Anil Bhushan, PhD
Professor
Diabetes Center
School of Medicine

Senescent beta cells can remodel the islet environment in a paracrine manner by promoting bystander senescence and immune surveillance. We have identified key immune cells that can selectively eliminated senescent beta cells to halted progression of beta cell destruction prevent T1D in mouse models. We use a combination of mouse models of autoimmunity, humanized mouse models transplanted with senescent cells to investigate the underlying mechanism by which tissue senescent cells contribute to the development of the various diseases. We also now use utilize immune modulatory targets to identify new drugs that specifically eliminate tissue senescent human cells and develop an in vivo humanized mouse model to test efficacy of drugs to clear human senescent cells.

• mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes.
  The Journal of clinical investigation 2019 Jaafar R, Tran S, Shah AN, Sun G, Valdearcos M, Marchetti P, Masini M, Swisa A, Giacometti S, Bernal-Mizrachi E, Matveyenko A, Hebrok M, Dor Y, Rutter GA, Koliwad SK, Bhushan A
• The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β-Cell Function.
  Diabetes 2019 Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R
• Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells.
  Nature cell biology 2019 Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M
• Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells.
  Nature cell biology 2019 Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M
• Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.
  Diabetes 2018 Cyphert HA, Walker EM, Hang Y, Dhawan S, Haliyur R, Bonatakis L, Avrahami D, Brissova M, Kaestner KH, Bhushan A, Powers AC, Stein R
• Cyclin D2 is sufficient to drive β cell self-renewal and regeneration.
  Cell cycle (Georgetown, Tex.) 2017 Tschen SI, Zeng C, Field L, Dhawan S, Bhushan A, Georgia S
• β Cells led astray by transcription factors and the company they keep.
  The Journal of clinical investigation 2016 Thompson P, Bhushan A
• Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication.
  Diabetes 2016 Dhawan S, Dirice E, Kulkarni RN, Bhushan A
• DNA methylation directs functional maturation of pancreatic β cells.
  The Journal of clinical investigation 2015 Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A
• Human β-cell proliferation and intracellular signaling: part 3.
  Diabetes 2015 Stewart AF, Hussain MA, García-Ocaña A, Vasavada RC, Bhushan A, Bernal-Mizrachi E, Kulkarni RN
• Combined modulation of polycomb and trithorax genes rejuvenates β cell replication.
  The Journal of clinical investigation 2013 Zhou JX, Dhawan S, Fu H, Snyder E, Bottino R, Kundu S, Kim SK, Bhushan A
• The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation.
  The EMBO journal 2013 Kartikasari AE, Zhou JX, Kanji MS, Chan DN, Sinha A, Grapin-Botton A, Magnuson MA, Lowry WE, Bhushan A
• DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis.
  Genes & development 2013 Georgia S, Kanji M, Bhushan A
• Dicer1 is required to repress neuronal fate during endocrine cell maturation.
  Diabetes 2013 Kanji MS, Martin MG, Bhushan A
• Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming.
  Genes & development 2011 Papizan JB, Singer RA, Tschen SI, Dhawan S, Friel JM, Hipkens SB, Magnuson MA, Bhushan A, Sussel L
• Skp2 is required for incretin hormone-mediated β-cell proliferation.
  Molecular endocrinology (Baltimore, Md.) 2011 Tschen SI, Georgia S, Dhawan S, Bhushan A
• Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx.
  Developmental cell 2011 Dhawan S, Georgia S, Tschen SI, Fan G, Bhushan A
• Pregnancy hormones boost beta cells via serotonin.
  Nature medicine 2010 Georgia S, Bhushan A
• Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.
  American journal of physiology. Endocrinology and metabolism 2010 Matveyenko AV, Georgia S, Bhushan A, Butler PC
• Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents.
  Diabetes 2010 Georgia S, Hinault C, Kawamori D, Hu J, Meyer J, Kanji M, Bhushan A, Kulkarni RN
• Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation.
  Genes & development 2009 Dhawan S, Tschen SI, Bhushan A
• Age-dependent decline in beta-cell proliferation restricts the capacity of beta-cell regeneration in mice.
  Diabetes 2009 Tschen SI, Dhawan S, Gurlo T, Bhushan A
• Deletion of the mitochondrial flavoprotein apoptosis inducing factor (AIF) induces beta-cell apoptosis and impairs beta-cell mass.
  PloS one 2009 Schulthess FT, Katz S, Ardestani A, Kawahira H, Georgia S, Bosco D, Bhushan A, Maedler K
• Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans.
  Diabetes 2008 Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, Rizza RA, Butler PC
• Formation and regeneration of the endocrine pancreas.
  Current opinion in cell biology 2007 Dhawan S, Georgia S, Bhushan A
• The replication of beta cells in normal physiology, in disease and for therapy.
  Nature clinical practice. Endocrinology & metabolism 2007 Butler PC, Meier JJ, Butler AE, Bhushan A
• Essential role of Skp2-mediated p27 degradation in growth and adaptive expansion of pancreatic beta cells.
  The Journal of clinical investigation 2007 Zhong L, Georgia S, Tschen SI, Nakayama K, Nakayama K, Bhushan A
• Hematopoietic stem cells derived from adult donors are not a source of pancreatic beta-cells in adult nondiabetic humans.
  Diabetes 2007 Butler AE, Huang A, Rao PN, Bhushan A, Hogan WJ, Rizza RA, Butler PC
• p27 Regulates the transition of beta-cells from quiescence to proliferation.
  Diabetes 2006 Georgia S, Bhushan A
• p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors.
  Developmental biology 2006 Georgia S, Soliz R, Li M, Zhang P, Bhushan A
• The potential for stem cell therapy in diabetes.
  Pediatric research 2006 Meier JJ, Bhushan A, Butler PC
• Formation of pancreatic duct epithelium from bone marrow during neonatal development.
  Stem cells (Dayton, Ohio) 2006 Wang X, Ge S, Gonzalez I, McNamara G, Rountree CB, Xi KK, Huang G, Bhushan A, Crooks GM
• Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass.
  The Journal of clinical investigation 2004 Georgia S, Bhushan A
• Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis.
  Development (Cambridge, England) 2001 Bhushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R
• Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos.
  Developmental biology 1998 Bhushan A, Chen Y, Vale W
• Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase.
  Proceedings of the National Academy of Sciences of the United States of America 1997 Chen Y, Bhushan A, Vale W
• The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.
  Molecular and cellular biology 1994 Bhushan A, Lin HY, Lodish HF, Kintner CR