Medicine and Health Sciences Commons^™

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

A Recombinant Murine-Like Rotavirus With Nano-Luciferase Expression Reveals Tissue Tropism, Replication Dynamics, And Virus Transmission, Yinxing Zhu, Liliana Sánchez-Tacuba, Gaopeng Hou, Takahiro Kawagishi, Ningguo Feng, Harry B Greenberg, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses (RVs) are one of the main causes of severe gastroenteritis, diarrhea, and death in children and young animals. While suckling mice prove to be highly useful small animal models of RV infection and pathogenesis, direct visualization tools are lacking to track the temporal dynamics of RV replication and transmissibility

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Uveitis-Mediated Immune Cell Invasion Through The Extracellular Matrix Of The Lens Capsule, Jodirae Dedreu, Sonali Pal-Ghosh, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Classical And Γδ T Cells Are Each Independently Sufficient To Establish Protection Against A Classical Strain Of Klebsiella Pneumoniae, Joseph J Mackel, Catherine Morffy Smith, Rachel K Wasbotten, Joy Twentyman, David A Rosen

2020-Current year OA Pubs

Infections with classical strains of the Gram-negative bacterium

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …