@article{zwarycz_gracz_rivera_williamson_samsa_starmer_daniele_salter-cid_zhao_magness_2019, title={IL22 Inhibits Epithelial Stem Cell Expansion in an Ileal Organoid Model}, volume={7}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2018.06.008}, abstractNote={Crohn's disease is an inflammatory bowel disease that affects the ileum and is associated with increased cytokines. Although interleukin (IL)6, IL17, IL21, and IL22 are increased in Crohn's disease and are associated with disrupted epithelial regeneration, little is known about their effects on the intestinal stem cells (ISCs) that mediate tissue repair. We hypothesized that ILs may target ISCs and reduce ISC-driven epithelial renewal.A screen of IL6, IL17, IL21, or IL22 was performed on ileal mouse organoids. Computational modeling was used to predict microenvironment cytokine concentrations. Organoid size, survival, proliferation, and differentiation were characterized by morphometrics, quantitative reverse-transcription polymerase chain reaction, and immunostaining on whole organoids or isolated ISCs. ISC function was assayed using serial passaging to single cells followed by organoid quantification. Single-cell RNA sequencing was used to assess Il22ra1 expression patterns in ISCs and transit-amplifying (TA) progenitors. An IL22-transgenic mouse was used to confirm the impact of increased IL22 on proliferative cells in vivo.High IL22 levels caused decreased ileal organoid survival, however, resistant organoids grew larger and showed increased proliferation over controls. Il22ra1 was expressed on only a subset of ISCs and TA progenitors. IL22-treated ISCs did not show appreciable differentiation defects, but ISC biomarker expression and self-renewal-associated pathway activity was reduced and accompanied by an inhibition of ISC expansion. In vivo, chronically increased IL22 levels, similar to predicted microenvironment levels, showed increases in proliferative cells in the TA zone with no increase in ISCs.Increased IL22 limits ISC expansion in favor of increased TA progenitor cell expansion.}, number={1}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Zwarycz, Bailey and Gracz, Adam D. and Rivera, Kristina R. and Williamson, Ian A. and Samsa, Leigh A. and Starmer, Josh and Daniele, Michael A. and Salter-Cid, Luisa and Zhao, Qihong and Magness, Scott T.}, year={2019}, pages={1–17} }
 @article{sivamani_starmer_qu_2009, title={Sequence analysis of rice rubi3 promoter gene expression cassettes for improved transgene expression}, volume={177}, ISSN={["0168-9452"]}, DOI={10.1016/j.plantsci.2009.08.006}, abstractNote={In a construct containing a GUS reporter gene driven by the 5′ regulatory elements from rubi3, expression was enhanced 4-fold when a 20-nucleotide (nt) GUS 5′ untranslated sequence was replaced with 9 nt sequences derived from rubi3′s second exon. The roles of the sequences immediately upstream from the GUS translation initiation codon, and their significance in gene expression, were investigated. Sequence analysis suggests that complementarity between sequences immediately 5′ of a translation initiation codon and the rice 17S rRNA may be responsible for the reduction in protein levels from constructs containing the GUS leader sequence. The results demonstrate an affect sequences immediately upstream from transgenic coding sequences have on expression, and when using the rubi3 5′ regulatory sequence in particular.}, number={6}, journal={PLANT SCIENCE}, author={Sivamani, Elumalai and Starmer, Joshua D. and Qu, Rongda}, year={2009}, month={Dec}, pages={549–556} }
 @article{starmer_stomp_vouk_bitzer_2006, title={Predicting Shine-Dalgarno sequence locations exposes genome annotation errors}, volume={2}, ISSN={["1553-7358"]}, DOI={10.1371/journal.pcbi.0020057}, abstractNote={In prokaryotes, Shine–Dalgarno (SD) sequences, nucleotides upstream from start codons on messenger RNAs (mRNAs) that are complementary to ribosomal RNA (rRNA), facilitate the initiation of protein synthesis. The location of SD sequences relative to start codons and the stability of the hybridization between the mRNA and the rRNA correlate with the rate of synthesis. Thus, accurate characterization of SD sequences enhances our understanding of how an organism's transcriptome relates to its cellular proteome. We implemented the Individual Nearest Neighbor Hydrogen Bond model for oligo–oligo hybridization and created a new metric, relative spacing (RS), to identify both the location and the hybridization potential of SD sequences by simulating the binding between mRNAs and single-stranded 16S rRNA 3′ tails. In 18 prokaryote genomes, we identified 2,420 genes out of 58,550 where the strongest binding in the translation initiation region included the start codon, deviating from the expected location for the SD sequence of five to ten bases upstream. We designated these as RS+1 genes. Additional analysis uncovered an unusual bias of the start codon in that the majority of the RS+1 genes used GUG, not AUG. Furthermore, of the 624 RS+1 genes whose SD sequence was associated with a free energy release of less than −8.4 kcal/mol (strong RS+1 genes), 384 were within 12 nucleotides upstream of in-frame initiation codons. The most likely explanation for the unexpected location of the SD sequence for these 384 genes is mis-annotation of the start codon. In this way, the new RS metric provides an improved method for gene sequence annotation. The remaining strong RS+1 genes appear to have their SD sequences in an unexpected location that includes the start codon. Thus, our RS metric provides a new way to explore the role of rRNA–mRNA nucleotide hybridization in translation initiation.}, number={5}, journal={PLOS COMPUTATIONAL BIOLOGY}, author={Starmer, J. and Stomp, A. and Vouk, M. and Bitzer, D.}, year={2006}, month={May}, pages={454–466} }