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Research

Gut communication in health and disease

The Andres Lab specializes in cellular physiology of health and disease within the gastrointestinal tract, with a particular interest in mechanisms that modulate intestinal barrier function in healthy and disease states. Our work is centered on mechanisms of barrier breakdown in inflammation and cancer, as well as methods of barrier repair using nutrient-based therapeutics.

    Human milk extracellular vesicles (EVs) and intestinal maturation 

    This work uses human patient samples and ex vivo patient-derived enteroids to define the effects of human digestion on human milk EVs and how these EVs in turn impact intestinal barrier function and cellular maturation.

     

    Two adjacent intestinal crypts, which house the intestinal stem cells that are responsible for maintaining and regenerating the intestinal epithelium.

    Neonatal human enteroid with the apical cell surface on the outside of the structure. Apical surface is labeled in green using phalloidin.

    This image shows intestinal crypts and villi (cell nuclei shown in blue). The red staining marks enteroendocrine cells, a subset of intestinal epithelial cells responsible for hormone secretion.

    Role of Imp1 in intercellular communication, barrier function, and necrotizing enterocolitis

    This project uses genetic mouse models and 3D patient-derived enteroids to define the role of the RNA binding protein insulin-like growth factor 2 mRNA binding protein 1 (Igf2bp1/Imp1) in the neonatal inflammatory disease (necrotizing enterocolitis).
    An electron micrograph of a cell with a large multivesicular body (arrow) containing many tiny exosomes (individual packages of biomolecular information).
    Green fluorescence staining of the brush border enzyme sucrase isomaltase. Sucrase isomaltase is highly expressed by the differentiated (mature) cells of the intestine. These cells line the finger-like structures shown (villi) which increase the absorptive and secretory surface area within the intestinal epithelium.
    Hematoxylin (blue, DNA) and eosin (pink, protein) stained image of a colon cancer metastasis in a mouse liver.

    Post-transcriptional regulation in the GI tract

    We demonstrated that the RNA binding protein IMP1 enters EVs secreted from colorectal cancer cells with high levels of IMP1 expression. This phenomenon appears to be unique to cancer cells, as IMP1 did not enter EVs secreted from non-transformed colon. Collectively this suggests that IMP1 has biomarker potential.
    Stay up to date on all our research!
    • IMP1 3′ UTR shortening enhances metastatic burden in colorectal cancer.
      Andres SF, Williams KN, Plesset JB, Headd JJ, Mizuno R, Chatterji P, Lento AA, Klein-Szanto AJ, Mick R, Hamilton KE, Rustgi AK.
      Carcinogenesis. 2019 Jun 10;40(4):569-579. doi: 10.1093/carcin/bgy153.
      PMID: 30407516
    • The Molecular Basis of Metastatic Colorectal Cancer.
      Andres SF, Williams KN, Rustgi AK.
      Curr Colorectal Cancer Rep. 2018 Apr;14(2):69-79. doi: 10.1007/s11888-018-0403-z. Epub 2018 Mar 1.
      PMID: 30237756
    • The LIN28B-IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine.
      Chatterji P, Hamilton KE, Liang S, Andres SF, Wijeratne HRS, Mizuno R, Simon LA, Hicks PD, Foley SW, Pitarresi JR, Klein-Szanto AJ, Mah AT, Van Landeghem L, Gregory BD, Lengner CJ, Madison BB, Shah P, Rustgi AK.
      Genes Dev. 2018 Aug 1;32(15-16):1020-1034. doi: 10.1101/gad.314369.118.
      PMID: 30068703
    • Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells.
      Moorefield EC, Andres SF, Blue RE, Van Landeghem L, Mah AT, Santoro MA, Ding S. Aging (Albany NY). 2017 Aug 29;9(8):1898-1915. doi: 10.18632/aging.101279.
      PMID: 28854151
    • Obesity and intestinal epithelial deletion of the insulin receptor, but not the IGF 1 receptor, affect radiation-induced apoptosis in colon.
      Santoro MA, Blue RE, Andres SF, Mah AT, Van Landeghem L, Lund PK.
      Am J Physiol Gastrointest Liver Physiol. 2015 Oct 1;309(7):G578-89. doi: 10.1152/ajpgi.00189.2015. Epub 2015 Aug 6.
      PMID: 26251471
    • Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon.
      Hamilton KE, Chatterji P, Lundsmith ET, Andres SF, Giroux V, Hicks PD, Noubissi FK, Spiegelman VS, Rustgi AK.
      Mol Cancer Res. 2015 Nov;13(11):1478-86. doi: 10.1158/1541-7786.MCR-15-0224. Epub 2015 Jul 20.
      PMID: 26194191
    • Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs. Andres SF, Santoro MA, Mah AT, Keku JA, Bortvedt AE, Blue RE, Lund PK.
      Am J Physiol Gastrointest Liver Physiol. 2015 Jan 15;308(2):G100-11. doi: 10.1152/ajpgi.00287.2014. Epub 2014 Nov 13.
      PMID: 25394660
    • Reduced insulin-like growth factor I receptor and altered insulin receptor isoform mRNAs in normal mucosa predict colorectal adenoma risk.
      Santoro MA, Andres SF, Galanko JA, Sandler RS, Keku TO, Lund PK.
      Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2093-100. doi: 10.1158/1055-9965.EPI-14-0177. Epub 2014 Jul 13.
      PMID: 25017244
    • Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation.
      Andres SF, Simmons JG, Mah AT, Santoro MA, Van Landeghem L, Lund PK.
      J Cell Sci. 2013 Dec 15;126(Pt 24):5645-56. doi: 10.1242/jcs.132985. Epub 2013 Oct 14.
      PMID: 24127567
    • Conference report: placental growth and function.
      Challis JR, Andres SF, Catz CS, Fisher SJ, Hay WW Jr, Hunt JS, Illsley NP, Thornburg KL.
      Placenta. 1995 Jul;16(5):471-5. Review. No abstract available.
      PMID: 7479619
    • Immunochemistry of sperm-whale myoglobin–XXI. Conformation and immunochemistry of derivatives modified at certain histidine residues.
      Atassi MZ, Litowich MT, Andres SF.
      Immunochemistry. 1975 Sep;12(9):727-33. No abstract available.
      PMID: 1193678
    • Clinical determination of methemalbumin.
      Andres SF, Kregoski TJ, Frey CF, Joseph RR, McCann DS.
      Clin Chem. 1975 Sep;21(10):1506-10.
      PMID: 1157322
    • Immunochemistry of sperm-whale myoglobin. Conformation and immunochemistry of derivatives prepared by reaction with diazonium-1H-tetrazole. Evaluation of the specificity of the reagent.
      Andres SF, Atassi MZ. Biochemistry. 1973 Feb 27;12(5):942-7. No abstract available.
      PMID: 4631371
    • Conformational studies on modified proteins and peptides. Artificial myoglobins prepared with modified and metalloporphyrins.
      Andres SF, Atassi MZ.
      Biochemistry. 1970 May 26;9(11):2268-75. No abstract available.
      PMID: 5424201
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