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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.


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.

One or more keywords matched the following items that are connected to Ip, Yicktung
Item TypeName
Academic Article The mesoderm determinant snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis.
Academic Article Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo.
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Academic Article Hemolymph-dependent and -independent responses in Drosophila immune tissue.
Academic Article Regulators of the Toll and Imd pathways in the Drosophila innate immune response.
Academic Article Tissue damage-induced intestinal stem cell division in Drosophila.
Academic Article Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila.
Academic Article Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.
Academic Article Worniu, a Snail family zinc-finger protein, is required for brain development in Drosophila.
Academic Article Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo.
Academic Article Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster.
Academic Article Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells.
Academic Article Smad inhibition by the Ste20 kinase Misshapen.
Concept Drosophila melanogaster
Academic Article Gudu, an Armadillo repeat-containing protein, is required for spermatogenesis in Drosophila.
Academic Article Regulation of Toll signaling and inflammation by ?-arrestin and the SUMO protease Ulp1.
Academic Article The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo.
Academic Article Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo.
Academic Article Dif, a dorsal-related gene that mediates an immune response in Drosophila.
Academic Article Characterization of a MEN1 ortholog from Drosophila melanogaster.
Academic Article A Drosophila p38 orthologue is required for environmental stress responses.
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Academic Article Functional analysis of Toll-related genes in Drosophila.
Academic Article Retromer promotes immune quiescence by suppressing Sp?tzle-Toll pathway in Drosophila.
Academic Article The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila.
Academic Article More Frequent than Desired: Midgut Stem Cell Somatic Mutations.
Academic Article How Toll Met Hippo.
Academic Article Ingestion of Food Particles Regulates the Mechanosensing Misshapen-Yorkie Pathway in Drosophila Intestinal Growth.
Academic Article Toll family members bind multiple Sp?tzle proteins and activate antimicrobial peptide gene expression in Drosophila.
Academic Article Oncogenic Pathways and Loss of the Rab11 GTPase Synergize To Alter Metabolism in Drosophila.
Academic Article The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila.
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  • Drosophila melanogaster