@article{sheahan_theriot_cortes_dekaney_2022, title={Prolonged oral antimicrobial administration prevents doxorubicin-induced loss of active intestinal stem cells}, volume={14}, ISSN={["1949-0984"]}, DOI={10.1080/19490976.2021.2018898}, abstractNote={ABSTRACT Acute intestinal mucositis is a common off-target effect of chemotherapy, leading to co-morbidities such as vomiting, diarrhea, sepsis, and death. We previously demonstrated that the presence of enteric bacteria modulates the extent of jejunal epithelial damage induced by doxorubicin (DXR) in mice. Despite conventional thinking of the crypt as a sterile environment, recent evidence suggests that bacterial signaling influences aISC function. In this study, we labeled aISCs using transgenic Lgr5-driven fluorescence or with immunostaining for OLFM4. We examined the effect of DXR in both germ free (GF) mice and mice depleted of microbiota using an established antimicrobial treatment protocol (AMBx). We found differences in DXR-induced loss of aISCs between GF mice and mice treated with AMBx. aISCs were decreased after DXR in GF mice, whereas AMBx mice retained aISC expression after DXR. Neither group of mice exhibited an inflammatory response to DXR, suggesting the difference in aISC retention was not due to differences in local tissue inflammation. Therefore, we suspected that there was a protective microbial signal present in the AMBx mice that was not present in the GF mice. 16S rRNA sequencing of jejunal luminal contents demonstrated that AMBx altered the fecal and jejunal microbiota. In the jejunal contents, AMBx mice had increased abundance of Ureaplasma and Burkholderia. These results suggest pro-survival signaling from microbiota in AMBx-treated mice to the aISCs, and that this signaling maintains aISCs in the face of chemotherapeutic injury. Manipulation of the enteric microbiota presents a therapeutic target for reducing the severity of chemotherapy-associated mucositis.}, number={1}, journal={GUT MICROBES}, author={Sheahan, Breanna J. and Theriot, Casey M. and Cortes, Jocsa E. and Dekaney, Christopher M.}, year={2022}, month={Dec} }
 @article{shanahan_kanke_oyesola_hung_koch-laskowski_singh_peck_biraud_sheahan_cortes_et al._2021, title={Multiomic analysis defines the first microRNA atlas across all small intestinal epithelial lineages and reveals novel markers of almost all major cell types}, volume={321}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00222.2021}, abstractNote={ In this study, first, microRNA atlas (and searchable web server) across all major small intestinal epithelial cell types is presented. We have demonstrated microRNAs that uniquely mark several lineages, including enteroendocrine and tuft. Identification of a key marker of mouse secretory progenitor cells, miR-672, which we show is deleted in humans. We have used several in vivo models to establish miR-152 as a specific marker of Paneth cells, which are highly understudied in terms of microRNAs. }, number={6}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Shanahan, Michael T. and Kanke, Matt and Oyesola, Oyebola O. and Hung, Yu-Han and Koch-Laskowski, Kieran and Singh, Ajeet P. and Peck, Bailey C. E. and Biraud, Mandy and Sheahan, Breanna and Cortes, Josca E. and et al.}, year={2021}, month={Dec}, pages={G668–G681} }
 @article{cray_sheahan_cortes_dekaney_2020, title={Doxorubicin increases permeability of murine small intestinal epithelium and cultured T84 monolayers}, volume={10}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-020-78473-1}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Cray, Paul and Sheahan, Breanna J. and Cortes, Jocsa E. and Dekaney, Christopher M.}, year={2020}, month={Dec} }
 @article{dekaney_king_sheahan_cortes_2019, title={Mist1 Expression Is Required for Paneth Cell Maturation}, volume={8}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2019.07.003}, abstractNote={Paneth cells are professional secretory cells found within the small intestinal crypt epithelium. Although their role as part of the innate immune complex providing antimicrobial secretory products is well-known, the mechanisms that control secretory capacity are not well-understood. MIST1 is a scaling factor that is thought to control secretory capacity of exocrine cells.Mist1+/+ and Mist1-/- mice were used to evaluate the function of MIST1 in small intestinal Paneth cells. We used histologic and immunofluorescence staining to evaluate small intestinal tissue for proliferation and lineage allocation. Total RNA was isolated to evaluate gene expression. Enteroid culture was used to evaluate the impact of the absence of MIST1 expression on intestinal stem cell function.Absence of MIST1 resulted in increased numbers of Paneth cells exhibiting an intermediate cell phenotype but otherwise did not alter overall epithelial cell lineage allocation. Muc2 and lysozyme staining confirmed the presence of intermediate cells at the crypt base of Mist1-/- mice. These changes were not associated with changes in mRNA expression of transcription factors associated with lineage allocation, and they were not abrogated by inhibition of Notch signaling. However, the absence of MIST1 expression was associated with alterations in Paneth cell morphology including decreased granule size and distended rough endoplasmic reticulum. Absence of MIST1 was associated with increased budding of enteroid cultures; however, there was no evidence of increased intestinal stem cell numbers in vivo.MIST1 plays an important role in organization of the Paneth cell secretory apparatus and managing endoplasmic reticulum stress. This role occurs downstream of Paneth cell lineage allocation.}, number={4}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Dekaney, Christopher M. and King, Stephanie and Sheahan, Breanna and Cortes, Jocsa E.}, year={2019}, pages={549–560} }