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Anil Bhushan, PhD

Title(s)Professor, Diabetes Center
SchoolSchool of Medicine
Address513 Parnassus Ave, HSW
San Francisco CA 94143
Phone415-502-3295
EmailAnil.Bhushan@ucsf.edu
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    Collapse Biography 
    Collapse Education and Training
    Salk Institute, La Jolla, CAPostdoctoral 1999Development Biology
    UCDavis, Davis CAPhD1992Biochemistry and Biophysics
    INSERM, Paris, France2001Diabetes

    Collapse Overview 
    Collapse 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.

    Collapse Research 
    Collapse Research Activities and Funding
    Modulating the senescence secretome to block progression of T1D
    NIH/NIDDK R01DK118099Jan 1, 2020 - Dec 31, 2023
    Role: Principal Investigator
    Targeting Senescence for Biomarkers and Therapeutics
    NIH/NIDDK R01DK121794Jul 1, 2019 - Jun 30, 2022
    Role: Principal Investigator
    Mechanisms of beta cell maturation
    NIH/NIDDK R01DK108666Sep 30, 2015 - Jul 31, 2019
    Role: Co-Principal Investigator
    Polycomb genes regulation of beta cell regeneration
    NIH/NIDDK R01DK080996Feb 1, 2010 - Oct 31, 2010
    Role: Principal Investigator
    Cell Cycle Control Of Beta Cell Mass
    NIH/NIDDK R01DK068763Jul 5, 2004 - Sep 24, 2010
    Role: Principal Investigator
    SPECIFICITY OF ACTIVIN SIGNALING THROUGH TYPE I RECEPTOR
    NIH/NICHD F32HD007969Mar 16, 1996
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse 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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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. 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.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    2. mTORC1 to AMPK switching underlies ß-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.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    3. The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet ß-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.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    4. Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß 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:    Fields:    
    5. 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: 16     Fields:    Translation:HumansAnimalsCells
    6. Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß 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.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimalsCells
    7. Examining How the MAFB Transcription Factor Affects Islet ß-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.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    8. Cyclin D2 is sufficient to drive ß 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.
      View in: PubMed   Mentions:
    9. ß 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.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    10. Inhibition of TGF-ß Signaling Promotes Human Pancreatic ß-Cell Replication. Diabetes. 2016 05; 65(5):1208-18. Dhawan S, Dirice E, Kulkarni RN, Bhushan A. PMID: 26936960.
      View in: PubMed   Mentions: 18     Fields:    Translation:HumansAnimalsCells
    11. DNA methylation directs functional maturation of pancreatic ß 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.
      View in: PubMed   Mentions: 40     Fields:    Translation:HumansAnimalsCells
    12. Human ß-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.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    13. Combined modulation of polycomb and trithorax genes rejuvenates ß 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.
      View in: PubMed   Mentions: 28     Fields:    Translation:HumansAnimalsCells
    14. 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.
      View in: PubMed   Mentions: 37     Fields:    Translation:HumansAnimalsCells
    15. 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.
      View in: PubMed   Mentions: 24     Fields:    Translation:AnimalsCells
    16. 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.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    17. Nkx2.2 repressor complex regulates islet ß-cell specification and prevents ß-to-a-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.
      View in: PubMed   Mentions: 71     Fields:    Translation:AnimalsCells
    18. Skp2 is required for incretin hormone-mediated ß-cell proliferation. Mol Endocrinol. 2011 Dec; 25(12):2134-43. Tschen SI, Georgia S, Dhawan S, Bhushan A. PMID: 21980072.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansAnimalsCells
    19. Pancreatic ß 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.
      View in: PubMed   Mentions: 94     Fields:    Translation:AnimalsCells
    20. 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:    Translation:AnimalsCells
    21. 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.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    22. 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.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    23. 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.
      View in: PubMed   Mentions: 113     Fields:    Translation:AnimalsCells
    24. 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.
      View in: PubMed   Mentions: 136     Fields:    Translation:AnimalsCells
    25. 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.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansAnimalsCells
    26. 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.
      View in: PubMed   Mentions: 273     Fields:    Translation:HumansCells
    27. 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.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimals
    28. 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: 109     Fields:    Translation:HumansAnimalsCells
    29. 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.
      View in: PubMed   Mentions: 53     Fields:    Translation:AnimalsCells
    30. 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: 13     Fields:    Translation:HumansCells
    31. 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: 49     Fields:    Translation:AnimalsCells
    32. 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: 62     Fields:    Translation:AnimalsCells
    33. 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: 17     Fields:    Translation:Humans
    34. 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:    Translation:AnimalsCells
    35. 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.
      View in: PubMed   Mentions: 209     Fields:    Translation:Animals
    36. 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: 152     Fields:    Translation:AnimalsCells
    37. 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:    Translation:AnimalsCells
    38. 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.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    39. 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.
      View in: PubMed   Mentions: 7     Fields:    Translation:AnimalsCells
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