Chemicals and Drugs Commons^™

Computational Repurposing And Experimental Validation Of Ybx1 Inhibitors In Hepatocellular Carcinoma, Omar Karkoutly, Veerababu Nagati, Subhash Chauhan, Manish Tripathi

School of Medicine Publications

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. While early-stage HCC can often be treated with surgical resection, ablation, or liver transplantation, advanced disease typically relies on systemic chemotherapy. Sorafenib is the standard first-line therapy for advanced and unresectable HCC; however, both intrinsic and acquired resistance remain major clinical challenges. The Y-box binding protein-1 (YBX1), a transcription factor implicated in drug resistance across multiple cancers, is highly expressed in HCC and represents a potential therapeutic target. This study aimed to identify novel YBX1 inhibitors using a drug repurposing strategy to overcome sorafenib resistance. Methods: A …

Encapsulation Of Cannabidiol In Chitosan-Stabilized Argan Oil Nanoemulsion As A Potential Dermal Drug Delivery System For Psoriasis Treatment, Yousra Mdarhri, Vinicius De-Monte-Vidal, Camila De-Almeida-Perez-Pimenta, Selene Cuello-Rodríguez, Ahmed Touhami, Fakhita Touhami, Mohamed Chabbi, Victoria Díaz-Tomé

Physics & Astronomy Faculty Publications

Background: Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, exhibits therapeutic potential for various conditions, including inflammation, pain, and skin disorders, making it a promising candidate for the topical treatment of psoriasis. However, its poor water solubility and instability limit its therapeutic efficacy. This study focuses on the development and characterization of CBD-loaded nanoemulsions using argan oil as the lipid phase, with and without a chitosan coating, which serves as a stabilizing and functional biopolymer. Methods: Nanoemulsions (NE) and chitosan-stabilized nanoemulsions (CS-NE), both without CBD (serving as controls), and CBD-loaded variants (CBD-NE and CBD-CS-NE) were prepared and characterized for …

Microbiome-Responsive Hydrogels: From Biological Cues To Smart Biomaterials, Rajesh Vadlapatla, Amir Nasrolahi Shirazi, Ajoy Koomer, Judy Weng, Matthew Ernest Ghilarducci, Alai Qudus, Keykavous Parang

Pharmacy Faculty Articles and Research

Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect the dynamic, disease-relevant complexity of native tissue microenvironments. Microbe-colonized tissues display distinctive biochemical features driven, shaped by microbial metabolism, including localized pH gradients, short-chain fatty acid production, secretion of quorum-sensing molecules, biofilm formation, and expression of specialized enzymes. These endogenous, spatiotemporally regulated signals are closely linked to host physiology and pathology but remain underutilized in hydrogel …

Plasma Ca125 Levels As A Predictor Of Major Adverse Cardiac Events In Patients With Acute Coronary Syndrome: A Six-Month Follow-Up Study, Nazlı Dilek Çolak, Turgut Karabağ, Onuralp Çalışkan, Songül Tezcan

Journal of the Saudi Heart Association

Objectives: Carbohydrate antigen 125 (CA125) is associated with different cardiovascular conditions. This study aimed to determine CA125 levels in patients with acute coronary syndrome (ACS) and the potential relationship between major adverse cardiac events (MACE) in the short-term following.

Methods: This prospective cohort study was conducted in a coronary care unit between May and November 2022. Plasma CA125 levels were measured only once upon hospital admission. Patients were followed for six months. All-cause mortality, recurrent acute coronary syndrome, requirement for revascularization, decompensated heart failure, cardiogenic pulmonary edema, atrial fibrillation, and stroke were recorded as MACE.

Results: A total of 127 …

Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 inhibits synovial macrophage (SM) activation via xanthine oxidase (XO) and hypoxia inducible factor alpha (HIF-1α) suppression. We aimed to evaluate the contribution of PRG4-CD44 interaction to synovial homeostasis and investigate PRG4’s signaling dysfunction in synovial tissues from patients with osteoarthritis (OA). We hypothesized that CD44 mediates synovitis due to PRG4 loss and that PRG4 signaling dysfunction is associated with high-grade synovitis in OA.

Methods

Prg4^{FrtloxP/FrtloxP} are transgenic mice wherein tamoxifen (TAM) inactivates the Frt allele and creates a knockout state (Prg4^{FrtKO/FrtKO …}

Exploring The Theoretical Foundation With Rupture And Delayed Rupture Experiments, Shi-Qing Wang, Junpeng Wang, Asal Y. Siavoshani, Cheng Liang

University Research

We carry out uniaxial continuous and step stretching of various cross-linked polymer networks to demonstrate how characteristics of rupture during continuous stretching and delayed rupture after step stretching can be used to probe the structure of the emergent kinetic activation theory of bond dissociation (KATBD) for elastomeric failure. Based on delayed rupture experiments, we show that the network lifetime tntw, taken as the incubation time tdel-rupt for delayed rupture, depends on temperature in an Arrhenius like manner and is exponentially sensitive to the degree of network stretching (depicted by the step-stretch ratio λss). Rupture at λb during continuous stretching for …

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

Off-Label Use Of Tirzepatide To Reduce Alcohol And Nicotine Consumption: A Randomized Control Trial, Yvannia Gray, Benjamin Latey, Hayden Mcaffee, Karissa Mccown, Leon Boyles, Sanjana Pothuraju, Andrew Payne

Annual Research Symposium

No abstract provided.

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

Albumin-Binding Domains In Therapeutic Protein Engineering: A Structural And Computational Perspective On Rational Design, Matthew Argyle, Dallin M. Chipman, Anna Claire Woolley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

Therapeutic proteins face a critical pharmacokinetic challenge: rapid clearance from circulation limits their clinical efficacy. Albumin-binding domains (ABDs) offer an elegant solution by enabling therapeutic proteins to “hitchhike” on serum albumin’s favorable 19-day half-life through FcRn-mediated recycling. Clinical validation through approved therapeutics like ozoralizumab demonstrates the success of this approach, with preclinical studies showing fusion to an ABD extended half-life to 18 days. This review provides an analysis of ABD-fusion protein design, integrating structural biology, computational prediction, and rational engineering principles. We catalog the major classes of albumin-binding modalities, including bacterial three-helix bundle domains, engineered peptides, antibody-derived binders, and alternative …

Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez

Annual Research Symposium

No abstract provided.

Mutations Altering The Dna Binding Domains Of The Human Rad52 Protein Exert Distinct Effects On Homologous Recombination Repair In Saccharomyces Cerevisiae, Glenn M. Manthey, Elise W. Wolf, Jason Xu, M. Cristina Negritto, Renee A. Bouley, Ruben C. Petreaca, Adam M. Bailis

College of Health Professions Faculty Papers

RAD52 is a conserved member of the homologous recombination repair (HRR) apparatus from yeast to humans. Mutating conserved amino acids in the internal and external DNA binding domains of the human RAD52 protein (HsRAD52) has discrete effects in vitro. Previous studies have shown that HsRAD52 supports multiple mechanisms of HRR in budding yeast, suggesting the utility of this model system for exploring the correspondence between losses of HsRAD52 function in vitro and their impact in vivo. We report that disrupting the internal and external DNA binding domains of HsRAD52 produced distinct effects on the repair of genomic DNA double-strand breaks …

Rare Event: Neonatal Anaphylaxis Following Hepatitis B Vaccination – A Case Series From A Tertiary Care Center In India, Aarthi Ma, Revanth R

Advances in Clinical Medical Research and Healthcare Delivery

We report two cases of anaphylaxis following Hepatitis B vaccination in one-day-old neonates at a tertiary care hospital in India. Both cases presented with similar patterns of cutaneous reactions and respiratory symptoms shortly after intramuscular administration of the Hepatitis B vaccine. To our knowledge, this is among the few documented case series of neonatal anaphylaxis post–Hepatitis B vaccination, underscoring its rarity yet clinical importance. The cases highlight the critical importance of vigilant post-vaccination monitoring and prompt recognition of vaccine-associated adverse events in neonates. This report reviews current literature on anaphylaxis following vaccination and discusses optimal management strategies.

Engineering Enac Constructs To Examine Pip2 And Ubiquitin Competition On Enac Regulation And Stability, Lacie Johnson

Chemistry & Biochemistry Undergraduate Honors Theses

The epithelial sodium channel (ENaC) plays a critical role in sodium homeostasis, fluid balance, and blood pressure regulation. ENaC activity is tightly controlled by post-translational mechanisms, including ubiquitination-mediated degradation and phosphatidylinositol 4,5-bisphosphate (PIP2) dependent channel activation. PIP2 is a phospholipid necessary to facilitate the maximal channel opening. Previous studies suggest that intracellular PIP2 binding sites are located in proximity to ubiquitination sites on ENaC subunits, raising the possibility of PIP2 binding to influence channel stability and function. This thesis aimed to engineer and validate molecular tools capable of examining the interplay between PIP2 binding and ubiquitination in ENaC regulation. A …

Controlled Antibiotic Release From Emulsion-Loaded Alginate And Fibrin Hydrogels Using Ultrasound, Ziba Ghareh Nazi Fam, Asia Winslow, Mario Fabiilli, Sam Varghese, Brian Oeffinger, Flemming Forsberg, Noreen Hickok, Lauren Delaney

Department of Radiology Faculty Papers

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Vivek Kashyap, Neeraj Chauhan, Dae Joon Kim, Nirakar Sahoo, Tamer Oraby, Murali Yallapu, Subhash Chuahan, Bilal Hafeez

School of Medicine Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

February 2026, Swosu Rural Health Center

RURAL ROCKS

• Current Indications for Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
• CMS unveils LEAD, its new 10-year accountable care model
• UnitedHealthcare pauses effort to cut RPM coverage after stating the tech has 'no evidence'
• Walgreens unveils PharmStart to strengthen tech-to-pharmacist pipeline
• Rural Health Transformation Program awards announced—Here's who's getting the most in FY2026
• FDA Grants Two National Priority Vouchers
• 2026 Outlook: Hybrid care companies poised for growth driven by economic, policy tailwinds
• Brain Drain: Retail pharmacy struggles to retain pharmacists, pharmacy technicians
• The 5 biggest challenges facing retail pharmacy
• Retail pharmacy must mine the gaps
• CMS Establishes Office of Rural Health Transformation Nationwide …

Cancer Vaccine Targeting Mutated Gnaq-Expressing Uveal Melanoma, Vitali Alexeev, Mizue Terai, Sergei Koshkin, Olga Igoucheva, Takami Sato

Department of Medical Oncology Faculty Papers

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver …

From Latent Manifolds To Targeted Molecular Probes: An Interpretable, Kinome-Scale Generative Machine Learning Framework For Family-Based Kinase Ligand Design, Gennady M. Verkhivker, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

Scaffold-aware artificial intelligence (AI) models enable systematic exploration of chemical space conditioned on protein-interacting ligands, yet the representational principles governing their behavior remain poorly understood. The computational representation of structurally complex kinase small molecules remains a formidable challenge due to the high conservation of ATP active site architecture across the kinome and the topological complexity of structural scaffolds in current generative AI frameworks. In this study, we present a diagnostic, modular and chemistry-first generative framework for design of targeted SRC kinase ligands by integrating ChemVAE-based latent space modeling, a chemically interpretable structural similarity metric (Kinase Likelihood Score), Bayesian optimization, and …

Editorial: Next-Generation Protacs In Oncology And Beyond: Exploring Therapeutic Targets And Their Degraders, Daiqing Liao, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences Faculty Publications

No abstract provided.

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Spatially Distinct Cellular And Molecular Landscapes Define Prognosis In Triple-Negative Breast Cancer, Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne Leblanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam

School of Medicine Faculty Publications

Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] < 3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

Nitroarene-Mediated Photo-Oxidative Deconstruction And Upcycling Of Unsaturated Rubber Waste, Junpeng Wang, Zefeng Wang, Roberto Obergon, Obed Fernando

University Research

Transforming waste polymers into materials with improved properties offers a compelling strategy for advancing the sustainable use of polymers, echoing the Chinese proverb: “Blue comes from indigo but surpasses it in blueness.” Herein, we report a photo-oxidative deconstruction and upcycling method for unsaturated rubber waste. Under 390 nm LED irradiation at room temperature, in the presence of a nitroarene oxidant, diverse unsaturated polymers─including natural rubber, polybutadiene, nitrile rubber, styrene–butadiene rubber, and even cross-linked nitrile gloves─are selectively converted into carbonyl-terminated oligomers. The aldehyde-functionalized products are cross-linked via dynamic imine chemistry with p-phenylenediamine to yield reprocessable elastomers with markedly improved tensile strength …

Optimal Murine Cd4+ T Cell Priming By Mrna-Lipid Nanoparticle Vaccines Requires Endogenous Antigen Processing, Julia E. Rood, Suh Kyung Yoon, Mary K. Heard, Stephen D. Carro, Emma J. Hedgepeth, Mary E. O'Mara, Michael J. Hogan, Nhu Le, Hiromi Muramatsu, Kieu Lam, Petra Schreiner, Coral Kasden, Hansell H. Stedman, Ryan A. Langlois, James Heyes, Norbert Pardi, Laurence C. Eisenlohr

College of Life Sciences Faculty Papers

Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4+ T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine specific CD4+ T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results …