Medical Specialties Commons^™

Cannabinoids In Periodontology: Where Are We Now?, Yésica Carmona Rendón, Hernán Santiago Garzón, Bruno Bueno-Silva, Roger M Arce, Lina Janeth Suárez

Faculty, Staff and Student Publications

Introduction: Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's disease, arthritis, multiple sclerosis, and a range of neurodegenerative conditions. However, limited information is available regarding the therapeutic potential of cannabinoids in treating periodontal disease.

Objective: The objective of this study is to analyze the current evidence on the antibacterial and immunomodulatory effects of cannabis and its role in the healing and regeneration processes within periodontal tissues.

Results: This review discusses the potential role of cannabinoids in restoring periodontal tissue homeostasis.

Conclusions: The examination of the endocannabinoid system and the …

Exploration Of The Implementation Of An Integrated Electronic Laboratory Information Management System On Quality Diagnostics Service Indicators At A County Level Public Hospital In Western Kenya., Kelly Allen

Capstone Collection

Underinvestment in pathology and laboratory capacity caused by low visibility in research and in prioritization by public health leaders results in limited effective healthcare coverage and an estimated 1.1 million premature deaths annually in Low-and-Middle-Income Countries. Kenya’s public health laboratories provide a median 41% of the Essential Diagnostic List to their patients and in Kisumu County, as much as 44.2% of the population has little to no access to essential diagnostics. The government of Kisumu implemented the county Health Laboratory Strategic Plan 2018-2022 to address this public health challenge. Little information exists on the effectiveness of these initiatives and the …

Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma, Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford

Faculty, Staff and Student Publications

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can …

Correction: Precision Dosimetry In Yttrium-90 Radioembolization Through Ct Imaging Of Radiopaque Microspheres In A Rabbit Liver Model, E Courtney Henry, Matthew Strugari, George Mawko, Kimberly Brewer, David Liu, Andrew C Gordon, Jeffrey N Bryan, Charles Maitz, James J Karnia, Robert Abraham, S Cheenu Kappadath, Alasdair Syme

Faculty, Staff and Student Publications

No abstract provided.

Data-Driven Multiscale Model Of Macaque Auditory Thalamocortical Circuits Reproduces In Vivo Dynamics, Salvador Dura-Bernal, Erica Y Griffith, Annamaria Barczak, Monica N O'Connell, Tammy Mcginnis, Joao V S Moreira, Charles E Schroeder, William W Lytton, Peter Lakatos, Samuel A Neymotin

Faculty, Staff and Student Publications

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, …

A Heritable Iron Memory Enables Decision-Making In Escherichia Coli, Souvik Bhattacharyya, Nabin Bhattarai, Dylan M Pfannenstiel, Brady Wilkins, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This “iron” memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with …

Case Of New-Onset Scleromyxoedema-Scleroedema Spectrum Disorder In A Patient With Cll, Yuanteng Jeff Li, Victor G Prieto, Jean Tayar

Faculty, Staff and Student Publications

No abstract provided.

Single-Cell Multiomics Of The Human Retina Reveals Hierarchical Transcription Factor Collaboration In Mediating Cell Type-Specific Effects Of Genetic Variants On Gene Regulation, Jun Wang, Xuesen Cheng, Qingnan Liang, Leah A Owen, Jiaxiong Lu, Yiqiao Zheng, Meng Wang, Shiming Chen, Margaret M Deangelis, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

BACKGROUND: Systematic characterization of how genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing.

RESULTS: We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic …

Chimeric Antigen Receptor T Cells To Target Cd79b In B-Ceall Lymphomas, Fuliang Chu, Jingjing Cao, Jingwei Liu, Haopeng Yang, Timothy J Davis, Shao-Qing Kuang, Xiaoyun Cheng, Zheng Zhang, Swathi Karri, Long T Vien, Laura Bover, Ryan Sun, Francisco Vega, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas.

METHODS: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

Sustained Remissions In Cll After Frontline Fcr Treatment With Very-Long-Term Follow-Up, Philip A Thompson, Alexandre Bazinet, William G Wierda, Constantine S Tam, Susan M O'Brien, Satabdi Saha, Christine B Peterson, William Plunkett, Michael J Keating

Faculty, Staff and Student Publications

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up …

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Hyperleptinemia Contributes To Antipsychotic Drug-Associated Obesity And Metabolic Disorders, Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Joel K Elmquist, Olivia Osborn, Chen Liu, Philipp E Scherer

Faculty, Staff and Students Publications

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El1, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El13, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Distinct Transcriptomic Profiles In Children Prior To The Appearance Of Type 1 Diabetes-Linked Islet Autoantibodies And Following Enterovirus Infection, Jake Lin, Elaheh Moradi, Karoliina Salenius, Suvi Lehtipuro, Tomi Häkkinen, Jutta E Laiho, Sami Oikarinen, Sofia Randelin, Hemang M Parikh, Jeffrey P Krischer, Jorma Toppari, Åke Lernmark, Joseph F Petrosino, Nadim J Ajami, Jin-Xiong She, William A Hagopian, Marian J Rewers, Richard E Lloyd, Kirsi J Rautajoki, Heikki Hyöty, Matti Nykter, Teddy Study Group

Faculty, Staff and Students Publications

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we …

Antibody-Directed Evolution Reveals A Mechanism For Enhanced Neutralization At The Hiv-1 Fusion Peptide Site, Bailey B Banach, Sergei Pletnev, Adam S Olia, Kai Xu, Baoshan Zhang, Reda Rawi, Tatsiana Bylund, Nicole A Doria-Rose, Thuy Duong Nguyen, Ahmed S Fahad, Myungjin Lee, Bob C Lin, Tracy Liu, Mark K Louder, Bharat Madan, Krisha Mckee, Sijy O'Dell, Mallika Sastry, Arne Schön, Natalie Bui, Chen-Hsiang Shen, Jacy R Wolfe, Gwo-Yu Chuang, John R Mascola, Peter D Kwong, Brandon J Dekosky

Faculty, Staff and Student Publications

The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to …

Silencing Of Genes By Promoter Hypermethylation Shapes Tumor Microenvironment And Resistance To Immunotherapy In Clear-Cell Renal Cell Carcinomas, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Alexandra Helleux, Véronique Lindner, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Virginie Verkarre, Cheng-Ming Sun, Mostefa Bennamoun, Hervé Lang, Philippe Barthelemy, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial. High iMES is associated with VEGF pathway silencing, endothelial cell depletion, immune activation/suppression, EZH2 activation, BAP1/SETD2 deficiency, and resistance to ICI. Combination therapy with hypomethylating agents or tyrosine kinase inhibitors may benefit …

New Insights Into Yap/Taz-Tead-Mediated Gene Regulation And Biological Processes In Cancer, Yang Zhao, Marisela Sheldon, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

The Hippo pathway is conserved across species. Key mammalian Hippo pathway kinases, including MST1/2 and LATS1/2, inhibit cellular growth by inactivating the TEAD coactivators, YAP, and TAZ. Extensive research has illuminated the roles of Hippo signaling in cancer, development, and regeneration. Notably, dysregulation of Hippo pathway components not only contributes to tumor growth and metastasis, but also renders tumors resistant to therapies. This review delves into recent research on YAP/TAZ-TEAD-mediated gene regulation and biological processes in cancer. We focus on several key areas: newly identified molecular patterns of YAP/TAZ activation, emerging mechanisms that contribute to metastasis and cancer therapy resistance, …

Widespread Brca1/2-Independent Homologous Recombination Defects Are Caused By Alterations In Rna-Binding Proteins, Daniel J Mcgrail, Yang Li, Roger S Smith, Bin Feng, Hui Dai, Limei Hu, Briana Dennehey, Sharad Awasthi, Marc L Mendillo, Anil K Sood, Gordon B Mills, Shiaw-Yih Lin, S Stephen Yi, Nidhi Sahni

Faculty, Staff and Student Publications

Defects in homologous recombination DNA repair (HRD) both predispose to cancer development and produce therapeutic vulnerabilities, making it critical to define the spectrum of genetic events that cause HRD. However, we found that mutations in BRCA1/2 and other canonical HR genes only identified 10%-20% of tumors that display genomic evidence of HRD. Using a networks-based approach, we discovered that over half of putative genes causing HRD originated outside of canonical DNA damage response genes, with a particular enrichment for RNA-binding protein (RBP)-encoding genes. These putative drivers of HRD were experimentally validated, cross-validated in an independent cohort, and enriched in cancer-associated …

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong

Faculty, Staff and Students Publications

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, …

A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Deok Chun Yang, Yeon Ju Kim, Joon Hyun Song, Dong Uk Yang

Faculty, Staff and Student Publications

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species …

Prediagnostic Selenium Status, Selenoprotein Gene Variants And Association With Breast Cancer Risk In A European Cohort Study, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Veronika Fedirko, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst, Guri Skeie, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Sandra M Colorado Yohar, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Alicia K Heath, Laure Dossus

Faculty, Staff and Student Publications

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional …

Vaginal Microbial Dynamics And Pathogen Colonization In A Humanized Microbiota Mouse Model, Marlyd E Mejia, Vicki Mercado-Evans, Jacob J Zulk, Samantha Ottinger, Korinna Ruiz, Mallory B Ballard, Stephanie W Fowler, Robert A Britton, Kathryn A Patras

Faculty, Staff and Students Publications

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (

In Vivo Volumetric Depth-Resolved Imaging Of Cilia Metachronal Waves Using Dynamic Optical Coherence Tomography, Tian Xia, Kohei Umezu, Deirdre M Scully, Shang Wang, Irina V Larina

Faculty, Staff and Students Publications

Motile cilia are dynamic hair-like structures covering epithelial surfaces in multiple organs. The periodic coordinated beating of cilia creates waves propagating along the surface, known as the metachronal waves, which transport fluids and mucus along the epithelium. Motile ciliopathies result from disrupted coordinated cilia beating and are associated with serious clinical complications, including reproductive disorders. Despite the recognized clinical significance, research of cilia dynamics is extremely limited. Here, we present quantitative imaging of cilia metachronal waves volumetrically through tissue layers using dynamic optical coherence tomography (OCT). Our method relies on spatiotemporal mapping of the phase of intensity fluctuations in OCT …

Molecular Basis Of Retinal Remodeling In A Zebrafish Model Of Retinitis Pigmentosa, Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien

Faculty, Staff and Student Publications

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult zebrafish retina of wild type AB strain (WT) and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. Retinas from both female and male fish were pooled to generate each library, combining data from both sexes. …

Efficacy Of Futibatinib, An Irreversible Fibroblast Growth Factor Receptor Inhibitor, In Fgfr-Altered Breast Cancer, Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W Evans, Erkan Yuca, Stephen Scott, Bryce P Kirby, Xiaofeng Zheng, Min Jin Ha, Huiqin Chen, Patrick K S Ng, Timothy P Diperi, Gordon B Mills, Jordi Rodon Ahnert, Senthil Damodaran, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and …

The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen

Faculty, Staff and Student Publications

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into …

Dynamics Of Cwd Prion Detection In Feces And Blood From Naturally Infected White-Tailed Deer, Francisca Bravo-Risi, Paulina Soto, Rebeca Benavente, Tracy A Nichols, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervids. Confirmatory testing of CWD is currently performed postmortem in obex and lymphoid tissues. Extensive evidence demonstrates the presence of infectious prions in feces of CWD-infected deer using in vitro prion-amplification techniques and bioassays. In experimental conditions, this has been achieved as soon as 6-month post-inoculation, suggesting this sample type is a candidate for antemortem diagnosis. In the present study, we optimized the detection of CWD-prions in fecal samples from naturally infected, pre-clinical white-tailed deer by comparing protocols aiming to concentrate CWD-prions with direct spiking of the sample into the PMCA …

Revisiting The Use Of Normal Saline For Peritoneal Washing In Ovarian Cancer, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing …