Marrow During Neonatal Development Stem Cells 2006, 24(2):307-14.
Abstract

8. Juris J. Meier, Anil Bhushan, Alexandra E. Butler, Robert A. Rizza, Peter C. Butler Sustained beta-cell apoptosis in patients with long-standing type 1diabetes: Indirect evidence for islet regeneration? Diabetologia 2005, 48(11):2221-8
Abstract

Selected peer-reviewed publications

Prescott B, Renugopalakrisnan V, Glimcher MJ, Bhushan A, Thomas GJ, Jr. (1986). A Raman spectroscopic study of hen egg yolk phosvitin: Structures in solution and in the solid state. Biochemistry 25: 2792-2798.

Bhushan A, McNamee M. (1990). Differential scanning calorimetry and Fourier transform infrared analysis of lipid-protein interactions involving the nicotinic acetylcholine receptor. Biochimica Biophysica Acta 1027: 93-101.

Bhushan A, McNamee M. (1993). Correlation of phospholipid structure with functional effects of the nicotinic acetylcholine receptor: A modulatory role for phosphatidic acid. Biophys. J. 64:716-723.

Bhushan A, Lin HY, Lodish H, Kitner C (1994). The TGF-beta II receptor can replace the activin type II receptor in inducing mesoderm in Xenopus embryos. Mol. Cell. Biol. 14: 4280-4285.

Bhushan A, Chen Y, Vale W. (1997). Smad8 mediates the signaling of the ALK-2 receptor serine kinase. Proc. Natl. Acad. Sci. USA 94: 12938-12943.

Bhushan A, Chen Y, Vale W. (1998). Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos. Dev. Biol. 200: 260-268.

Bach I, Rodriguez-Esteban C, Carriere C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisua Belmonte JC, Rosenfeld MG. (1999). RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nature Genetics 22 (4): 394-399.

Bhushan A, Thiery JP, Czernichow P, Belluci S, Scharfmann R. FGF10 is essential for maintaining the proliferative capacity of progenitor cells during early pancreatic organogenesis. Development 2001, 128 (24), 5109-5117.

Georgia S, Bhushan A. (2004). ß cell replication is the primary mechanism for maintaining postnatal ß cell mass. Journal of Clinical Investigation 114: 963-968.

Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. (2005) Sustained beta-cell apoptosis in patients with long-standing type 1diabetes: Indirect evidence for islet regeneration? Diabetologia 48(11):2221-8.

Wang X, Ge S, Gonzalez I, McNamara G, Rountree CB, Xi KK, Huang G, Bhushan A, Crooks GM. (2005) Formation of Pancreatic Duct Epithelium from Bone Marrow During Neonatal Development Stem Cells 24(2): 307-14.

Meier JJ, Bhushan A, Butler PC. The potential for stem cell therapy in diabetes. Pediatr Res. (2006) 59(4 Pt 2): 65R-73R.

Georgia S, Li M, Zhang P, Bhushan A. (2006) p57 and Hes1 coordinate endocrine differentiation with self-renewal of pancreatic progenitors Developmental Biology 298 22 - 31.

Georgia S, Bhushan A. (2006) p27 regulates the transition of beta cells from quiescence to proliferation Diabetes 55(11): 2950-6

Georgia S, Bhushan A. Cell cycle regulation and beta cells in Islet Beta Cell Growth Factors, Lander Biosciences 2006 ISBN: 1-58706-104-X

Butler AE, Huang CJ, Rao PN, Bhushan A, Hogan WJ, Rizza RA, Butler PC. (2007) Hematopoietic Stem Cells Derived from Adult Donors are Not a Source of Pancreatic Beta Cells in Adult Non Diabetic Humans Diabetes 10.2337/db06-1385

Zhong L, Georgia S, Tschen S, Nakayama K, Nakayama K, Bhushan A. (2007) Skp2-mediated p27 degradation plays an essential role in the growth and adaptive expansion of pancreatic beta cells Journal of Clinical Investigation 117 (10) :2869-76

Butler PC, Meier JJ, Butler AE, Bhushan A. (2007) Beta cell replication in disease and normal physiology Nat Clin Pract Endocrinol Metab 3(11):758-68

Dhawan S, Georgia S, Bhushan A. (2007) Formation and regeneration of the endocrine pancreas Current Opinions in Cell Biology 19(6):634-45.

Juris J. Meier, Alexandra E. Butler, Yoshifumi Saisho, Travis Monchamp, Ryan Galasso, Anil Bhushan, Robert A. Rizza, Peter C. Butler (2008) Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans Diabetes (online March 11)