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The Legal Philosophy Behind Zoos Confinement Of Animals, Jamie Lynn Tucker Crockett

Undergraduate Theses, Professional Papers, and Capstone Artifacts

In my essay, I will be diving into the controversial issue of Animal containment, focusing on zoos in the United States. I will be taking this opportunity to establish a new way of thinking about the argument which states the pros of zoos outweigh the negative effects they have on the animals who live there. Neither side of the argument has a malicious intention towards harming animals. Instead, each side shows a different approach of what it is to properly care, and respect for animal rights. Those arguing in support of zoos commonly reference arguments dating back to Aristotle. However, …

Peculiarities Of Phosphatidylserine Externalization By Nano- And Microsecond Electric Pulses, Mantas Silkunas, Alayna Enos, Iurii Semenov, Giedre Silkuniene, Eleni Zivla, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

Phosphatidylserine (PS) externalization is a hallmark of apoptosis but can also be triggered within seconds by pulsed electric fields (PEFs). Whether PS reaches the outer leaflet by lateral migration through electropores or indirectly through Ca²⁺-dependent signaling and scramblase activation remains debated. We used total internal reflection fluorescence (TIRF) microscopy with Annexin V-Alexa Fluor 568 and/or bovine lactadherin-FITC to resolve PS externalization in HEK293 cells placed on an indium tin oxide (ITO) transparent electrode. PEF exposures produced discrete PS-positive puncta ("freckles") within ~ 10 s after a 20-µs pulse (1.2-2.5 kV/cm) or with a ~ 1-min delay after a …

Pharmacogenetic Hslco1b1*14-Guided Dosing Of Methotrexate In Transgenic Arthritic Mice Normalizes Exposure And Response., Felicia Gooden, Brennan D. Meier, Griffin D. Shaffer, Kim Gibson, Paul Toren, Nieko C. Punt, Sandhya Subash, Dilip K. Singh, Bhagwat Prasad, Laura Ramsey, Zachary L. Taylor

Manuscripts, Articles, Book Chapters and Other Papers

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease that negatively affects ~100,000 children under the age of 16 in the United States. About ~30% of these patients fail first-line drug therapy with low-dose methotrexate (MTX) due to poor tolerability or lack of efficacy. The SLCO1B1*14 allele is associated with increased MTX clearance and has been linked to reduced overall drug exposure and nonresponse to MTX in JIA patients. Herein, we describe transgenic hSLCO1B1*14 and hSLCO1B1*1 DBA1/J mSlco1b2 knock-out mice, which we used to assess arthritic response to MTX using the collagen-induced arthritis model. Mass spectrometry-based proteomics analysis revealed that …

Bovine Lactoferrin Maintains Antibacterial Effect Against Neonatal Escherichia Coli Septicaemia Isolates Despite The Presence Of Iron Acquisition Genes, Matthew Mayorga, Joshua Wheatley, Brianna N. Maldonado, Susana Chavez-Bueno

Manuscripts, Articles, Book Chapters and Other Papers

Introduction. Escherichia coli is a dominant cause of neonatal sepsis for which no prevention measures currently exist. Lactoferrin (LF) is an iron-sequestering antibacterial protein that has been noticed to decrease neonatal late-onset sepsis.Hypothesis/Gap Statement. LF's effect on in vitro growth of neonatal E. coli clinical isolates causing septicaemia is unknown. The prevalence of iron acquisition virulence genes which contribute to pathogenicity outcomes in these strains has also not been described in detail.Aim. To evaluate bovine lactoferrin's (bLF) effects on the in vitro growth of neonatal septicaemia E. coli isolates, and to determine the presence of iron acquisition virulence …

Identification Of Neural Crest And Melanoma Cancer Cell Invasion And Migration Genes Using High-Throughput Screening And Deep Attention Networks., J C Kasemeier-Kulesa, S Martina Perez, R E Baker, Paul M. Kulesa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cell migration and invasion are well-coordinated in development and disease but remain poorly understood. We previously showed that the neural crest (NC) cell migratory wavefront shares a 45-gene panel with other cell invasion phenomena. To rapidly and systematically identify critical genes, we performed a high-throughput siRNA screen and statistical and deep learning analyses to determine changes in NC- versus non-NC-derived human cell line behaviors.

RESULTS: We find 14 out of 45 genes significantly reduced c8161 melanoma cell migration; four of the 14 genes altered leader cell motility (BMP4, ITGB1, KCNE3, and RASGRP1). Deep learning identified marked disruptions in cell-neighbor …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Markov Chain Wave Generative Adversarial Network For Bee Bioacoustic Signal Synthesis, Kumudu Samarappuli, Iman Ardekani, Mahsa Mohaghegh, Abdolhossein Sarrafzadeh

Electrical & Computer Engineering Faculty Publications

This paper presents a framework for synthesizing bee bioacoustic signals associated with hive events. While existing approaches like WaveGAN have shown promise in audio generation, they often fail to preserve the subtle temporal and spectral features of bioacoustic signals critical for event-specific classification. The proposed method, MCWaveGAN, extends WaveGAN with a Markov Chain refinement stage, producing synthetic signals that more closely match the distribution of real bioacoustic data. Experimental results show that this method captures signal characteristics more effectively than WaveGAN alone. Furthermore, when integrated into a classifier, synthesized signals improved hive status prediction accuracy. These results highlight the potential …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Immortalization And Characterization Of Schwann Cell Lines Derived From Nf1-Associated Cutaneous Neurofibromas, Hua Li, Angela Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant in the NF1 gene. The most characteristic feature of the condition NF1 is the neurofibroma, a benign, multi-cellular tumor which initiates when a cell of the Schwann cell lineage gains a somatic pathogenic variant of the other NF1 allele. Neurofibromas developing at nerve termini in the skin are termed "cutaneous" neurofibromas (cNFs), while those developing within larger nerves are termed "plexiform." Most patients develop cNFs beginning in late childhood or early adulthood, continuing throughout life at variable rates. Some patients may …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Cutibacterium Adaptation To Life On Humans Provides A Potential C Acnes Infection Biomarker, Md Shafiuddin, Wen-Chi Huang, Gabriel William Prather, Jeffrey Ryan Anton, Andrew Lawrence Martin, Sydney Brianna Sillart, Jonathan Z Tang, Michael R Vittori, Michael J Prinsen, Jessica Jane Ninneman, Chandrashekhara Manithody, Jeffrey P Henderson, Alexander W Aleem, Ma Xenia Garcia Ilagan, William H Mccoy 4th

2020-Current year OA Pubs

Propionibacteriaceae appear to have adapted to life on humans during the domestication of cattle. These microbial immigrants formed the genus Cutibacterium, and a descendent of those microbial trailblazers (C acnes) now dominates 25% of human skin. C acnes colonization of human skin requires the protein RoxP. Although all Cutibacteria encode this adaptation to life on humans, nothing like RoxP has been found in any other organism. In this study, we report an extensive assessment of 21 RoxP orthologs, which identified conserved molecular surfaces linked to heme-dependent oligomerization and low pH stability. Our investigation suggests how RoxP helps C acnes dominate …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

Dysregulated Lactate Metabolism Synergizes With Als Genetic Risk Factors To Accelerate Motor Decline, Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Neurons rely on glial 'lactate shuttling' for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

A Microenvironment-Driven Hla-Ii-Associated Insulin Neoantigen Elicits Persistent Memory T Cell Activation In Diabetes, Neetu Srivastava, Anthony N Vomund, Rongzhen Yu, Orion J Peterson, Yuqing Yang, David P Turicek, Omar Abousaway, Tiandao Li, Pamela Stone, Aisha Ansar, Rima Melhem, Bo Zhang, Chang Liu, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Emil R Unanue, Ana Maria Arbelaez, Cheryl F Lichti, Xiaoxiao Wan, Et Al.

2020-Current year OA Pubs

The antigenic landscape of autoimmune diabetes reflects a failure to preserve self-tolerance, yet how novel neoantigens emerge in humans remains incompletely understood. Here we designed an immunopeptidomics-based approach to probe HLA-II-bound, islet-derived neoepitopes in patients with type 1 diabetes. We uncovered a Cys→Ser transformation, conserved between mice and humans, that reshapes autoreactivity to insulin at the single-residue level. This transformation, which we call C19S, arises from oxidative remodeling of insulin in stressed pancreatic islets and also occurs in cytokine-activated antigen-presenting cells, contributing to a feed-forward loop of neoepitope formation and presentation. Despite involving just one amino acid, C19S is recognized …

Nanofibrous Materials And Nanoparticles For Combating Antimicrobial Resistance: Synthesis, Integration, And Translational Perspectives, Rewati Raman Ujjwal, Ashish Dilip Sutar, Rahul Shukla, Gymama Slaughter

Center for Bioelectronics Publications

Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered …

An Anti-Adhesive Compound Modulating The Production Of Staphylococcus Aureus Cell Wall-Anchored Proteins, Allison C. Leonard, Ruina Bao, Cindy Menjivar, Megan J. Myers, Telmo O. Paiva, Zhiyong Zheng, Kirsten A. Berry, Kenneth W. Bayles, Ronald S. Flannagan, Yves F. Dufrêne, Jeffrey L. Bose, David E. Heinrichs, Georgina Cox

Journal Articles: Pathology and Microbiology

As one of the leading global causes of death associated with antimicrobial resistance, Staphylococcus aureus frequently colonizes the human nasal cavity and adheres to keratinized skin, establishing reservoirs that drive subsequent infections and emphasize the need for new decolonization strategies. Using a high-throughput, whole-cell screening platform, here we identify geranylgeranoic acid (GGA), a naturally occurring polyunsaturated, branched-chain fatty acid, as having dual activity against methicillin-resistant S. aureus (MRSA). At elevated concentrations, GGA exhibits microbicidal effects, whereas at sub‑microbicidal doses, it effectively inhibits MRSA adhesion to keratin, fibronectin, fibrinogen, and immunoglobulins. GGA possesses anti-adhesive activity against a panel of multidrug-resistant S. …

Bulletin 4936: Guidelines To Importing And Keeping Regulated Animals In Western Australia, Win Kirkpatrick

Bulletins 4000 -

Updated:

• January 2026 after a review of permit keeping conditions.
• December 2025 for transfer of restricted keeping bird permit business to DPIRD.

Introduced, exotic or alien animals are species that have been brought to a country or location where they do not occur naturally. (Hereafter referred to as introduced species). Mammals, birds, reptiles, and amphibians that are introduced or relocated to new areas often cause problems to agriculture, the environment and the community. Problems occur when introduced species:

• damage agricultural crops
• displace and compete with native animals and plants
• carry disease or parasites
• damage property
• cause land degradation
• have a …

The Rna-Binding Protein Pumilio Limits Polymodal Noiception In Drosophila Larvae, Sara Palega, Hannah Davenport, Rebeccah K. Stewart, Jessica Horton, Andrew Bellemer

Microbiology & Molecular Cell Biology Faculty Publications

Nociception is the process by which the nervous system detects and processes information about potentially harmful environmental stimuli to generate behavioral and physiological responses. The process of nociception undergoes plasticity in response to injury, inflammation, and infection to shape the sensitivity of nociceptive circuits and the behavioral responses they control. We are increasingly aware that post-transcriptional regulation of gene expression shapes the sensitivity and plasticity of nociceptive sensory neurons and nociceptive behavior. In Drosophila, the Pumilio RNA-binding protein interacts with diverse target mRNAs to regulate their abundance and translation in a wide range of contexts including the establishment of …

So There I Was, Jesse Marie Baggett

Graduate Theses, Dissertations, and Problem Reports (ETD)

This written thesis provides a description and analysis of my thesis exhibition, So There I Was, which presents a body of ceramic sculptures and paintings that explore themes of adventure, travel, and shared experiences. The work reimagines personal experiences through a cast of animal characters, with a rabbit acting as a stand-in for myself. These narratives are inspired by events from my own life and are transformed into imaginative scenes that emphasize playfulness, wonder, and storytelling.

The sculptures combine toy-like animal figures, pull carts, and miniature architectural structures to create playful environments that resemble playsets or staged scenes where …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Overcoming Radiation Resistance: Ferroptosis Induction To Sensitize Solid Tumors To Radiation Therapy, Joseph Carmicheal, Caden M. Fritson, Alexandra Seas, Heidi M. Vieira, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

Hu308, A Selective Cannabinoid Type-2 Receptor Agonist, Mitigates Sars-Cov-2 Spike Protein-Induced Acute Lung Injury In Mice, Janette Lockett, Gregory Nicholson, Nicholas Richards, Ryan Washington, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to pose major health challenges despite effective vaccination efforts. The sustained occurrence of breakthrough infections and emerging variants of the virus highlights the need for additional therapeutic strategies. Given the anti-inflammatory role of the cannabinoid type 2 receptor (CB2R), we examined the effect of CB2R activation in SARS-CoV-2 spike protein subunit 1 (S1SP)-induced acute lung injury (ALI).

Methods

ALI was induced in mice by intratracheal (i.t.) administration of S1SP, followed by treatment with the CB2R agonist HU308 (5 mg/kg, intraperitoneal: i.p.) 1 h …

Investigation Of A Global Mouse Methylome Atlas Reveals Subtype-Specific Copy Number Alterations In Pediatric Cancer Models., Melanie Schoof, Tuyu Zheng, Martin Sill, Roland Imle, Alessia Cais, Lea Altendorf, Alicia Fürst, Nina Hofmann, Kati Ernst, Dominik Vonficht, Kenneth Chun-Ho Chan, Tim Holland-Letz, Andreas Postlmayr, Ryo Shiraishi, Wanchen Wang, Alaide Morcavallo, Michael Spohn, Carolin Göbel, Judith Niesen, Levke-Sophie Peter, Franck Bourdeaut, Zhi-Yan Han, Yanxin Pei, Najiba Murad, Fredrik J. Swartling, Jessica Taylor, Monika Yadav, Garrett R. Gibson, Richard J. Gilbertson, Matthias Dottermusch, Rajanya Roy, Kornelius Kerl, Rainer Glass, Jiying Cheng, Martin A. Horstmann, Gerrit Wolters-Eisfeld, Haotian Zhao, Dominik Sturm, Viveka Nand Yadav, Louis Chesler, Simon Haas, William A. Weiss, Paul A. Northcott, Lena M. Kutscher, Ana Guerreiro Stucklin, Olivier Ayrault, Julia E. Neumann, Daisuke Kawauchi, David T W Jones, Kristian Pajtler, Ana Banito, Stefan M. Pfister, Ulrich Schüller, Marc Zuckermann

Manuscripts, Articles, Book Chapters and Other Papers

Copy number alterations (CNAs) are hallmarks of cancer, yet investigation of their oncogenic role has been hindered by technical limitations and missing model systems. Here we generated a genome-wide DNA methylation and CNA atlas of 106 genetic mouse models across 31 pediatric tumor types, including 18 new models for pediatric glioma. We demonstrated their epigenetic resemblance to human disease counterparts and identified entity-specific patterns of immune infiltration. We discovered that mouse tumors harbor highly recurrent CNA signatures that occur distinctly based on the tumor subgroup and driving oncogene and showed that these CNAs share syntenic regions with the matching human …

Rewiring The Immune Response In Lung Cancer: Current Progress In Bispecific Antibodies, Car-T Therapy, And The Rise Of In Vivo Car-T Platforms, Lei He, Yi Sun, Bowen Ma, Guojun Lang, Jianguo Wen, George R Blumenschein, Hong Ma

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality worldwide and continues to impose a major clinical burden, particularly in advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although targeted therapies, antiangiogenic agents, immune checkpoint inhibitors, and antibody-drug conjugates have improved outcomes in selected patients, durable responses remain limited by primary and acquired resistance. Here, we comprehensively review recent progress in immunologically oriented therapeutic strategies for lung cancer, focusing on bispecific antibodies, chimeric antigen receptor (CAR) T-cell therapy, and emerging in vivo CAR-engineering modalities. We further elaborate on the clinical rationale, latest translational and early clinical evidence, …

Peripheral Cd200r Signaling: A Critical Regulator Of Post-Stroke Inflammation In Aged Mice, Conelius Ngwa, Afzal Misrani, Yan Xu, Jingjing Wang, Rodney Ritzel, Fudong Liu

Faculty, Staff and Student Publications

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16-19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then …

Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning

Faculty, Staff and Student Publications

Recent breakthroughs in radiopharmaceutical (RP) therapy have emerged interest in employing Auger electron (AE)-emitting radionuclides as potential agents for precise theranostics. AE provides energy with exceptional localization due to their short tissue penetration range (TPR, < 10 nm), rendering them particularly effective for targeting nuclear DNA in tumor cells. In this context, AE-emitting radionuclide therapy (AE-emitting RLT) enables the targeted destruction of tumor cells while reducing harm to adjacent healthy tissue, a significant challenge in this field. Preclinical and early clinical investigations reveal the efficacy of AE-emitting RLTs in the theranostics of diverse malignancies, such as glioblastoma, prostate cancer, and neuroendocrine tumors. Notwithstanding these developments, challenges and limitations persist regarding dosimetry, delivery efficiency, and the treatment of radiotoxicity. A new paradigm is being developed to tackle the obstacles encountered by integrating molecular target markers (e.g., PARP) that function near the nucleus to improve the intranuclear delivery efficiency of AE-emitting radionuclides. Novel radiochemical methods such as these have facilitated the more stable and efficient labeling of biomolecules with AE-emitting radionuclides. Also, recent advances in DNA-molecular targeting, nanoparticles, nucleic acid/protein engineering, click- or bioorthogonal conjugation chemistry, and artificial intelligence (AI)-based structure modeling present concrete opportunities to overcome these limitations. Moreover, the integration of diagnostic imaging companion platforms employing theranostic radioisotope pairings facilitates real-time assessment of therapeutic efficacy and biodistribution, resulting in the formulation of enhanced treatment regimens. This review summarizes the prior development, recent advancements, barriers in clinical implementation, and future perspective of AE-emitting RLTs.