Anil Bhushan • UCSF Profiles

Anil Bhushan, PhD

Title(s)	Professor, Diabetes Center
School	School of Medicine
Address	513 Parnassus Ave, HSW San Francisco CA 94143
Phone	415-502-3295
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Biography

Education and Training

Salk Institute, La Jolla, CA	Postdoctoral	1999	Development Biology
UCDavis, Davis CA	PhD	1992	Biochemistry and Biophysics
INSERM, Paris, France		2001	Diabetes

Overview

The long-term goal of my research is to understand the role of tissue secretory senescent cells in aging, autoimmunity and metabolic diseases. Our recent discovery shows that pancreatic beta cells acquire a secretome during T1D in mice and human and exhibit many non-cell autonomous properties. 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.

Interests

Senescence, autoimmunity, metabolic diseases, immune surveillance

Websites

Lab Web site

Research

Research Activities and Funding

Modulating the senescence secretome to block progression of T1D
NIH R01DK118099Jan 1, 2020 - Dec 31, 2023
Role: Principal Investigator

Targeting Senescence for Biomarkers and Therapeutics
NIH R01DK121794Jul 1, 2019 - Jun 30, 2022
Role: Principal Investigator

Mechanisms of beta cell maturation
NIH R01DK108666Sep 30, 2015 - Jul 31, 2019
Role: Co-Principal Investigator

Polycomb genes regulation of beta cell regeneration
NIH R01DK080996Mar 1, 2008 - Apr 30, 2018
Role: Principal Investigator

Cell Cycle Control Of Beta Cell Mass
NIH R01DK068763Jul 5, 2004 - Jun 30, 2016
Role: Principal Investigator

SPECIFICITY OF ACTIVIN SIGNALING THROUGH TYPE I RECEPTOR
NIH F32HD007969Sep 9, 1995
Role: Principal Investigator

ORNG Applications

Featured Publications

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Bibliographic

Publications

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.

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The Transcription Factor YY1 Is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-Cells. Diabetes. 2022 Aug 01; 71(8):1694-1705. Martins Peçanha FL, Jaafar R, Werneck-de-Castro JP, Apostolopolou CC, Bhushan A, Bernal-Mizrachi E. PMID: 35594378.

View in: PubMed Mentions: Fields:
End Endocrinology
Translation:Humans Animals Cells
Uncovering immune and senescent cell interactions in disease. Med (N Y). 2021 08 13; 2(8):895-898. Bhushan A. PMID: 35590165.

View in: PubMed Mentions:
Invariant Natural Killer T cells coordinate removal of senescent cells. Med (N Y). 2021 08 13; 2(8):938-950. Arora S, Thompson PJ, Wang Y, Bhattacharyya A, Apostolopoulou H, Hatano R, Naikawadi RP, Shah A, Wolters PJ, Koliwad S, Bhattacharya M, Bhushan A. PMID: 34617070; PMCID: PMC8491998.

View in: PubMed Mentions: 3 Translation:Animals Cells
BET Proteins Are Required for Transcriptional Activation of the Senescent Islet Cell Secretome in Type 1 Diabetes. Int J Mol Sci. 2019 Sep 26; 20(19). Thompson PJ, Shah A, Apostolopolou H, Bhushan A. PMID: 31561444; PMCID: PMC6801956.

View in: PubMed Mentions: 6 Fields:
Bio Biochemistry Che Chemistry Mol Molecular Biology
Translation:Humans Animals Cells
mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes. J Clin Invest. 2019 07 02; 129(10):4124-4137. 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. PMID: 31265435; PMCID: PMC6763225.

View in: PubMed Mentions: 32 Fields:
Med Medicine (General)
Translation:Animals Cells
The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β-Cell Function. Diabetes. 2019 09; 68(9):1806-1818. Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R. PMID: 31201281; PMCID: PMC6702633.

View in: PubMed Mentions: 10 Fields:
End Endocrinology
Translation:Animals Cells
Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells. Nat Cell Biol. 2019 06; 21(6):792. 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. PMID: 30914825.

View in: PubMed Mentions: 1 Fields:
Cel Cell Biology
Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes. Cell Metab. 2019 05 07; 29(5):1045-1060.e10. Thompson PJ, Shah A, Ntranos V, Van Gool F, Atkinson M, Bhushan A. PMID: 30799288.

View in: PubMed Mentions: 81 Fields:
Cel Cell Biology Met Metabolism
Translation:Humans Animals Cells
Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells. Nat Cell Biol. 2019 02; 21(2):263-274. 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. PMID: 30710150; PMCID: PMC6746427.

View in: PubMed Mentions: 134 Fields:
Cel Cell Biology
Translation:Humans Animals Cells
Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally. Diabetes. 2019 02; 68(2):337-348. Cyphert HA, Walker EM, Hang Y, Dhawan S, Haliyur R, Bonatakis L, Avrahami D, Brissova M, Kaestner KH, Bhushan A, Powers AC, Stein R. PMID: 30425060; PMCID: PMC6341297.

View in: PubMed Mentions: 17 Fields:
End Endocrinology
Translation:Humans Animals Cells
Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. Cell Cycle. 2017; 16(22):2183-2191. Tschen SI, Zeng C, Field L, Dhawan S, Bhushan A, Georgia S. PMID: 28763258; PMCID: PMC5736344.

View in: PubMed Mentions: 4 Fields:
Cel Cell Biology
Translation:Animals Cells
β Cells led astray by transcription factors and the company they keep. J Clin Invest. 2017 01 03; 127(1):94-97. Thompson P, Bhushan A. PMID: 27941244; PMCID: PMC5199689.

View in: PubMed Mentions: 4 Fields:
Med Medicine (General)
Translation:Humans Animals Cells
Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication. Diabetes. 2016 05; 65(5):1208-18. Dhawan S, Dirice E, Kulkarni RN, Bhushan A. PMID: 26936960; PMCID: PMC4839200.

View in: PubMed Mentions: 51 Fields:
End Endocrinology
Translation:Humans Animals Cells
DNA methylation directs functional maturation of pancreatic β cells. J Clin Invest. 2015 Jul 01; 125(7):2851-60. Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A. PMID: 26098213; PMCID: PMC4563682.

View in: PubMed Mentions: 76 Fields:
Med Medicine (General)
Translation:Humans Animals Cells
Human β-cell proliferation and intracellular signaling: part 3. Diabetes. 2015 Jun; 64(6):1872-85. Stewart AF, Hussain MA, García-Ocaña A, Vasavada RC, Bhushan A, Bernal-Mizrachi E, Kulkarni RN. PMID: 25999530; PMCID: PMC4439562.

View in: PubMed Mentions: 72 Fields:
End Endocrinology
Translation:Humans Animals Cells
Combined modulation of polycomb and trithorax genes rejuvenates β cell replication. J Clin Invest. 2013 Nov; 123(11):4849-58. Zhou JX, Dhawan S, Fu H, Snyder E, Bottino R, Kundu S, Kim SK, Bhushan A. PMID: 24216481; PMCID: PMC3809789.

View in: PubMed Mentions: 33 Fields:
Med Medicine (General)
Translation:Humans Animals Cells
The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation. EMBO J. 2013 May 15; 32(10):1393-408. Kartikasari AE, Zhou JX, Kanji MS, Chan DN, Sinha A, Grapin-Botton A, Magnuson MA, Lowry WE, Bhushan A. PMID: 23584530; PMCID: PMC3655467.

View in: PubMed Mentions: 48 Fields:
Bio Biotechnology Mol Molecular Biology
Translation:Humans Animals Cells
DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis. Genes Dev. 2013 Feb 15; 27(4):372-7. Georgia S, Kanji M, Bhushan A. PMID: 23431054; PMCID: PMC3589554.

View in: PubMed Mentions: 39 Fields:
Mol Molecular Biology
Translation:Animals Cells
Dicer1 is required to repress neuronal fate during endocrine cell maturation. Diabetes. 2013 May; 62(5):1602-11. Kanji MS, Martin MG, Bhushan A. PMID: 23382448; PMCID: PMC3636616.

View in: PubMed Mentions: 15 Fields:
End Endocrinology
Translation:Animals Cells
Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming. Genes Dev. 2011 Nov 01; 25(21):2291-305. Papizan JB, Singer RA, Tschen SI, Dhawan S, Friel JM, Hipkens SB, Magnuson MA, Bhushan A, Sussel L. PMID: 22056672; PMCID: PMC3219233.

View in: PubMed Mentions: 99 Fields:
Mol Molecular Biology
Translation:Animals Cells
Skp2 is required for incretin hormone-mediated β-cell proliferation. Mol Endocrinol. 2011 Dec; 25(12):2134-43. Tschen SI, Georgia S, Dhawan S, Bhushan A. PMID: 21980072; PMCID: PMC3231831.

View in: PubMed Mentions: 18 Fields:
End Endocrinology Mol Molecular Biology
Translation:Humans Animals Cells
Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell. 2011 Apr 19; 20(4):419-29. Dhawan S, Georgia S, Tschen SI, Fan G, Bhushan A. PMID: 21497756; PMCID: PMC3086024.

View in: PubMed Mentions: 127 Fields:
Cel Cell Biology Emb Embryology
Translation:Animals Cells
Pregnancy hormones boost beta cells via serotonin. Nat Med. 2010 Jul; 16(7):756-7. Georgia S, Bhushan A. PMID: 20613752.

View in: PubMed Mentions: 5 Fields:
Med Medicine (General)Mol Molecular Biology
Translation:Animals Cells
Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats. Am J Physiol Endocrinol Metab. 2010 Nov; 299(5):E713-20. Matveyenko AV, Georgia S, Bhushan A, Butler PC. PMID: 20587750; PMCID: PMC3774125.

View in: PubMed Mentions: 26 Fields:
End Endocrinology Met Metabolism Phy Physiology
Translation:Humans Animals Cells
Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents. Diabetes. 2010 Apr; 59(4):987-96. Georgia S, Hinault C, Kawamori D, Hu J, Meyer J, Kanji M, Bhushan A, Kulkarni RN. PMID: 20103709; PMCID: PMC2844846.

View in: PubMed Mentions: 39 Fields:
End Endocrinology
Translation:Animals Cells
Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation. Genes Dev. 2009 Apr 15; 23(8):906-11. Dhawan S, Tschen SI, Bhushan A. PMID: 19390085; PMCID: PMC2675870.

View in: PubMed Mentions: 132 Fields:
Mol Molecular Biology
Translation:Animals Cells
Age-dependent decline in beta-cell proliferation restricts the capacity of beta-cell regeneration in mice. Diabetes. 2009 Jun; 58(6):1312-20. Tschen SI, Dhawan S, Gurlo T, Bhushan A. PMID: 19228811; PMCID: PMC2682690.

View in: PubMed Mentions: 175 Fields:
End Endocrinology
Translation:Animals Cells
Deletion of the mitochondrial flavoprotein apoptosis inducing factor (AIF) induces beta-cell apoptosis and impairs beta-cell mass. PLoS One. 2009; 4(2):e4394. Schulthess FT, Katz S, Ardestani A, Kawahira H, Georgia S, Bosco D, Bhushan A, Maedler K. PMID: 19197367; PMCID: PMC2632884.

View in: PubMed Mentions: 10 Fields:
Med Medicine (General)Sci Science
Translation:Humans Animals Cells
Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes. 2008 Jun; 57(6):1584-94. Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, Rizza RA, Butler PC. PMID: 18334605; PMCID: PMC3697779.

View in: PubMed Mentions: 349 Fields:
End Endocrinology
Translation:Humans Cells
Formation and regeneration of the endocrine pancreas. Curr Opin Cell Biol. 2007 Dec; 19(6):634-45. Dhawan S, Georgia S, Bhushan A. PMID: 18061427; PMCID: PMC2695413.

View in: PubMed Mentions: 30 Fields:
Cel Cell Biology
Translation:Humans Animals
The replication of beta cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab. 2007 Nov; 3(11):758-68. Butler PC, Meier JJ, Butler AE, Bhushan A. PMID: 17955017.

View in: PubMed Mentions: 128 Fields:
End Endocrinology Met Metabolism
Translation:Humans Animals Cells
Essential role of Skp2-mediated p27 degradation in growth and adaptive expansion of pancreatic beta cells. J Clin Invest. 2007 Oct; 117(10):2869-76. Zhong L, Georgia S, Tschen SI, Nakayama K, Nakayama K, Bhushan A. PMID: 17823659; PMCID: PMC1964513.

View in: PubMed Mentions: 56 Fields:
Med Medicine (General)
Translation:Animals Cells
Hematopoietic stem cells derived from adult donors are not a source of pancreatic beta-cells in adult nondiabetic humans. Diabetes. 2007 Jul; 56(7):1810-6. Butler AE, Huang A, Rao PN, Bhushan A, Hogan WJ, Rizza RA, Butler PC. PMID: 17456852.

View in: PubMed Mentions: 15 Fields:
End Endocrinology
Translation:Humans Cells
p27 Regulates the transition of beta-cells from quiescence to proliferation. Diabetes. 2006 Nov; 55(11):2950-6. Georgia S, Bhushan A. PMID: 17065330.

View in: PubMed Mentions: 55 Fields:
End Endocrinology
Translation:Animals Cells
p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Dev Biol. 2006 Oct 01; 298(1):22-31. Georgia S, Soliz R, Li M, Zhang P, Bhushan A. PMID: 16899237.

View in: PubMed Mentions: 71 Fields:
Bio Biology Emb Embryology
Translation:Animals Cells
The potential for stem cell therapy in diabetes. Pediatr Res. 2006 Apr; 59(4 Pt 2):65R-73R. Meier JJ, Bhushan A, Butler PC. PMID: 16549551.

View in: PubMed Mentions: 20 Fields:
Ped Pediatrics
Translation:Humans
Formation of pancreatic duct epithelium from bone marrow during neonatal development. Stem Cells. 2006 Feb; 24(2):307-14. Wang X, Ge S, Gonzalez I, McNamara G, Rountree CB, Xi KK, Huang G, Bhushan A, Crooks GM. PMID: 16510429.

View in: PubMed Mentions: 11 Fields:
Cel Cell Biology Emb Embryology
Translation:Animals Cells
Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest. 2004 Oct; 114(7):963-8. Georgia S, Bhushan A. PMID: 15467835; PMCID: PMC518666.

View in: PubMed Mentions: 242 Fields:
Med Medicine (General)
Translation:Animals
Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development. 2001 Dec; 128(24):5109-17. Bhushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R. PMID: 11748146.

View in: PubMed Mentions: 178 Fields:
Bio Biology Emb Embryology
Translation:Animals Cells
Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos. Dev Biol. 1998 Aug 15; 200(2):260-8. Bhushan A, Chen Y, Vale W. PMID: 9705232.

View in: PubMed Mentions: 10 Fields:
Bio Biology Emb Embryology
Translation:Animals Cells
Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase. Proc Natl Acad Sci U S A. 1997 Nov 25; 94(24):12938-43. Chen Y, Bhushan A, Vale W. PMID: 9371779; PMCID: PMC24242.

View in: PubMed Mentions: 29 Fields:
Sci Science
Translation:Animals Cells
The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm. Mol Cell Biol. 1994 Jun; 14(6):4280-5. Bhushan A, Lin HY, Lodish HF, Kintner CR. PMID: 8196664; PMCID: PMC358794.

View in: PubMed Mentions: 7 Fields:
Cel Cell Biology Mol Molecular Biology
Translation:Animals Cells