Digital Commons Network^™

Lacrimal Gland Epithelial Cells Shape Immune Responses Through The Modulation Of Inflammasomes And Lipid Metabolism, Vanessa Delcroix, Olivier Mauduit, Menglu Yang, Amrita Srivastava, Takeshi Umazume, Cintia S De Paiva, Valery I Shestopalov, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased

Comparison Of Dna Extraction Methods For Soft Tissue Samples, Steve Guzman, Nathaniel E. Hill, Mujtaba Shah, Jonathon Reynolds, Cole Farnsworth, Molly Henley, Alfred Amendolara, Laura Minor, John Dougherty Jr., John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

The Effects Of Vitamin B1 Analog, Benfotiamine, On The Prevention Of Non-Small Cell Lung Cancer, Emely Fernandez, Hannah Christensen, Kota A. Ramana

Annual Research Symposium

No abstract provided.

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In Rat Lung, Liver, Spleen And Blood, Yensi Munoz

Annual Research Symposium

No abstract provided.

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

A Composition Of Phytonutrients For Glycemic And Weight Management, Yasuyo Urasaki

Annual Research Symposium

No abstract provided.

Mclena-1: A Phase Ii Clinical Trial For The Assessment Of Safety, Tolerability, And Efficacy Of Lenalidomide In Patients With Mild Cognitive Impairment Due To Alzheimer's Disease; Trial Design And Rationale, Boris Decourt

Annual Research Symposium

No abstract provided.

The Use Of Art History In The Study Of Histology Images By Medical Students, Madeleine Karpiuk

Annual Research Symposium

No abstract provided.

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, Gimenez-Lirola Baum, Locke A. Karriker

Nebraska Center for Virology: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Differential Regulation Of H3k9/H3k14 Acetylation By Small Molecules Drives Neuron-Fate-Induction Of Glioma Cell, Xincheng Liu, Cui Guo, Tiandong Leng, Zhen Fan, Jialuo Mai, Jiehong Chen, Jinhai Xu, Qianyi Li, Bin Jiang, Ke Sai, Wenzhuo Yang, Jiayu Gu, Jingyi Wang, Shuxin Sun, Zhijie Chen, Yingqian Zhong, Xuanming Liang, Chaoxin Chen, Jing Cai, Yuan Lin, Jiankai Liang, Jun Hu, Guangmei Yan, Wenbo Zhu, Wei Yin

Faculty, Staff and Student Publications

Differentiation therapy using small molecules is a promising strategy for improving the prognosis of glioblastoma (GBM). Histone acetylation plays an important role in cell fate determination. Nevertheless, whether histone acetylation in specific sites determines GBM cells fate remains to be explored. Through screening from a 349 small molecule-library, we identified that histone deacetylase inhibitor (HDACi) MS-275 synergized with 8-CPT-cAMP was able to transdifferentiate U87MG GBM cells into neuron-like cells, which were characterized by cell cycle arrest, rich neuron biomarkers, and typical neuron electrophysiology. Intriguingly, acetylation tags of histone 3 at lysine 9 (H3K9ac) were decreased in the promoter of multiple …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Conditioned Place Avoidance Is Associated With A Distinct Hippocampal Phenotype, Partly Preserved Pattern Separation, And Reduced Reactive Oxygen Species Production After Stress, D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S.V.P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V.G. Katakam, Nicholas W. Gilpin, Joseph Francis

School of Medicine Faculty Publications

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated …

Exploiting Metabolic Vulnerabilities After Anti-Vegf Antibody Therapy In Ovarian Cancer, Deanna Glassman, Mark S Kim, Meredith Spradlin, Sunil Badal, Mana Taki, Pratip Bhattacharya, Prasanta Dutta, Charles V Kingsley, Katherine I Foster, Olamide Animasahun, Jin Heon Jeon, Abhinav Achreja, Anusha Jayaraman, Praveen Kumar, Minal Nenwani, Fulei Wuchu, Emine Bayraktar, Yutuan Wu, Elaine Stur, Lingegowda Mangala, Sanghoon Lee, Timothy A Yap, Shannon N Westin, Livia S Eberlin, Deepak Nagrath, Anil K Sood

Faculty, Staff and Student Publications

Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence …

Alternative Polyadenylation Alters Protein Dosage By Switching Between Intronic And 3’Utr Sites, Nicola De Prisco, Caitlin Ford, Nathan D Elrod, Winston Lee, Lauren C Tang, Kai-Lieh Huang, Ai Lin, Ping Ji, Venkata S Jonnakuti, Lia Boyle, Maximilian Cabaj, Salvatore Botta, Katrin Õunap, Karit Reinson, Monica H Wojcik, Jill A Rosenfeld, Weimin Bi, Kristian Tveten, Trine Prescott, Thorsten Gerstner, Audrey Schroeder, Chin-To Fong, Jaya K George-Abraham, Catherine A Buchanan, Andrea Hanson-Khan, Jonathan A Bernstein, Aikaterini A Nella, Wendy K Chung, Vicky Brandt, Marko Jovanovic, Kimara L Targoff, Hari Krishna Yalamanchili, Eric J Wagner, Vincenzo A Gennarino

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function …

Batf2 Promotes Hsc Myeloid Differentiation By Amplifying Ifn Response Mediators During Chronic Infection, Duy T Le, Marcus A Florez, Pawel Kus, Brandon T Tran, Bailee Kain, Yingmin Zhu, Kurt Christensen, Antrix Jain, Anna Malovannaya, Katherine Y King

Faculty, Staff and Students Publications

Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key factor responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism of BATF2 function in HSCs, we assessed Batf2 KO mice during chronic infection and found that they produced less pro-inflammatory cytokines, less immune cell recruitment to the spleen, and impaired myeloid differentiation with better preservation of HSC capacity compared to WT. Co-IP analysis revealed that BATF2 forms a complex with JUN to amplify pro-inflammatory signaling pathways including CCL5 during infection. Blockade of CCL5 receptors phenocopied Batf2 KO differentiation …

Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang

Faculty, Staff and Student Publications

Constant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. …

Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Faculty, Staff and Student Publications

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …

Drug-Like Small Molecules That Inhibit Expression Of The Oncogenic Microrna-21, Matthew D Shortridge, Bhawna Chaubey, Huanyu J Zhang, Thomas Pavelitz, Venkata Vidadala, Changyan Tang, Gregory L Olsen, George A Calin, Gabriele Varani

Faculty, Staff and Student Publications

We report the discovery of drug-like small molecules that bind specifically to the precursor of the oncogenic and pro-inflammatory microRNA-21 with mid-nanomolar affinity. The small molecules target a local structure at the Dicer cleavage site and induce distinctive structural changes in the RNA, which correlate with specific inhibition of miRNA processing. Structurally conservative single nucleotide substitutions eliminate the conformational change induced by the small molecules, which is also not observed in other miRNA precursors. The most potent of these compounds reduces cellular proliferation and miR-21 levels in cancer cell lines without inhibiting kinases or classical receptors, while closely related compounds …

A Human Stem Cell-Derived Neuronal Model Of Morphine Exposure Reflects Brain Dysregulation In Opioid Use Disorder: Transcriptomic And Epigenetic Characterization Of Postmortem-Derived Ipsc Neurons, Emily F Mendez, Sandra L Grimm, Laura Stertz, Damian Gorski, Sai V Movva, Katherine Najera, Karla Moriel, Thomas D Meyer, Gabriel R Fries, Cristian Coarfa, Consuelo Walss-Bass

Faculty, Staff and Student Publications

INTRODUCTION: Human-derived induced pluripotent stem cell (iPSC) models of brain promise to advance our understanding of neurotoxic consequences of drug use. However, how well these models recapitulate the actual genomic landscape and cell function, as well as the drug-induced alterations, remains to be established. New

METHODS: We engineered a novel induced pluripotent stem cell-derived model of neural progenitor cells and neurons from cultured postmortem human skin fibroblasts, and directly compared these to isogenic brain tissue from the donor source. We assessed the maturity of the cell models across differentiation from stem cells to neurons using RNA cell type and maturity …

Emergent Dynamics Of Adult Stem Cell Lineages From Single Nucleus And Single Cell Rna-Seq Of Drosophila Testes, Amelie A Raz, Gabriela S Vida, Sarah R Stern, Sharvani Mahadevaraju, Jaclyn M Fingerhut, Jennifer M Viveiros, Soumitra Pal, Jasmine R Grey, Mara R Grace, Cameron W Berry, Hongjie Li, Jasper Janssens, Wouter Saelens, Zhantao Shao, Chun Hu, Yukiko M Yamashita, Teresa Przytycka, Brian Oliver, Julie A Brill, Henry Krause, Erika L Matunis, Helen White-Cooper, Stephen Dinardo, Margaret T Fuller

Faculty, Staff and Students Publications

Proper differentiation of sperm from germline stem cells, essential for production of the next generation, requires dramatic changes in gene expression that drive remodeling of almost all cellular components, from chromatin to organelles to cell shape itself. Here, we provide a single nucleus and single cell RNA-seq resource covering all of spermatogenesis in Drosophila starting from in-depth analysis of adult testis single nucleus RNA-seq (snRNA-seq) data from the Fly Cell Atlas (FCA) study. With over 44,000 nuclei and 6000 cells analyzed, the data provide identification of rare cell types, mapping of intermediate steps in differentiation, and the potential to identify …

Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting …

Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When …

Decreasing Mutant Atxn1 Nuclear Localization Improves A Spectrum Of Sca1-Like Phenotypes And Brain Region Transcriptomic Profiles, Hillary P Handler, Lisa Duvick, Jason S Mitchell, Marija Cvetanovic, Molly Reighard, Alyssa Soles, Kathleen B Mather, Orion Rainwater, Shannah Serres, Tessa Nichols-Meade, Stephanie L Coffin, Yun You, Brian L Ruis, Brennon O'Callaghan, Christine Henzler, Huda Y Zoghbi, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a dominant trinucleotide repeat neurodegenerative disease characterized by motor dysfunction, cognitive impairment, and premature death. Degeneration of cerebellar Purkinje cells is a frequent and prominent pathological feature of SCA1. We previously showed that transport of ATXN1 to Purkinje cell nuclei is required for pathology, where mutant ATXN1 alters transcription. To examine the role of ATXN1 nuclear localization broadly in SCA1-like disease pathogenesis, CRISPR-Cas9 was used to develop a mouse with an amino acid alteration (K772T) in the nuclear localization sequence of the expanded ATXN1 protein. Characterization of these mice indicates that proper nuclear localization …

Molecular Diagnosis Of Non X-Linked Ectodermal Dysplasias Using Next Generation Sequencing, Eman Abdelalim Rabie

Theses and Dissertations

Ectodermal Dysplasias (EDs) are rare heterogenous monogenic developmental disorders sharing the impairment of at least two surface ectoderm-derived organs. Symptoms characteristically manifest developmental abnormalities of the teeth, and three skin derivatives: hair follicles, nails, and sweat glands. The disease-causing gene was identified for only fewer than half of 160 characterized ED phenotypes. Expectedly, ED-causing genes regulate or function in ectodermal-developmental processes. The most common phenotype is hypohidrotic ED featuring teeth agenesis, and diminished or complete absence of hair and sweat production. Disease-causing variants of EDA, EDAR, EDARADD and WNT10A genes were identified in 60-90% of ED patients in …

Disruption Of The Atxn1-Cic Complex Reveals The Role Of Additional Nuclear Atxn1 Interactors In Spinocerebellar Ataxia Type 1, Stephanie L Coffin, Mark A Durham, Larissa Nitschke, Eder Xhako, Amanda M Brown, Jean-Pierre Revelli, Esmeralda Villavicencio Gonzalez, Tao Lin, Hillary P Handler, Yanwan Dai, Alexander J Trostle, Ying-Wooi Wan, Zhandong Liu, Roy V Sillitoe, Harry T Orr, Huda Y Zoghbi

Faculty, Staff and Students Publications

Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative disease in that it is caused by a mutation in a broadly expressed protein, ATXN1; however, only select populations of cells degenerate. The interaction of polyglutamine-expanded ATXN1 with the transcriptional repressor CIC drives cerebellar Purkinje cell pathogenesis; however, the importance of this interaction in other vulnerable cells remains unknown. Here, we mutated the 154Q knockin allele of Atxn1154Q/2Q mice to prevent the ATXN1-CIC interaction globally. This normalized genome-wide CIC binding; however, it only partially corrected transcriptional and behavioral phenotypes, suggesting the involvement of additional factors in disease pathogenesis. Using unbiased …

Cxcr4 Expression Is Associated With Proneural-To-Mesenchymal Transition In Glioblastoma, A Basit Khan, Sungho Lee, Akdes Serin Harmanci, Rajan Patel, Khatri Latha, Yuhui Yang, Anantha Marisetty, Hyun-Kyoung Lee, Amy B Heimberger, Gregory N Fuller, Benjamin Deneen, Ganesh Rao

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as …

Ush2a Mutation And Specific Driver Mutation Subtypes Are Associated With Clinical Efficacy Of Immune Checkpoint Inhibitors In Lung Cancer, Dexin Yang, Yuqin Feng, Haohua Lu, Kelie Chen, Jinming Xu, Peiwei Li, Tianru Wang, Dajing Xia, Yihua Wu

Faculty, Staff and Student Publications

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog

Combination Of Epha2- And Wee1-Targeted Therapies In Endometrial Cancer, Santosh K Dasari, Robiya Joseph, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial …

A Novel Sorbicillinoid Compound As A Potent Anti‐Inflammation Agent Through Inducing Nlrp3 Protein Degradation, Fangfang Wang, Youwei Zhang

Faculty Scholarship

Background and Purpose: Chronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain‐containing protein 3 (NLRP3) is the best‐characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health. Experimental Approach: Lipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/d‐galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme‐linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in …