Digital Commons Network^™

Mechanism Of Anticancer Action Of Bifidobacterium: Insights From Gut Microbiota, Hoang Do, Esther Asiamah, Mayanijesu Olorife, Arathi Pillai, Sakshi Patel, Ponniah Selvakumar, Sidhartha D Ray, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Bifidobacterium has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that bifidobacterium can actively fight against various types of cancer, including those of the colon, lungs, breast, and stomach. Research indicates that several species of bifidobacterium can potentiate the action of chemotherapy, immunotherapy and radiation therapy in battling tumors, and reducing their adverse effects. Bifidobacteria shows its multipronged effect by modulating various immunomodulatory and inflammatory signaling pathways, potentially leading to the suppression of tumor growth. Moreover, different species of bifidobacteria are known to regulate signaling molecules …

How Life Enrichment Farms Promote Independence, Health, And Well-Being Through Vocational Skills And Sensory Processing Skills, Olivia Stanek

Honors Theses

There is limited knowledge about life enrichment farms and their role in supporting individuals with disabilities. This project aimed to highlight how occupational therapy can collaborate with these farm-based programs to promote independence, health, and well-being among younger adults with autism spectrum disorder and other developmental disabilities. An evidence-informed approach and qualitative research methods were used to explore this question, including a literature review and an interview with AACORN Farms, a life enrichment farm located in Michigan. Findings were further examined through occupational therapy activity analysis to identify the vocational, sensory, and meaningful engagement opportunities embedded within the various areas …

Effect Of Freezing And Freeze-Thaw Cycles On Equine Serum Insulin Concentration: A Pilot Study, Molly Wallace, Shea Porr, Lydia O'Sullivan

Honors College Theses

Insulin dysregulation is a key component of Equine Metabolic Syndrome (EMS), and is often a predisposing factor to conditions such as laminitis and hepatic lipidosis. Diagnosis of EMS is most often reached through a combination of glucose and insulin measurements in equine serum. Achieving an accurate result of insulin concentration is vital for diagnosis, making proper sample handling essential. The aim of this project was to evaluate the effect of repetitive freeze-thaw cycles on equine serum insulin concentrations. Serum was collected from 10 university-owned horses and split into four treatment groups: Unfrozen, Once Frozen, Twice Frozen, and Thrice Frozen. Unfrozen …

In-Silico Assessment Of Aortic Valve Function And Mechanics Under Hypertension, Jason A. Shar, Philippe Sucosky

Faculty Articles

Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder. While hypertension is a major risk factor, the mechanisms by which elevated blood pressure contributes to calcification are largely unknown. Given the established sensitivity of aortic valve (AV) tissue to mechanical cues, hypertension may subject AV leaflets to a stress state conducive to CAVD. To address this hypothesis, the objective of this study was to compare AV function and mechanics under normotensive (NTN, 120/ 80 mmHg), pre-hypertensive (preHTN, 125/80 mmHg) and hypertensive (HTN, 130/90 mmHg) conditions using fluid-structure interaction modeling.

Methods: AV flow and leaflet dynamics were …

Oligomeric Cystatin C Supports The Immunosuppressive Activity Of Myeloid Cells Through Interaction With Inhibitory Receptors, Chengcheng Zhang, Yubo He, Xiaoye Liu, Jingjing Xie, Meng Fang, Xing Yang, Ryan Huang, Qi Lou, Bufan Li, Ankit Gupta, Cheryl Lewis, Marc I Diamond, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Amyloid proteins are linked to various diseases; however, their functional roles in immunity and cancer remain unclear. Here, we establish a direct link between oligomeric cystatin C-a cysteine cathepsin inhibitor and a well-characterized amyloidogenic protein-within the tumor microenvironment and the immune inhibitory receptors LILRB2 and LILRB5 on myeloid cells. We demonstrated that human LILRB2 and LILRB5, along with their murine counterpart PIRB, serve as functional receptors for cystatin C oligomers. Engagement of these inhibitory receptors by oligomeric cystatin C enhances the immunosuppressive activity of myeloid cells, leading to T-cell suppression and tumor progression. Deletion of the CST3 gene, which encodes …

A Role For Gut Mycobiome And Altered Fungal-Bacterial Interactions In Women With Endometriosis†, Chandni Talwar, Ashirbad Guria, Kristi Hoffman, Scott Biest, Patricia Jimenez, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Endometriosis is a gynecological pathology prevalent in reproductive age women in which the inner uterine wall (endometrium) grows outside as ectopic lesions. The inflammation resulting from these growing implants closely associates with disease severity, causing chronic pain and infertility. Emerging studies have found altered bacterial communities in endometriosis and a causal role for gut bacteria in endometriosis. However, the role of the gut mycobiome, i.e., the fungal component of the microbiome in endometriosis is a current knowledge gap that needs to be addressed. In this study, utilizing the stool samples from women with endometriosis, we found that the gut fungal …

Mta-Cooperative Prmt5 Inhibitors Are Efficacious In Mtap-Deleted Malignant Peripheral Nerve Sheath Tumor Models, Xiaochun Zhang, Dana C Borcherding, Yang Lyu, Guangfeng Wang, Kevin He, Gorkem Oztosun, Ishita Sachdeva, Liuzhan Yang, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with poor prognosis. The enzyme methylthioadenosine phosphorylase (MTAP) is lost in ∼25% to 50% of MPNSTs, which is associated with loss of the tumor suppressor gene CDKN2A. Inhibition of PRMT5 was found to be synthetically lethal in cells with MTAP loss due to accumulation of the substrate methylthioadenosine (MTA), an endogenous PRMT5 inhibitor. TNG908 and TNG462 are clinical-stage MTA-cooperative PRMT5 inhibitors that demonstrate selectivity for MTAP-deleted (null) cells over MTAP-proficient [wild-type (WT)] cells. Both compounds drive durable tumor regressions in various cancer xenograft models with MTAP loss.

EXPERIMENTAL DESIGN: …

Rabies Virus-Vectored Lyme Disease Vaccine Provides Long-Term Protection Against Tick-Transmitted Borrelia Burgdorferi, Shantel Rios, Bibek Bhattachan, Christoph Wirblich, Anisha Chandwani, Kruthi Vavilikolanu, Jacob F. Myers, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. …

Developing A General Ai Model For Integrating Diverse Genomic Modalities And Comprehensive Genomic Knowledge, Zhenhao Zhang, Xinyu Bao, Linghua Jiang, Xin Luo, Zheyu Zhang, Jing Yin, Meiqi Zhao, Yichun Wang, Annelise Comai, Joerg Waldhaus, Anders S Hansen, Wenbo Li, Jie Liu

Faculty, Staff and Student Publications

Advances in next-generation sequencing technologies have vastly expanded the availability of diverse genomic, epigenomic, and transcriptomic data, presenting the opportunity to develop a general AI model that integrates comprehensive genomic knowledge into a unified model. Unlike previous predictive models, which are typically specialized to certain tasks, our general AI model unifies a wide range of genomic modalities, such as nascent RNA and ultra-high-resolution chromatin organization, within a multi-task architecture. Using ATAC-seq and DNA sequences as inputs, we incorporated diverse genomic modalities as output, and the model exhibits strong generalizability across different cell types and tissues in all tasks we trained. …

The Unfolded Protein Response-Novel Mechanisms, Challenges, And Key Considerations For Therapeutic Intervention, P M Quan Mai, Tam-Anh Truong, Sai Kumar Samala, Bhoomika Muruvekere Lakshmisha, Prapannajeet Biswal, Khadijeh Koushki, Prudhvi Chand Mallepaddi, Geraldine Vijay, Sunil Krishnan

Faculty, Staff and Student Publications

Background: The unfolded protein response (UPR) is an evolutionarily conserved, synchronized, and orchestrated process triggered by eukaryotic cells in response to endoplasmic reticulum (ER) stress. UPR restores the ER's capacity to handle large protein loads within it, and still fold and process these proteins accurately. Many recent studies have documented the non-canonical roles of the UPR, outside of protein quality control, in the context of lipid metabolism and the immune system in cancer. Cancer cells have been known to hijack the UPR to promote survival and evade immune surveillance. However, the underlying mechanisms remain poorly understood.

Objectives: Here, we critically …

Design, Optimization, And Development Of Ripk1 Degraders With Improved Pharmacokinetic And Pharmacodynamic Properties, Dong Lu, Xin Yu, Hanfeng Lin, Ran Cheng, Bin Yang, Min Zhang, Jingjing Chen, Feng Li, Xiaoli Qi, Jin Wang

Faculty, Staff and Students Publications

Pharmacological degradation of receptor-interacting protein kinase 1 (RIPK1) offers a compelling therapeutic strategy to overcome its scaffolding role in tumor resistance and to enhance the efficacy of immune checkpoint blockade (ICB) therapies. In this study, we report the discovery of a novel RIPK1 degrader, LD5097(24b), developed through systematic optimization of its precursor compound, LD4172—specifically refining the linker, RIPK1 warhead exit vector, and VHL ligand components. LD5097(24b) exhibits potent and selective RIPK1 degradation, triggering rapid and efficient downregulation of RIPK1 and significantly enhancing TNFα-mediated apoptosis in Jurkat cells. Compared to LD4172, LD5097(24b) demonstrates markedly improved metabolic stability and pharmacokinetic properties. In …

Genetic And Embryonic Transcriptome Analyses Reveal The Molecular And Developmental Basis Of Mayer-Rokitansky-Küster-Hauser Syndrome, Na Chen, Xi Cheng, Sen Zhao, Hengqiang Zhao, Chenglu Qin, Yaru Zhang, Xijuan Lin, Qing Li, Yuan Wang, Jia Kang, Jing Yu, Jianbin Guo, Qianqian Gao, Jiali Duan, Yuchen Niu, Jianzhong Su, Zhihong Wu, Terry Jianguo Zhang, Wanlu Liu, Pengfei Liu, Shan Deng, Nan Wu, Lan Zhu

Faculty, Staff and Students Publications

Background: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterised by aplasia of the uterus, cervix and upper part of the vagina. The genetic aetiology remains incompletely understood.

Methods: We performed gene-level and gene set-level burden analyses based on exome sequencing/genome sequencing data from 727 probands with MRKHS and 2504 female control individuals. Single-cell RNA sequencing (scRNA-seq) was performed on human and mouse embryonic metanephros at different developmental stages. Genetic and transcriptomic data were integrated to prioritise suboptimal genetic signals, identify relevant cell types and determine key developmental stages. Potential digenic inheritance was assessed and prioritised using coexpression patterns from scRNA-seq data.

Results: We …

Targeting Tomm40 And Tomm22 To Rescue Statin-Impaired Mitochondrial Function, Dynamics, And Mitophagy In Skeletal Myotubes, Neil V Yang, Sean Rogers, Rachel Guerra, Justin Y Chao, David J Pagliarini, Elizabeth Theusch, Ronald M Krauss

2020-Current year OA Pubs

Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well-tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated in the development of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates the transcription of

Lair1 Prevents Excess Inflammatory Tissue Damage In Staphylococcus Aureus Skin Infection And Cutaneous T-Cell Lymphoma, Hannah K. Dorando, Evan C. Mutic, Kelly L. Tomaszewski, Yulia Korshunova, Ling Tian, Mellisa K. Stefanov, Chaz C. Quinn, Deborah J. Veis, Juliane Bubeck Wardenburg, Amy C. Musiek, Neha Mehta-Shah, Jacqueline E. Payton

2020-Current year OA Pubs

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the underlying mechanisms remain unclear. We have previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice lack a LAIR2 homolog, so we used Lair1 knock-out (KO) mice to model LAIR2 overexpression. In a model of S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT despite similar bacterial burdens. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile …

Reliability And Validity Of A Modified Version Of The Consumer Assessment Of Healthcare Providers And Systems (Cahps®) Clinician And Group Visit Survey 4.0 (Beta) For Ambulatory Behavioral Health Care, Jessica K. Jeffrey, Ron D. Hays, Randi Hissom, Mark Grossman, Samuel A. Skootsky

Patient Experience Journal

Patient experience is a fundamental indicator of healthcare quality. A patient experience survey that assesses telemedicine and in-person ambulatory behavioral health care is needed. This study aims to adapt the CAHPS Clinician and Group Visit Survey 4.0 (beta) to assess adult patient experience with ambulatory behavioral health services and its reliability and validity. Seven behavioral health subject matter experts (psychiatrists, therapists with master’s degrees, and primary care physicians) at an integrated delivery system aligned with an academic institution provided input to select a subset of items and make minor wording adjustments to the CAHPS survey. The adapted survey was administered …

Enhancing System-Level Quality Improvement Through Patient-Inclusive Teamwork: A Review, Shaik Mohiuddin

Patient Experience Journal

Engaging patients in quality improvement (QI) initiatives offers significant advantages, including increased patient satisfaction, improved outcomes, and the integration of creative insights from patient perspectives. This review synthesizes findings from 14 peer-reviewed articles retrieved from PubMed and Google Scholar, focusing on patient-inclusive teamwork in healthcare settings. Despite the recognized benefits, patient involvement remains limited due to cultural and professional barriers, logistical challenges, and the need for structured training programs. The review contrasts conventional provider-centered approaches with patient-centered models, emphasizing the importance of policy reform, organizational culture change, and supportive training to enhance patient engagement. Traditional QI strategies often overlook patient …

“Better Than Any Medicine:” Understanding How Therapy Dogs Support Patients Presenting With Mental Health And Substance Use Concerns In An Emergency Department Setting, Alexandria R. Pavelich, Colleen A. Dell, James Stempien, Holly Mckenzie, Aimee Hozack, Jane Smith, Alexis Rowsell, Janet Gunderson, Elizabeth Pease

Patient Experience Journal

In Canada, emergency departments have a large number of patients with mental health and substance use concerns passing through their doors. Our research aim was to assess the impact that therapy dog visits may have for patients presenting with mental health and/or substance use concerns to an emergency department based in Saskatoon, Saskatchewan. Working alongside an active patient advisory group and community-based therapy dog program volunteers, our mixed method approach utilizing ethnography, surveys, and interviews showed that therapy dog visitation had a beneficial impact on both patients and staff, thus improving the overall patient experience. Our study displays how the …

Impact Of Non-Pharmacological Interventions On Patient Experience, Opioid Use, And Healthcare Utilization In Adult Cardiac Surgery: A Randomized Controlled Mixed Methods Trial, Julie R. Piazza, Alexander A. Brescia, Jessica N. Jenkins, Alexander J. Ivacko, Xiaoting Wu, Sara M. Jafri, Christopher J. Varlamos, James C. Piazza, Lindsay K. Heering, Stefanie L. Peters, Molly Dwyer-White, Bailey H. Brown, Faraz N. Longi, Katelyn P. Monaghan, Frederick W. Bauer, Varun G. Kathawate, Melissa C. Webster, Amanda M. Kasperek, Nickole L. Garvey, Claudia Schwenzer, Kiran H. Lagisetty, Michelle Riba, Donald S. Likosky, Jennifer F. Waljee, Nicholas H. Osborne, Mary E. Byrnes, G. Michael Deeb

Patient Experience Journal

Non-pharmacological techniques designed to reduce anxiety, pain, and healthcare utilization have shown effectiveness in pediatric and non-surgical adult populations; however, their application has not been widely evaluated among adult surgical patients. This study randomized opioid-naive adults undergoing first-time, elective cardiac surgery to receive either targeted interventions from a trained “comfort coach” or usual care. The primary outcome assessed was healthcare utilization, specifically measured as the number of days at home within the first 30 days post-surgery. Secondary outcomes included postoperative opioid use and patient-reported outcomes, collected via validated surveys. Additionally, 50 participants in the intervention group completed semi-structured qualitative interviews …

Cv: Christina Jeslis (Nursing), Christina Jeslis

Nursing Department Faculty Curricula Vitae

No abstract provided.

Exploring The Vitronectin Binding Affinity And Cell Viability Effect Of Small Molecule Metabolites From Medicinal Plants For Neuroblastoma, Stephenie C. A Alaribe, Sofia Granados-Aparici, Akolade R. Oladipupo, Isaac Vieco-Marti, Blessing E. Titilayo, Gordon Allen, Rosa Noguera

Pharmaceutical Sciences and Research

High-risk neuroblastoma (HR-NB) is an aggressive form of childhood cancer with a five-year survival rate of less than 50%, underscoring the need for more efficacious and less toxic treatments. The glycoprotein vitronectin (VN) has been linked to poor prognosis in patients with HR-NB, thus inhibitors of VN function represent a promising avenue for molecular mechanotherapy. This study investigated the binding affinity between the somatomedin B (SMB) domain of VN and natural compounds from the medicinal plant, Olax subscorpioidea, targeting the plasminogen activator inhibitor-1 (PAI-1). The therapeutic potential of α-amyrin (AMY), lupeol (LUP), and olax chalcone A (olax CHA) was tested …

Systematic And Scoping Reviews: What They Are, Why They Matter, And How To Do Them Right, Sharon Duffy Mlis, Rowan Marye Mlis, Lsu Health Libraries

Library Instruction

Curious about evidence synthesis? This session offers a practical introduction to literature reviews and explains their role in evidence-based scholarship. You’ll learn the types of research questions they address and the structured six-step process for conducting them effectively. Recorded session from the information session that took place on November 12, 2025.

The Gut Microbiome As A Modulator Of Traumatic Brain Injury Pathology And Symptoms, Cole Vonder Haar, Marta Celorrio, Kris M Martens, Stuart H Friess, Sonia Villapol, Randal J Urban, Richard Pyles, Richelle Mychasiuk, Dennis Simon, Amanda Dave

2020-Current year OA Pubs

Traumatic brain injuries (TBIs) affect millions annually, leading to devastating neurobehavioral consequences and increasing risk for neurodegenerative and psychiatric diseases. However, therapies are lacking. Starting in 2018, dysbiosis of the gut microbiome was identified as an acute, and potentially chronic, pathology originating from TBI. Recent studies established that the microbiome contributes to the evolution of TBI pathology and functional impairments. The gut microbiome is the collection of microorganisms that inhabit the stomach through colon and is indicated as a contributor to myriad neurological and psychiatric conditions. This makes it an intriguing target to understand in the context of TBI. Thus, …

Low Mutation Rate But High Male-Bias In The Germline Of A Short-Lived Opossum, Yadira Peña-García, Richard J Wang, Muthuswamy Raveendran, R Alan Harris, Paul B Samollow, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but the mechanisms underlying these factors are still unclear. One approach to distinguishing between alternative mechanisms is to study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns of mutation in these organisms. Here, we study the germline mutation rate in the gray short-tailed opossum, Monodelphis domestica, a laboratory model species that becomes reproductively mature at less than 6 mo of age. Whole-genome sequencing of 22 trios reveals one of the lowest mutation rates per generation …

Slc35g3 Is A Udp-N-Acetylglucosamine Transporter For Sperm Glycoprotein Formation And Underpins Male Fertility In Mice, Daisuke Mashiko, Shingo Tonai, Haruhiko Miyata, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter …

Host Cysteine Proteases Promote The Severity Of Catheter-Associated Urinary Tract Infection And Kidney Fibrosis, Wei Xu, Jian Chen, Lisa K Mclellan, Ana L Flores-Mireles, David A Hunstad, Michael G Caparon

2020-Current year OA Pubs

UNLABELLED: The bacterium

IMPORTANCE: Catheter-associated urinary tract infections (CAUTIs) are the most prevalent healthcare-associated infection globally, with

Cardiac Sr-Mitochondria Contacts-Impact On Cardiac Physiology And Mitochondrial Fitness, Celia Fernandez-Sanz, Shey-Shing Sheu, Sergio De La Fuente

Center for Translational Medicine Faculty Papers

In adult cardiomyocytes, within the Mitochondrial Associated Membranes (MAMs), the sarcoplasmic reticulum (SR) and mitochondria juxtapose each other, forming a unique and highly repetitive functional structure throughout the cells. These SR-mitochondria contact sites have emerged as critical structures that regulate various physiological processes, including lipid exchange, calcium (Ca²⁺) communication, control of excitation-contraction bioenergetics coupling, and reactive oxygen species (ROS) production. Over the years, several scientific studies have reported the accumulation of diverse proteins within these SR-mitochondria close contacts. Some proteins strategically accumulate in these areas to enhance their function, such as the mitochondrial Ca²⁺ uniporter, while others …

Epigenetic Landscape In Lysosomal Storage Disorders: Mechanisms And Modulation, Andrés Felipe Leal, Harry Pachajoa, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Lysosomal storage disorders (LSDs) are rare substrate-accumulating diseases primarily characterized by mutations in genes encoding proteins involved in lysosomal function, most of which have enzymatic activity. Resulting lysosomal dysfunction leads to the overaccumulation of non- or partially degraded substrates. While it is true that enzyme deficiency is the primary cause of LSDs, the epigenetic alterations in DNA methylation, miRNA expression, and histone modifications appear to be critical mechanisms involved in the pathogenesis of LSDs. As epigenetic marks are, in most cases, reversible, their study becomes vital to developing strategies aimed at reversing epigenome alterations. Although classical therapeutic alternatives aim to …

Reprogramming Tumor Microenvironment Via Systemic Delivery Of Tlr3 Agonist And Manganese Nanoparticle, Young Seok Cho, Xingwu Zhou, Xiaoqi Sun, Ziye Wan, Julia Crowther, Mariko Takahashi, Swetha Kodamasimham, Qi Wu, May Thazin Phoo, Youngseo Na, Kai Han, Zaiye Li, Anna Schwendeman, Steven P Schwendeman, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Toll-like receptor (TLR) agonists, as potent immunostimulatory adjuvants, play a critical role in linking the innate and adaptive immune responses. However, their antitumor effects as cancer immunotherapeutic agents have been limited. Here, we report our finding that manganese ion (Mn2+) potentiates various TLR agonists, leading to robust activation of the TLR pathway and the stimulator of interferon genes (STING) pathway among innate immune cells. In particular, we have observed robust antitumor efficacy after intratumoral administration of a TLR3 agonist and Mn2+. To achieve systemic codelivery of TLR3 agonist and Mn2+, we have developed a low-molecular-weight poly(inosinic:cytidylic acid)-Mn2+ coordination lipid nanoparticle …

Hepatic Ischemia-Reperfusion Injury: Underlying Mechanisms And Concepts In Liver Surgery And Liver Transplantation, Jie Zhao, Lidan Hou, Kenneth J Dery, Xiaoyi Yuan, Kang Ho Kim, Jerzy W Kupiec-Weglinski, David R Hall, Caitlin J Thornley, Mark J Hobeika, Holger K Eltzschig, Cynthia Ju

Faculty, Staff and Student Publications

Hepatic ischemia-reperfusion injury (H-IRI) is a critical complication in liver surgery and liver transplantation, contributing to graft dysfunction and poor clinical outcomes. When hepatocyte protective mechanisms are insufficient to counteract energy depletion and oxidative stress during ischemia, cell death occurs. Tissue damage during H-IRI leads to the release of damage-associated molecular patterns (DAMPs), which recruit and activate immune cells such as neutrophils and monocytes, orchestrating the initiation, progression, and eventual resolution of sterile inflammation. Extended criteria donor (ECD) livers, particularly steatotic ones, are more vulnerable to H-IRI, leading to poorer outcomes and limiting expansion of the donor pool. However, the …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …