A5020557933- Invertebrate Immune Response Mechanisms
- Developmental Biology and Gene Regulation
- Neurobiology and Insect Physiology Research
- Hippo pathway signaling and YAP/TAZ
- Insect symbiosis and bacterial influences
- Antimicrobial Peptides and Activities
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- NF-κB Signaling Pathways
- Epigenetics and DNA Methylation
- TGF-β signaling in diseases
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Marine Biology and Environmental Chemistry
- Immune Response and Inflammation
- Animal Genetics and Reproduction
- Insect Utilization and Effects
- Cytokine Signaling Pathways and Interactions
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Heat shock proteins research
- RNA Research and Splicing
- Melanoma and MAPK Pathways
- Kruppel-like factors research
- Ubiquitin and proteasome pathways
University of Massachusetts Chan Medical School
2016-2025
Massachusetts General Hospital
2024
Harvard University
2024
Shanghai Chest Hospital
2024
Shanghai Jiao Tong University
2024
Institute of Molecular Medicine
2007-2011
Institute of Cell Biology
2007
University of Massachusetts Boston
2005
Institute of Molecular and Cell Biology
2000
University of Massachusetts Amherst
1995-1998
The Drosophila MAP kinase DJNK is a homolog of the mammalian c-Jun amino-terminal (JNK). Mutations in gene correspond to complementation group basket. phosphorylated and activated by HEP. Substrates include transcription factor DJun. participates multiple physiological processes. Exposure endotoxic lipopolysaccharide initiates an insect immune response leads activation. In addition, embryos lacking are defective dorsal closure, process which lateral epithelial cells migrate over embryo join...
A gradient of the maternal morphogen dorsal (dl) initiates differentiation various tissues along dorsal-ventral axis early Drosophila embryos. dl is a sequence-specific DNA-binding protein that related to mammalian regulatory factor NF-kappa B. Previous studies suggest can function as transcriptional repressor. To determine how functions an activator we have examined promoter mesoderm determinant gene twist (twi). Genetic peak levels in ventral regions embryos initiate twi expression. Using...
The inducible expression of antimicrobial peptide genes in Drosophila melanogaster is regulated by the conserved Toll and peptidoglycan recognition protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways. It has been proposed that two pathways have independent functions mediate specificity innate immune responses towards different microorganisms. Scattered evidence also suggests some target can be activated both IMD, albeit to extents. This dual activation mediated stimulation or...
Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis and replenishing lost response to damage. Here we demonstrate that Hippo (Hpo) signaling pathway, an evolutionarily conserved pathway implicated organ size control tumorigenesis, plays role regulating ISC proliferation. Loss of Hpo either precursor or epithelial stimulates We provide evidence loss increases production cytokines Upd family multiple EGFR ligands activate JAK-STAT...
Abstract Targeting TEAD autopalmitoylation has been proposed as a therapeutic approach for YAP-dependent cancers. Here we show that palmitoylation inhibitor MGH-CP1 and analogues block cancer cell “stemness”, organ overgrowth tumor initiation in vitro vivo. sensitivity correlates significantly with YAP-dependency large panel of lines. However, inhibition or YAP/TAZ knockdown leads to transient cycle progression without inducing death, undermining their potential utilities. We further reveal...
rhomboid (rho) encodes a putative transmembrane receptor that is required for the differentiation of ventral epidermis. It initially expressed before completion cellularization in lateral stripes within presumptive neuroectoderm. Here, we present evidence maternal morphogen dorsal (dl) acts concert with basic helix-loop-helix (b-HLH) proteins, possibly including twist (twi), to activate rho both and regions. Expression blocked regions (the mesoderm) by snail (sna), which also direct target...
The first step in the differentiation of Drosophila mesoderm is activation two regulatory genes, twist (twi) and snail (sna), ventral regions early embryos. sna a transcriptional repressor that uniformly expressed throughout presumptive mesoderm. Its sharp lateral limits help to establish boundary between neuroectoderm. Genetic studies suggest target dorsal (dl) morphogen, this interaction provides model for determining how morphogen gradient establishes sharp, on/off threshold response. We...
The induction of immunity genes in Drosophila has been proposed to be dependent on Dorsal, Dif, and Relish, the NF-kappaB-related factors. Here we provide genetic evidence that Dif is required for only a subset antimicrobial peptide genes. results show presence without Dorsal sufficient mediate drosomycin defensin. We also demonstrate downstream component Toll signaling pathway activating expression. These reveal individual members NF-kappaB family have distinct roles development.
A gradient of the maternal morphogen dorsal establishes asymmetric patterns gene expression along dorsal-ventral axis early embryos and activates regulatory genes twist snail , which are responsible for differentiation ventral mesoderm. Expression is restricted to presumptive mesoderm, sharp lateral limits this help define mesoderm-neuroectoderm boundary by repressing that neuroectoderm. The encodes a zinc finger protein, neuroectodermal normally ventral-lateral regions expressed throughout...
Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components.Proinflammatory cytokines bacterial lipopolysaccharide stimulate immunity activating transcription factors such as NF-B AP-1.One of responses evoked these stimuli initiation a kinase cascade leads to phosphorylation p38 mitogen-activated protein (MAP) on Thr Tyr within motif Thr-Gly-Tyr, which located subdomain VIII.We have investigated possible involvement MAP...
Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from surrounding niche including enterocytes and visceral muscle. The role of other major cell type, secretory enteroendocrine cells, regulating intestinal remains unclear. We show here that newly eclosed scute loss-of-function mutant flies completely devoid cells. These cell-less have normal ingestion fecundity but shorter lifespan. Moreover, these flies, diet-stimulated depends on insulin-like...
The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. canonical receptor (Toll-1) is activated by cytokine Spätzle (Spz-1), but encodes eight other genes and five Spz whose interactions with one another associated functions are less well-understood. Here, we conducted vitro assays S2 cell line Toll/interleukin-1 (TIR) homology domains each family member to determine whether they can...
Phosphorylation of the SSXS motif Smads is critical in activating transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) pathways. However, phosphatase(s) involved dephosphorylating hence inactivating remained elusive. Through RNA interference (RNAi)-based screening serine/threonine phosphatases Drosophila S2 cells, we identified pyruvate dehydrogenase phosphatase (PDP) to be required for dephosphorylation Mothers against Decapentaplegic (MAD), a Smad. Biochemical genetic...
The Toll family of receptors is required for innate immune response to pathogen-associated molecules, but the mechanism signaling not entirely clear. In Drosophila prototypic regulates both embryonic development and adult response. We demonstrate here that host protein Spätzle can function as a ligand because forms complex with in transgenic fly extracts stimulates expression Toll-dependent immunity gene, drosomycin , flies. also show constitutively active mutants form multimers contain...
Stem cell-mediated tissue repair is a promising approach for many diseases. Mammalian intestine an actively regenerating such that epithelial cells are constantly shedding and underlying precursor replenishing the loss of cells. An imbalance these processes will lead to intestinal diseases including inflammation cancer. stem (ISCs) located in bases crypts but at least two groups have been cited as Moreover, transit amplifying zone can also proliferate. The involvement multiple cell types...
The innate immune response in Drosophila involves the inducible expression of antimicrobial peptide genes mediated by Toll and IMD signaling pathways. Dorsal DIF act downstream Toll, whereas Relish acts to regulate target gene expression. Dorsal, DIF, are NF-κB-related transcription factors function as obligate dimers, but it is not clear how various dimer combinations contribute response. We systematically examined dimerization tendency these proteins through use transgenic assays. results...