Digital Commons Network^™

Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 …

Differential Microbial Community Assembly Following Co-Housing Versus Microbiota Transplant, James S Weagley, Luis Alberto Chica Cárdenas, Ana Romani, Meagan E Sullender, Somya Aggarwal, Heyde Makimaa, Michael P Hogarty, Rachel Rodgers, Elizabeth A Kennedy, Lynne Foster, Lawrence A Schriefer, Megan T Baldridge

2020-Current year OA Pubs

Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transfer of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of faecal or caecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, faecal transplantation, and caecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which …

N-Linked Fucosylated Glycans Are Biomarkers For Prostate Cancer With A Neuroendocrine And Metastatic Phenotype, Joseph E Ippolito, Hani Nakhoul, Cody Weimholt, Elena Nunez, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at the time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of …

Two-Hit Mouse Model Of Heart Failure With Preserved Ejection Fraction Combining Diet-Induced Obesity And Renin-Mediated Hypertension, Justin H Berger, Xian Chen, Attila Kovacs, Et Al.

2020-Current year OA Pubs

Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We developed a novel "two-hit" model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF. C57Bl6/NJ mice fed a high-fat diet (HFD) for > 10 weeks were administered an AAV8-driven vector resulting in constitutive overexpression of mouse Renin1d. HFD-Renin (aka "HFpEF") mice demonstrated obesity and insulin resistance, moderate left ventricular hypertrophy, preserved systolic function, and diastolic dysfunction indicated …

T Helper 2 Cell-Directed Immunotherapy Eliminates Precancerous Skin Lesions, Tomonori Oka, Neel S. Raval, Mary Tabacchi, Lynn A. Cornelius, Et Al.

2020-Current year OA Pubs

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear. Herein, we demonstrate that calcipotriol-plus-5-FU immunotherapy induces T helper type 2 (Th2) immunity, eliminating premalignant keratinocytes in humans. CD4+ Th2 cells were required and were sufficient downstream of thymic stromal lymphopoietin cytokine induction by calcipotriol to suppress skin cancer development. Th2-associated cytokines induced IL-24 expression in cancer cells, resulting in toxic autophagy and anoikis followed by apoptosis. Calcipotriol-plus-5-FU immunotherapy was dependent …

Lung-Delivered Il-10 Mitigates Lung Inflammation Induced By Repeated Endotoxin Exposures In Male Mice, Aaron Schwab, Todd A. Wyatt, Oliver Schanze, Amy J. Nelson, Angela Gleason, Michael J. Duryee, Deanna Mosley, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of resolving inflammatory lung disease resulting from high-consequence occupational/environmental hazards are lacking. This study seeks to determine the therapeutic potential of direct lung-delivered interleukin (IL)-10 following repeated lipopolysaccharide exposures. C57BL/6 mice were intratracheally instilled with LPS (10 μg) and treated with IL-10 (1 μg) or vehicle control for 3 days. Lung cell infiltrates were enumerated by flow cytometry. Lung sections were stained for myeloperoxidase (MPO), CCR2, vimentin, and post-translational protein citrullination (CIT) and malondialdehyde-acetaldehyde (MAA) modifications. Lung function testing and longitudinal in vivo micro-CT imaging were performed. Whole lungs were profiled using bulk RNA sequencing. IL-10 treatment reduced …

Lung Disease In Relation To Unique Monocyte-Macrophage Subpopulations Induced By Combined Inhalant Endotoxin And Collagen-Induced Arthritis, Jill A. Poole, Aaron Schwab, Geoffrey M. Thiele, Todd A. Wyatt, Amy J. Nelson, Oliver Schanze, Angela Gleason, Michael J. Duryee, Bryant England, Ted R. Mikuls

Journal Articles: Environmental, Agricultural & Occupational Health

BACKGROUND: Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA), a model that recapitulates features of RA-associated interstitial lung disease (RA-ILD). As patients with RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize lung infiltrating monocytes/macrophages in a mouse model of RA-ILD and determine whether reducing these cells mitigates the development of lung disease.

METHODS: Autoimmune-prone DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for up to 5 weeks and CIA induction. …

The Cdk8 Kinase Module: A Novel Player In The Transcription Of Translation Initiation And Ribosomal Genes, Brittany Friedson, Stephen D Willis, Natalia Shcherbik, Alicia N Campbell, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Survival following stress is dependent upon reprogramming transcription and translation. Communication between these programs following stress is critical for adaptation but is not clearly understood. The Cdk8 kinase module (CKM) of the Mediator complex modulates the transcriptional response to various stresses. Its involvement in regulating translational machinery has yet to be elucidated, highlighting an existing gap in knowledge. Here, we report that the CKM positively regulates a subset of ribosomal protein (RP) and translation initiation factor (TIF)-encoding genes under physiological conditions in Saccharomyces cerevisiae. In mouse embryonic fibroblasts and HCT116 cells, the CKM regulates unique sets of RP and TIF …

Interferon-Gamma Receptor Signaling Regulates Innate Immunity During Staphylococcus Aureus Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Rachel W. Fallet, Tammy Kielian

Journal Articles: Pathology and Microbiology

A craniotomy is a neurosurgical procedure performed to access the intracranial space. In 3-5% of cases, infections can develop, most caused by Staphylococcus aureus biofilm formation on the skull surface. Medical management of this infection is difficult, as biofilm properties confer immune and antimicrobial recalcitrance to the infection and necessitate additional surgical procedures. Furthermore, treatment failure rates can be appreciably high. These factors, compounded with rapidly expanding rates of antimicrobial resistance, highlight the need to develop alternative treatment strategies to target and reverse the immune dysfunction that occurs during biofilm infection. Our recent work has identified CD4+ Th1 and Th17 …

Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed …

Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot

Journal Articles: Pathology and Microbiology

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a …

Extracellular Adherence Proteins Reduce Matrix Porosity And Enhance Staphylococcus Aureus Biofilm Survival During Prosthetic Joint Infection, Mohini Bhattacharya, Tyler D. Scherr, Jessica Lister, Tammy Kielian, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Biofilms are a cause of chronic, non-healing infections. Staphylococcus aureus is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of S. aureus biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap …

Effect Of Praziquantel Treatment On The Nutritional Status Of Children Infected With Schistosoma Haematobium, Louis Fok, Hongying Dai, David Brett-Major, Abebe Animut, Berhanu Erko, John Linville, Yohannes Negash, Abraham Degarege

Journal Articles: Epidemiology

This quasi-experimental trial examined the relationship between Schistosoma haematobium infection and nutritional status, and the impact of single dose praziquantel (PZQ) therapy on undernutrition. A total of 353 children were examined, 112 of which were infected with S. haematobium and treated with PZQ. Children's heights, weights, and mid-upper arm circumferences (MUAC) were measured at baseline and one month post-treatment. Infected children had significantly smaller mean BMI-for-age z-scores (BAZ) (-1.16 vs. 0.11, p < 0.01) and weight-for-age z-scores (WAZ) (-0.61 vs. -0.31, p = 0.03) than the uninfected ones at baseline. S. haematobium infection was associated with underweight (adjusted OR: 1.76, 95% CI: 1.63-1.90). One month after treatment, BAZ, WAZ, …

Zinc Promotes Mitochondrial Health Through Pgc-1alpha Enhancing Bacterial Clearance In Macrophages Infected With Mycobacterium Avium Complex, Ruxana Sadikot, Prabagaran Narayanasamy, Zhihong Yuan, Deandra R. Smith, Daren L. Knoell

Journal Articles: Pulmonary & Critical Care Med

Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn …

Change Through Social Media: Sparking Wildlife Conservation One Click At A Time, Bryce J. Fable, Lauren Fitzsimmons, Noshi Kapoor, Anne Reichle, Sara Wise, Robin O'Meallie, Greg Zboch

High Impact Practices Student Showcase Fall 2025

As the natural world faces unprecedented threats, conservation efforts depend not only on research and policy but also on public awareness and engagement. This project partnered with the Zoo Miami Foundation to promote awareness through social media initiatives and interactive educational events at the University of Central Florida.

The authors began by studying Zoo Miami’s ongoing conservation projects and the specific environmental pressures faced by endangered species and habitats. To align with Zoo Miami’s exceptional standard of credibility, the team conducted in-depth research that extended beyond the foundation’s website to create material that served to both inform the general public …

Eyes And The Impossible (2023) By David Eggers, Peter Shea

Middle Grades Books

The Eyes and the Impossible joins the genre of talking animal stories, deepening that genre, suggesting new ways that the animal point of view could help humans understand their strivings for limitlessness and their temptations to retreat into a safe world. The dog narrator, Johannes and his animal friends and colleagues are all open to the world beyond their cozy home; they are willing to take great risks to learn something new. The book models the adventure of learning and growing up, without sacrificing the power of a great story.

Spleen And Peripheral Blood Immunopathology In An Outbred Model Of Adult-Stage Murine Schistosomiasis, Thomas Schulze, Andrew J. Neville, Evie G. Ehrhorn, Sarah A. Alsuleiman, Jonathan L. Vennerstrom, Paul H. Davis

Journal Articles: Pharmaceutical Sciences

Schistosomiasis, a parasitic disease caused by flatworms of genus Schistosoma, is a neglected tropical disease that causes significant morbidity in the developing world. Despite numerous efforts to eradicate the disease, the parasite remains a significant global burden, particularly within Sub-Saharan Africa. Schistosoma species possess an arsenal of potent mechanisms to defend against direct attack from host immune cells and a remarkable ability to modulate the host immune system through proximal and systemic modes that facilitate its stage-specific development, survival, and reproduction. Standardized animal models have been developed that serve as an important resource for dissecting parasite and host immunobiology …

Targeted Deletion Of Cxcl1 In Mscs Regulates Osteogenesis And Suppresses Bone-Metastatic Prostate Cancer, Catherine S. Johnson, Diane L. Costanzo-Garvey, Julio C. Valencia, Sanjana Rajgopal, Theodore Reed, Emma R. Brannon, Jeremy S. Frieling, Deanna Mosley, Todd A. Wyatt, Elijah F. Edmondson, Kabhilan Mohan, Grinu Mathew, Leah M. Cook

Journal Articles: Environmental, Agricultural & Occupational Health

Bone metastasis continues to be the greatest challenge in treating patients with prostate cancer despite ongoing research. In bone, prostate cancer tumors hijack normal bone remodeling processes to drive cancer progression. However, it is unclear how these interactions drive bone-metastatic prostate cancer growth in the bone environment. To understand the mechanisms associated with bone-metastatic prostate cancer regulation of mesenchymal stem cells (MSC), we previously identified that bone-metastatic prostate cancer induces MSC expression of the pro-inflammatory chemokine CXCL8 and its mouse functional homologue Cxcl1. To date, there has been little to no information about the role of CXCL1/8 in MSC biology …

Harnessing The Human Gut Microbiota: An Emerging Frontier In Combatting Multidrug-Resistant Bacteria., Wenwen Ding, Yiwen Cheng, Xia Liu, Zhangcheng Zhu, Lingbin Wu, Jie Gao, Wenhui Lei, Yating Li, Xin Zhou, Jian Wu, Yongtao Gao, Zongxin Ling, Ruilai Jiang

Faculty Research 2025

Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight …

Marmosets As Model Systems For The Study Of Alzheimer's Disease And Related Dementias: Substantiation Of Physiological Tau 3r And 4r Isoform Expression And Phosphorylation., Hasi Huhe, Sarah M Shapley, Duc M Duong, Fang Wu, Seung-Kwon Ha, Sang-Ho Choi, Julia Kofler, Yongshan Mou, Thais Rafael Guimaraes, Amantha Thathiah, Caroline M Watson, Lauren K H Schaeffer, Gregory W. Carter, Nicholas T Seyfried, Afonso C Silva, Stacey J Sukoff Rizzo

Faculty Research 2025

INTRODUCTION: Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied.

METHODS: Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.

RESULTS: 3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. Mass spectrometry analysis revealed that tau peptides in marmoset corresponded to the 3R and 4R peptides in human brain, with 3R predominating at birth and an ≈40%:60% 3R:4R ratios in adolescents and adults; tau was distributed widely in neurons, with localization …

Comprehensive Single-Cell Aging Atlas Of Healthy Mammary Tissues Reveals Shared Epigenomic And Transcriptomic Signatures Of Aging And Cancer., Brittany Lynn Angarola, Siddhartha Sharma, Neerja Katiyar, Hyeon Gu Kang, Djamel Nehar-Belaid, Sunghee Park, Rachel Gott, Giray N Eryilmaz, Mark A Labarge, Karolina Palucka, Jeffrey Chuang, Ron Korstanje, Duygu Ucar, Olga Anczuków

Faculty Research 2025

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk⁺, memory CD4⁺, γδ) and M2-like macrophages expand with age. …

Rapid Changes In Plasma Corticosterone And Medial Amygdala Transcriptome Profiles During Social Status Change Reveal Molecular Pathways Associated With A Major Life History Transition In Mouse Dominance Hierarchies., Tyler M Milewski, Won Lee, Rebecca L Young, Hans A Hofmann, James P Curley

Faculty Research 2025

Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, males that were socially dominant prior to being placed into new social hierarchies exhibit higher increases in plasma …

Single-Cell And Bulk Transcriptional Profiling Of Mouse Ovaries Reveals Novel Genes And Pathways Associated With Dna Damage Response In Oocytes., Monique Mills, Chihiro Emori, Parveen Kumar, Zachary Boucher, Joshy George, Ewelina Bolcun-Filas

Faculty Research 2025

Immature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response (DDR) in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53, and TAp63, regulate primordial follicle elimination in response to DNA damage. However, the mechanism leading to their demise is still poorly characterized. Single-cell and bulk RNA sequencing were used to determine the DDR in wild-type and Chek2-deficient ovaries. A low but oocyte-lethal dose of ionizing radiation induces ovarian DDR …

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas

Bioelectrics Publications

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, …

The Ptp4a3 Inhibitor Kvx-053 Reduces Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Virulence, Inflammation, And Development Of Acute Lung Injury In K18-Hace2 Mice, Ruben M. L. Colunga-Biancatelli, Pavel A. Solopov, Caitlin M. Woodson, Irving Coy Allen, Ivan Akhrymuk, Maryna Akhrymuk, Brittany N. Heath, Hannah M. Ivester, Tierney Day, Dan E. Austin, Kylene Kehn-Hall, John S. Lazo, Elizabeth R. Sharlow, John D. Catravas

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global health crisis, marked by high transmissibility and virulence. Despite widespread vaccination efforts, effective treatments for COVID-19, particularly for severe cases leading to Acute Respiratory Distress Syndrome (ARDS), remain limited. This study investigates the efficacy of KVX-053, a protein tyrosine phosphatase type IVA (PTP4A3) small molecule inhibitor, in modulating SARS-CoV-2-induced inflammation and lung injury using in vitro cell models and in vivo K18-hACE2 transgenic mice. KVX-053 reduced in vitro pro-inflammatory cytokine expression, including TNFα, CXCL10, and CXCL11, without impacting viral replication or cell viability. K18-hACE2 mice treated with KVX-053 demonstrated …

Perspective On Alcohol-Induced Organ Damage Via Autophagy-Dependent Cellular Changes, Ahmed Bakheet, Murugadas Anbazhagan, Shirish Barve, Srinivasan Dasarathy, John Dickinson, Wen-Xing Ding, Terrence Donohue, Thiyagarajan Gopal, Anna Gukovskaya, Kusum K. Kharbanda, John J. Lemasters, Natalia A. Osna, Pal Pacher, Lucy Sloan, Luis F. Vilches, Viswanathan Saraswathi, Xiao-Ming Yin, Zhi Zhong, Paul G. Thomes

Journal Articles: Internal Medicine

Alcohol-induced organ damage is a major global health concern and a leading cause of disability and mortality. In addition to the liver, chronic alcohol consumption adversely affects multiple organ systems, including the cardiovascular and neuromuscular systems, the gastrointestinal tract, adipose tissue, kidneys, pancreas, and the brain. Organ damage begins with necrosis (cell death) followed by tissue injury, which triggers immune responses aimed at tissue repair. However, with continued heavy drinking, these reparative responses transition into inflammatory responses which exacerbate tissue injury and accelerate disease progression. Macroautophagy, commonly referred to as autophagy, is a vital and evolutionarily-conserved digestive process in eukaryotic …

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …

Wasting Disease Of A Marine Foundation Species Links Community Interactions To Disease Dynamics, Lillian R. Aoki, Olivia J. Graham, Reyn M. Yoshioka, Rebecca Maher, Lindsay Alma, Eileen E. Hofmann, Colleen A. Burge, Drew Harvell, Maya L. Groner

CCPO Publications

Infectious disease plays a key role in shaping marine communities, including in seagrass meadows, which form biodiverse coastal habitats. Eelgrass (Zostera marina) is the most widespread seagrass species and is susceptible to seagrass wasting disease, caused by the protist Labyrinthula zosterae. As a foundation species, eelgrass strongly influences ecosystem structure, function and services; recent work has begun to explore the links between critical community interactions and seagrass wasting disease. Here, we highlight recent advances about how the eelgrass community regulates and responds to seagrass wasting disease, from the microbiome to herbivores and filter feeders. We further show …

Selective Nutrient Incorporation May Underestimate Heterotrophy Of A Mixotrophic Reef-Building Coral, Connor R. Love, Marleen Stuhr, Michael D. Fox, Veronica Z. Radice, Maoz Fine, Kelton W. Mcmahon, David L. Valentine

Biological Sciences Faculty Publications

Mixotrophic reef-building corals acquire nutrition via photosynthate translocation from endosymbiotic microalgae and by heterotrophic prey/particle capture. Heterotrophy promotes resistance to, and recovery from, environmental stress, but quantifying coral heterotrophy remains difficult due to complex resource exchanges within the coral holobiont. We interrogated the response of multiple biomarkers to coral heterotrophy using fatty acid profiling and stable isotope analysis of Stylophora pistillata grown along a controlled feeding gradient from pure autotrophy to pure heterotrophy. We found that fatty acids and nitrogen were effectively incorporated into both coral host and symbiont tissues, while carbon, which is the primary target for conventional heterotrophy …

Novel Insights Into Beta Cell Er Stress Chop And It's Role In Hfpef Development, Balaji Srinivas, Paula Fortuno, Hongmei Peng, Jiang Xu, Hamid Suhail, Hani N. Sabbah, Nour-Eddine Rhaleb, Khalid Matrougui

Department of Physiological Sciences Faculty Publications

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction and often associated with hypertension and metabolic disturbances. We aimed to determine the inter-relationship between C/EBP homologous protein (CHOP) in b-cells and HFpEF development.

Methods: Eight-week-old male mice b-cell^flox/flox and b-cell^CHOP-/- were randomly divided into four groups: control b-cell^flox/flox and b-cell^CHOP-/- mice subjected to standard diet and water. b -cell^flox/flox and b-cell^CHOP-/- mice fed a high-fat diet (HFD) and L-NAME (0.5 g/L) for five weeks. A comprehensive cardiovascular, metabolic, and histological evaluation was conducted.

Results: Following …