@article{small_akhtari_green_havener_sikes_quintanhila_gonzalez_reif_motsinger-reif_mcleod_et al._2023, title={Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy}, volume={12}, ISSN={["2073-4409"]}, url={https://doi.org/10.3390/cells12121574}, DOI={10.3390/cells12121574}, abstractNote={Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene MKL1 displayed ethnic stratification, with the variant being significantly more prevalent in the African cohort and resulting in reduced transcript levels as measured by qPCR. Functional validation of MKL1 by shRNA-mediated knockdown of MKL1 resulted in a more resistant phenotype. Gene expression analysis identified the developmentally associated TGFB1I1 as the most significant gene associated with sensitivity. qPCR among a panel of sensitive and resistant LCLs revealed immunoglobulin class-switching as well as differences in the expression of B cell activation markers. Flow cytometry showed heterogeneity within some cell lines relative to surface Ig isotype with a shift to more IgG+ cells among the resistant lines. Pretreatment with prednisolone could partly reverse the resistant phenotype. Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.}, number={12}, journal={CELLS}, author={Small, George W. and Akhtari, Farida S. and Green, Adrian J. and Havener, Tammy M. and Sikes, Michael and Quintanhila, Julia and Gonzalez, Ricardo D. and Reif, David M. and Motsinger-Reif, Alison A. and McLeod, Howard L. and et al.}, year={2023}, month={Jun} }
 @article{harris_sikes_bergman_goller_hasley_sjogren_ramirez_gordy_2022, title={Hands-on immunology: Engaging learners of all ages through tactile teaching tools}, volume={13}, ISSN={["1664-302X"]}, url={http://dx.doi.org/10.3389/fmicb.2022.966282}, DOI={10.3389/fmicb.2022.966282}, abstractNote={Ensuring the public has a fundamental understanding of human–microbe interactions, immune responses, and vaccines is a critical challenge in the midst of a pandemic. These topics are commonly taught in undergraduate- and graduate-level microbiology and immunology courses; however, creating engaging methods of teaching these complex concepts to students of all ages is necessary to keep younger students interested when science seems hard. Building on the Tactile Teaching Tools with Guided Inquiry Learning (TTT-GIL) method we used to create an interactive lac operon molecular puzzle, we report here two TTT-GIL activities designed to engage diverse learners from middle schoolers to masters students in exploring molecular interactions within the immune system. By pairing physical models with structured activities built on the constructivist framework of Process-Oriented Guided Inquiry Learning (POGIL), TTT-GIL activities guide learners through their interaction with the model, using the Learning Cycle to facilitate construction of new concepts. Moreover, TTT-GIL activities are designed utilizing Universal Design for Learning (UDL) principles to include all learners through multiple means of engagement, representation, and action. The TTT-GIL activities reported here include a web-enhanced activity designed to teach concepts related to antibody–epitope binding and specificity to deaf and hard-of-hearing middle and high school students in a remote setting and a team-based activity that simulates the evolution of the Major Histocompatibility Complex (MHC) haplotype of a population exposed to pathogens. These activities incorporate TTT-GIL to engage learners in the exploration of fundamental immunology concepts and can be adapted for use with learners of different levels and educational backgrounds.}, journal={FRONTIERS IN MICROBIOLOGY}, publisher={Frontiers Media SA}, author={Harris, Felix R. and Sikes, Michael L. and Bergman, Michael and Goller, Carlos C. and Hasley, Andrew O. and Sjogren, Caroline A. and Ramirez, Melissa V. and Gordy, Claire L.}, year={2022}, month={Aug} }
 @article{troxell_sikes_fink_vazquez-torres_jones-carson_hassan_2011, title={Fur Negatively Regulates hns and Is Required for the Expression of HilA and Virulence in Salmonella enterica Serovar Typhimurium}, volume={193}, ISSN={["1098-5530"]}, DOI={10.1128/jb.00942-10}, abstractNote={ABSTRACT}, number={2}, journal={JOURNAL OF BACTERIOLOGY}, author={Troxell, Bryan and Sikes, Michael L. and Fink, Ryan C. and Vazquez-Torres, Andres and Jones-Carson, Jessica and Hassan, Hosni M.}, year={2011}, month={Jan}, pages={497–505} }
 @misc{azcarate-peril_sikes_bruno-barcena_2011, title={The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?}, volume={301}, ISSN={["1522-1547"]}, url={http://europepmc.org/abstract/med/21700901}, DOI={10.1152/ajpgi.00110.2011}, abstractNote={Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ( 219 ), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Azcarate-Peril, M. Andrea and Sikes, Michael and Bruno-Barcena, Jose M.}, year={2011}, month={Sep}, pages={G401–G424} }
 @article{oyegunwa_sikes_wilson_scholle_laster_2010, title={Tetra-O-methyl nordihydroguaiaretic acid (Terameprocol) inhibits the NF-kappa B-dependent transcription of TNF-alpha and MCP-1/CCL2 genes by preventing RelA from binding its cognate sites on DNA}, volume={7}, ISSN={["1476-9255"]}, DOI={10.1186/1476-9255-7-59}, abstractNote={Abstract}, journal={JOURNAL OF INFLAMMATION-LONDON}, author={Oyegunwa, Akinbolade O. and Sikes, Michael L. and Wilson, Jason R. and Scholle, Frank and Laster, Scott M.}, year={2010}, month={Dec} }
 @misc{sikes_mcmillan_bradshaw_2010, title={The Center of Accessibility: D beta Control of V(D)J Recombination}, volume={58}, ISSN={["0004-069X"]}, DOI={10.1007/s00005-010-0101-2}, abstractNote={Developmental patterning of antigen receptor gene assembly in lymphocyte precursors correlates with decondensation of the chromatin surrounding individual gene segments. Ongoing V(D)J recombination is associated with hyperacetylation of histones H3 and H4 and the expression of sterile germline transcripts across the region of recombinational accessibility. Likewise, histone acetyltransferase and SWI/SNF chromatin remodeling complexes each appear to be required for recombination, and the PHD-finger of RAG-2 preferentially associates with recombination signal sequence (RSS) chromatin that contains H3 trimethylated on lysine 4. However, the regulatory mechanisms that direct chromatin alteration and rearrangement have proven elusive, due in large part to the interdependency of individual stages in gene activation, our limited understanding of functional significance of changes to the histone code, and the difficulty of modeling recombinational accessibility in existing experimental systems. Examining Tcrb assembly in developing thymocytes, we review the central roles of RSS elements and germline promoters as foci for epigenetic reorganization of recombinationally accessible gene segments in light of recent findings and persistent questions.}, number={6}, journal={ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS}, author={Sikes, Michael L. and McMillan, Ruth E. and Bradshaw, Justin M.}, year={2010}, month={Dec}, pages={427–433} }
 @article{sikes_bradshaw_ivory_lunsford_mcmillan_morrison_2009, title={A streamlined method for rapid and sensitive chromatin immunoprecipitation}, volume={344}, ISSN={["0022-1759"]}, DOI={10.1016/j.jim.2009.03.007}, abstractNote={We report a streamlined procedure to efficiently carry samples from chromatin to qPCR-compatible DNA in as little as 4 h. We use this streamlined ChIP to quantify histone H3 modifications at active (cad) and repressed (T early alpha) promoters in a Rag1-deficient pro-T cell line after 1–2 h IP. We further show that the protocol readily quantified histone modifications in chromatin from 104 Rag-deficient DN thymocytes. Taken together, these data outline a simple, cost-effective procedure for efficient ChIP analysis.}, number={1}, journal={JOURNAL OF IMMUNOLOGICAL METHODS}, author={Sikes, Michael L. and Bradshaw, Justin M. and Ivory, Wendell T. and Lunsford, Jessica L. and McMillan, Ruth E. and Morrison, Clayton R.}, year={2009}, month={May}, pages={58–63} }
 @article{taveirne_sikes_olson_2009, title={Molybdenum and tungsten in Campylobacter jejuni: their physiological role and identification of separate transporters regulated by a single ModE-like protein}, volume={74}, ISSN={["1365-2958"]}, DOI={10.1111/j.1365-2958.2009.06901.x}, abstractNote={Summary}, number={3}, journal={MOLECULAR MICROBIOLOGY}, author={Taveirne, Michael E. and Sikes, Michael L. and Olson, Jonathan W.}, year={2009}, month={Nov}, pages={758–771} }
 @article{mcmillan_sikes_2009, title={Promoter activity 5 ' of D beta 2 is coordinated by E47, Runx1, and GATA-3}, volume={46}, ISSN={["0161-5890"]}, DOI={10.1016/j.molimm.2009.06.013}, abstractNote={V(D)J recombination involves the stepwise assembly of B and T cell receptor genes as lymphocytes progress through the early stages of development. While the mechanisms that restrict each step in recombination to its appropriate developmental stage are largely unknown, they share many of the components that regulate transcription. For example, enhancer-dependent modifications in histone acetylation and methylation are essential for both germline transcription and rearrangement of antigen receptor genes. Promoters positioned proximal to individual D and J gene segments in Tcra, Tcrb, Tcrd, IgH, and Igk also contribute to antigen receptor gene assembly, though their effects appear more localized than those of enhancers. Tcrb assembly initiates with D-to-J joining at each of the two D-J-C gene segment clusters in DN1/2 thymocytes. DJ joints are fused with Vbeta elements to complete Tcrb recombination in DN3 cells. We have previously shown that Dbeta2 is flanked by upstream and downstream promoters, with the 5' promoter being held inactive until D-to-J recombination deletes the NFkappaB-dependent 3' promoter. We now report that activity of the 5' promoter reflects a complex interplay among Runx1, GATA-3, and E47 transcription factors. In particular, while multiple E47 and Runx1 binding sites clustered near the Dbeta2 5'RS and overlapping inr elements define the core 5'PDbeta2, they act in concert with an array of upstream GATA-3 sites to overcome the inhibitory effects of a 110bp distal polypurine.polypyrimidine (R.Y) tract. The dependence of 5'PDbeta2 on E47 is consistent with the reported role of E proteins in post-DN1 thymocyte development and V-to-DJbeta recombination.}, number={15}, journal={MOLECULAR IMMUNOLOGY}, author={McMillan, Ruth E. and Sikes, Michael L.}, year={2009}, month={Sep}, pages={3009–3017} }
 @article{mcmillan_sikes_2008, title={Differential activation of dual promoters alters D beta 2 germline transcription during thymocyte development}, volume={180}, ISSN={["0022-1767"]}, DOI={10.4049/jimmunol.180.5.3218}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF IMMUNOLOGY}, author={McMillan, Ruth E. and Sikes, Michael L.}, year={2008}, month={Mar}, pages={3218–3228} }