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Yicktung T Ip PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentProgram in Molecular Medicine
AddressUniversity of Massachusetts Medical School
373 Plantation Street, Two Biotech, Suite 109
Worcester MA 01605
Phone508-856-5136
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - School of Medicine
    DepartmentProgram in Molecular Medicine

    InstitutionUMMS - School of Medicine
    DepartmentRadiology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCell Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program


    Collapse Biography 
    Collapse education and training
    National Defense University, Taoyuan City, , TaiwanBSPharmacy
    University of Iowa, Iowa City, IA, United StatesPHDBiochemistry

    Collapse Overview 
    Collapse overview

    Academic background

    Tony Ip received his BS from the National Defense Medical Center, Taipei, ROC in 1984 and his PhD from the University of Iowa in 1989. He was a Hoffmann-LaRoche Fellow of the Life Sciences Research Foundation from 1991-1994 at the University of California at San Diego. In 1994, he joined the University of Massachusetts Medical Center as assistant professor in the Program in Molecular Medicine. He was a recipient of a Scholar Award of the Leukemia Society of America in 1996-2001.

    Intestinal stem cells and tissue regeneration in Drosophila

    Dr. Tony Ip

    Humans and fruit flies do not look alike, yet many physiological processes in these two organisms share homologous molecules.We use Drosophila melanogaster, the common fruit fly, as a model organism to study the mechanisms by which intestinal stem cells respond to injury and initiate tissue repair. Around 1% of the US population experience inflammatory diseases of the intestine. Prolonged inflammation and tissue injury has also been proposed to potentiate gastrointestinal (GI) cancer. To understand how cells in the GI tract interact with wide varieties of microbes and pathogenic substances is important for developing therapeutic strategies that alleviate intestinal diseases. The human gastrointestinal tract is the major nutrient absorption organ that also has immune and endocrine function. It is also a major site for interaction with commensal bacteria and pathogenic substances. However, the human gastrointestinal tract is a relatively under-explored organ due to the complexity of the organ and the difficulty in experimental manipulation. Stem cell-mediated tissue repair is a promising approach for intestinal diseases. A major problem in intestinal stem cell research is that specific markers that can unambiguously identify these stem cells remain rare and the functions of these markers remain difficulty to study.

    My laboratory focuses on understanding how Drosophila intestinal stem cells mediate repair after tissue damage. Drosophila has emerged as a powerful tool for analyzing the function of human disease genes, either as fly homologues or by expressing in transgenic flies the mutated forms of human genes. Drosophila midgut is only 1 cm long and has a relatively simple cellular organization. Midgut intestinal stem cells have recently been identified that function to replenish the different cell types. We have demonstrated that these Drosophila intestinal stem cells can increase their division rate in response to tissue damage. Using this newly established system, we also show that intestinal stem cell division requires insulin signaling, a mechanism not yet shown in mammals thus suggesting that new information can be obtained from this system. To analyze how insulin and other regulatory pathways control intestinal stem cell division is our ongoing research direction. We have identified by transgenic expression assays and RNAi-based genetic screens a number of genes that are essential for damage-induced intestinal stem cell division. By studying the mechanisms of tissue damage-induced stem division in the genetically amenable Drosophila system, important insights will hopefully be obtained that can help to understand human stem cell-mediated tissue repair, intestinal inflammatory diseases and cancer progression.

    Figure1

    Figure Legend

    Cellular organization in adult Drosophila midgut. Left panel is DAPI staining for DNA in midgut. Right panel is a confocal image of midgut cross section. Phalloidin stains smooth muscle cells at the basal side and brush border of enterocytes at the lumenal side. Intestinal stem cells are some of the small cells located near the basal side. In adult Drosophila midgut, intestinal stem cell is the only cell type that divides and gives rise to all other cell types. We want to understand how the stem cell division is regulated, how the damaged epithelium is repaired, and how differentiation into various cell types is determined.




    Collapse Rotation Projects

    Rotation Projects

    Project #1: Mechanistic study of isolated mutants that show abnormal intestinal stem cell division phenotypes.

    Project #2:Perform transgenic RNAi-based genetic screen for genes required for intestinal stem cell response to tissue damage.



    Collapse Post Docs

    A postdoctoral position is available to study in this laboratory. Contact Dr. Ip for additional details.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Nie Y, Ip YT. How Toll Met Hippo. Dev Cell. 2016 Feb 8; 36(3):246-8. PMID: 26859349.
      View in: PubMed
    2. Li Q, Ip YT. More Frequent than Desired: Midgut Stem Cell Somatic Mutations. Cell Stem Cell. 2015 Dec 3; 17(6):639-40. PMID: 26637937.
      View in: PubMed
    3. Nie Y, Li Q, Amcheslavsky A, Duhart JC, Veraksa A, Stocker H, Raftery LA, Ip YT. Bunched and Madm Function Downstream of Tuberous Sclerosis Complex to Regulate the Growth of Intestinal Stem Cells in Drosophila. Stem Cell Rev. 2015 Dec; 11(6):813-25. PMID: 26323255.
      View in: PubMed
    4. Li S, Cho YS, Yue T, Ip YT, Jiang J. Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling. Cell Discov. 2015; 1:15038. PMID: 27462435.
      View in: PubMed
    5. Li Q, Li S, Mana-Capelli S, Roth Flach RJ, Danai LV, Amcheslavsky A, Nie Y, Kaneko S, Yao X, Chen X, Cotton JL, Mao J, McCollum D, Jiang J, Czech MP, Xu L, Ip YT. The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Dev Cell. 2014 Nov 10; 31(3):291-304. PMID: 25453828.
      View in: PubMed
    6. Amcheslavsky A, Song W, Li Q, Nie Y, Bragatto I, Ferrandon D, Perrimon N, Ip YT. Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila. Cell Rep. 2014 Oct 9; 9(1):32-9. PMID: 25263551.
      View in: PubMed
    7. Yu S, Nie Y, Knowles B, Sakamori R, Stypulkowski E, Patel C, Das S, Douard V, Ferraris RP, Bonder EM, Goldenring JR, Ip YT, Gao N. TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis. EMBO J. 2014 Sep 1; 33(17):1882-95. PMID: 25063677.
      View in: PubMed
    8. Amcheslavsky A, Nie Y, Li Q, He F, Tsuda L, Markstein M, Ip YT. Gene expression profiling identifies the zinc-finger protein Charlatan as a regulator of intestinal stem cells in Drosophila. Development. 2014 Jul; 141(13):2621-32. PMID: 24961799.
      View in: PubMed
    9. Zhou B, Yun EY, Ray L, You J, Ip YT, Lin X. Retromer promotes immune quiescence by suppressing Spätzle-Toll pathway in Drosophila. J Cell Physiol. 2014 Apr; 229(4):512-20. PMID: 24343480.
      View in: PubMed
    10. Anjum SG, Xu W, Nikkholgh N, Basu S, Nie Y, Thomas M, Satyamurti M, Budnik BA, Ip YT, Veraksa A. Regulation of Toll signaling and inflammation by ß-arrestin and the SUMO protease Ulp1. Genetics. 2013 Dec; 195(4):1307-17. PMID: 24077307.
      View in: PubMed
    11. Cheng W, Ip YT, Xu Z. Gudu, an Armadillo repeat-containing protein, is required for spermatogenesis in Drosophila. Gene. 2013 Dec 1; 531(2):294-300. PMID: 24055424.
      View in: PubMed
    12. Ren F, Shi Q, Chen Y, Jiang A, Ip YT, Jiang H, Jiang J. Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration. Cell Res. 2013 Sep; 23(9):1133-46. PMID: 23896988.
      View in: PubMed
    13. Nirala NK, Rahman M, Walls SM, Singh A, Zhu LJ, Bamba T, Fukusaki E, Srideshikan SM, Harris GL, Ip YT, Bodmer R, Acharya UR. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis. PLoS Genet. 2013 Jun; 9(6):e1003556. PMID: 23818862.
      View in: PubMed
    14. Amcheslavsky A, Ip YT. Be a good neighbor: organ-to-organ communication during the innate immune response. Cell Host Microbe. 2012 Apr 19; 11(4):323-4. PMID: 22520460.
      View in: PubMed
    15. Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L. Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5; 108(27):11127-32. PMID: 21690388.
      View in: PubMed
    16. Amcheslavsky A, Ito N, Jiang J, Ip YT. Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells. J Cell Biol. 2011 May 16; 193(4):695-710. PMID: 21555458.
      View in: PubMed
    17. Yagi Y, Nishida Y, Ip YT. Functional analysis of Toll-related genes in Drosophila. Dev Growth Differ. 2010 Dec; 52(9):771-83. PMID: 21158756.
      View in: PubMed
    18. Ren F, Wang B, Yue T, Yun EY, Ip YT, Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A. 2010 Dec 7; 107(49):21064-9. PMID: 21078993.
      View in: PubMed
    19. Chen S, Kaneko S, Ma X, Chen X, Ip YT, Xu L, Xie T. Lissencephaly-1 controls germline stem cell self-renewal through modulating bone morphogenetic protein signaling and niche adhesion. Proc Natl Acad Sci U S A. 2010 Nov 16; 107(46):19939-44. PMID: 21041636.
      View in: PubMed
    20. Tanji T, Yun EY, Ip YT. Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proc Natl Acad Sci U S A. 2010 Aug 17; 107(33):14715-20. PMID: 20679214.
      View in: PubMed
    21. Chatterjee M, Ip YT. Pathogenic stimulation of intestinal stem cell response in Drosophila. J Cell Physiol. 2009 Sep; 220(3):664-71. PMID: 19452446.
      View in: PubMed
    22. Amcheslavsky A, Jiang J, Ip YT. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell. 2009 Jan 9; 4(1):49-61. PMID: 19128792.
      View in: PubMed
    23. Xu L, Yao X, Chen X, Lu P, Zhang B, Ip YT. Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads. J Cell Biol. 2007 Sep 10; 178(6):981-94. PMID: 17785517.
      View in: PubMed
    24. Tanji T, Hu X, Weber AN, Ip YT. Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol. 2007 Jun; 27(12):4578-88. PMID: 17438142.
      View in: PubMed
    25. Chen HB, Shen J, Ip YT, Xu L. Identification of phosphatases for Smad in the BMP/DPP pathway. Genes Dev. 2006 Mar 15; 20(6):648-53. PMID: 16510868.
      View in: PubMed
    26. Yagi Y, Ip YT. Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila. EMBO Rep. 2005 Nov; 6(11):1088-94. PMID: 16200050.
      View in: PubMed
    27. Ip YT. Drosophila innate immunity goes viral. Nat Immunol. 2005 Sep; 6(9):863-4. PMID: 16116462.
      View in: PubMed
    28. Ganguly A, Jiang J, Ip YT. Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo. Development. 2005 Aug; 132(15):3419-29. PMID: 15987775.
      View in: PubMed
    29. Tanji T, Ip YT. Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol. 2005 Apr; 26(4):193-8. PMID: 15797509.
      View in: PubMed
    30. Craig CR, Fink JL, Yagi Y, Ip YT, Cagan RL. A Drosophila p38 orthologue is required for environmental stress responses. EMBO Rep. 2004 Nov; 5(11):1058-63. PMID: 15514678.
      View in: PubMed
    31. Ashraf SI, Ganguly A, Roote J, Ip YT. Worniu, a Snail family zinc-finger protein, is required for brain development in Drosophila. Dev Dyn. 2004 Oct; 231(2):379-86. PMID: 15366015.
      View in: PubMed
    32. Bettencourt R, Asha H, Dearolf C, Ip YT. Hemolymph-dependent and -independent responses in Drosophila immune tissue. J Cell Biochem. 2004 Jul 1; 92(4):849-63. PMID: 15211580.
      View in: PubMed
    33. Hu X, Yagi Y, Tanji T, Zhou S, Ip YT. Multimerization and interaction of Toll and Spätzle in Drosophila. Proc Natl Acad Sci U S A. 2004 Jun 22; 101(25):9369-74. PMID: 15197269.
      View in: PubMed
    34. Hemavathy K, Hu X, Ashraf SI, Small SJ, Ip YT. The repressor function of snail is required for Drosophila gastrulation and is not replaceable by Escargot or Worniu. Dev Biol. 2004 May 15; 269(2):411-20. PMID: 15110709.
      View in: PubMed
    35. Bettencourt R, Ip YT. Learning the codes of fly immunity. Mol Cell. 2004 Jan 16; 13(1):1-2. PMID: 14731387.
      View in: PubMed
    36. Bettencourt R, Tanji T, Yagi Y, Ip YT. Toll and Toll-9 in Drosophila innate immune response. J Endotoxin Res. 2004; 10(4):261-8. PMID: 15373972.
      View in: PubMed
    37. Ip YT, Gridley T. Cell movements during gastrulation: snail dependent and independent pathways. Curr Opin Genet Dev. 2002 Aug; 12(4):423-9. PMID: 12100887.
      View in: PubMed
    38. Lehmann M, Jiang C, Ip YT, Thummel CS. AP-1, but not NF-kappa B, is required for efficient steroid-triggered cell death in Drosophila. Cell Death Differ. 2002 May; 9(5):581-90. PMID: 11973616.
      View in: PubMed
    39. Ooi JY, Yagi Y, Hu X, Ip YT. The Drosophila Toll-9 activates a constitutive antimicrobial defense. EMBO Rep. 2002 Jan; 3(1):82-7. PMID: 11751574.
      View in: PubMed
    40. Ashraf SI, Ip YT. The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila. Development. 2001 Dec; 128(23):4757-67. PMID: 11731456.
      View in: PubMed
    41. Guru SC, Prasad NB, Shin EJ, Hemavathy K, Lu J, Ip YT, Agarwal SK, Marx SJ, Spiegel AM, Collins FS, Oliver B, Chandrasekharappa SC. Characterization of a MEN1 ortholog from Drosophila melanogaster. Gene. 2001 Jan 24; 263(1-2):31-8. PMID: 11223240.
      View in: PubMed
    42. Hemavathy K, Ashraf SI, Ip YT. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene. 2000 Oct 17; 257(1):1-12. PMID: 11054563.
      View in: PubMed
    43. Hemavathy K, Guru SC, Harris J, Chen JD, Ip YT. Human Slug is a repressor that localizes to sites of active transcription. Mol Cell Biol. 2000 Jul; 20(14):5087-95. PMID: 10866665.
      View in: PubMed
    44. Ashraf SI, Hu X, Roote J, Ip YT. The mesoderm determinant snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis. EMBO J. 1999 Nov 15; 18(22):6426-38. PMID: 10562554.
      View in: PubMed
    45. Han ZS, Ip YT. Interaction and specificity of Rel-related proteins in regulating Drosophila immunity gene expression. J Biol Chem. 1999 Jul 23; 274(30):21355-61. PMID: 10409696.
      View in: PubMed
    46. Meng X, Khanuja BS, Ip YT. Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB factor. Genes Dev. 1999 Apr 1; 13(7):792-7. PMID: 10197979.
      View in: PubMed
    47. Ashraf SI, Ip YT. Transcriptional control: repression by local chromatin modification. Curr Biol. 1998 Sep 24; 8(19):R683-6. PMID: 9768353.
      View in: PubMed
    48. Han ZS, Enslen H, Hu X, Meng X, Wu IH, Barrett T, Davis RJ, Ip YT. A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression. Mol Cell Biol. 1998 Jun; 18(6):3527-39. PMID: 9584193.
      View in: PubMed
    49. Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development. Curr Opin Cell Biol. 1998 Apr; 10(2):205-19. PMID: 9561845.
      View in: PubMed
    50. Hemavathy K, Meng X, Ip YT. Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo. Development. 1997 Oct; 124(19):3683-91. PMID: 9367424.
      View in: PubMed
    51. Ip YT, Hemavathy K. Drosophila development. Delimiting patterns by repression. Curr Biol. 1997 Apr 1; 7(4):R216-8. PMID: 9162494.
      View in: PubMed
    52. Sluss HK, Han Z, Barrett T, Goberdhan DC, Wilson C, Davis RJ, Ip YT. A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev. 1996 Nov 1; 10(21):2745-58. PMID: 8946915.
      View in: PubMed
    53. Petersen UM, Björklund G, Ip YT, Engström Y. The dorsal-related immunity factor, Dif, is a sequence-specific trans-activator of Drosophila Cecropin gene expression. EMBO J. 1995 Jul 3; 14(13):3146-58. PMID: 7621828.
      View in: PubMed
    54. Tatei K, Cai H, Ip YT, Levine M. Race: a Drosophila homologue of the angiotensin converting enzyme. Mech Dev. 1995 Jun; 51(2-3):157-68. PMID: 7547464.
      View in: PubMed
    55. Ip YT. Transcriptional regulation. Converting an activator into a repressor. Curr Biol. 1995 Jan 1; 5(1):1-3. PMID: 7697337.
      View in: PubMed
    56. Ip YT, Maggert K, Levine M. Uncoupling gastrulation and mesoderm differentiation in the Drosophila embryo. EMBO J. 1994 Dec 15; 13(24):5826-34. PMID: 7813421.
      View in: PubMed
    57. Ip YT, Levine M. Molecular genetics of Drosophila immunity. Curr Opin Genet Dev. 1994 Oct; 4(5):672-7. PMID: 7849506.
      View in: PubMed
    58. Ip YT, Levine M, Bier E. Neurogenic expression of snail is controlled by separable CNS and PNS promoter elements. Development. 1994 Jan; 120(1):199-207. PMID: 8119127.
      View in: PubMed
    59. Ip YT, Reach M, Engstrom Y, Kadalayil L, Cai H, González-Crespo S, Tatei K, Levine M. Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell. 1993 Nov 19; 75(4):753-63. PMID: 8242747.
      View in: PubMed
    60. Ip YT, Park RE, Kosman D, Bier E, Levine M. The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo. Genes Dev. 1992 Sep; 6(9):1728-39. PMID: 1325394.
      View in: PubMed
    61. Ip YT, Park RE, Kosman D, Yazdanbakhsh K, Levine M. dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev. 1992 Aug; 6(8):1518-30. PMID: 1644293.
      View in: PubMed
    62. Ip YT, Levine M, Small SJ. The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo. J Cell Sci Suppl. 1992; 16:33-8. PMID: 1297650.
      View in: PubMed
    63. Kosman D, Ip YT, Levine M, Arora K. Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. Science. 1991 Oct 4; 254(5028):118-22. PMID: 1925551.
      View in: PubMed
    64. Jiang J, Kosman D, Ip YT, Levine M. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Genes Dev. 1991 Oct; 5(10):1881-91. PMID: 1655572.
      View in: PubMed
    65. Ip YT, Kraut R, Levine M, Rushlow CA. The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell. 1991 Jan 25; 64(2):439-46. PMID: 1988156.
      View in: PubMed
    66. Ip YT, Poon D, Stone D, Granner DK, Chalkley R. Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1990 Jul; 10(7):3770-81. PMID: 2355922.
      View in: PubMed
    67. Ip YT, Fournier RE, Chalkley R. Extinction of phosphoenolpyruvate carboxykinase gene expression is associated with loss of a specific chromatin-binding protein from a far upstream domain. Mol Cell Biol. 1990 Jul; 10(7):3782-7. PMID: 2355923.
      View in: PubMed
    68. Ip YT, Granner DK, Chalkley R. Hormonal regulation of phosphoenolpyruvate carboxykinase gene expression is mediated through modulation of an already disrupted chromatin structure. Mol Cell Biol. 1989 Mar; 9(3):1289-97. PMID: 2657389.
      View in: PubMed
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