Digital Commons Network^™

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Corticotropin-Releasing Factor Neurons In The Bed Nucleus Of The Stria Terminalis Modulate Avoidance Behaviors And Feeding, Juan Manuel Romero, Shae-Marie Stafford-Trujillo, Mitzy Mendoza, Pey-Shyuan Chin, Snigdha Srivastava, Mikhail Kochukov, Qingchun Tong, Benjamin Russell Arenkiel

The Brown Foundation: Institute of Molecular Medicine

Introduction: Animals rely on defensive avoidance of exposed or potentially threatening environments as a fundamental survival strategy, often expressing this behavior as thigmotaxis, or a preference for the periphery of an open space. However, researchers still do not understand how neural circuits coordinate avoidance behavior with competing physiological drives such as feeding. In this study, we investigate how corticotropin-releasing factor (CRF)-expressing neurons in the bed nucleus of the stria terminalis (BNST) integrate environmental avoidance and feeding behavior.

Methods: We used adult male and female mice and applied fiber photometry to monitor BNST CRF neuronal activity in vivo. We performed both …

Ventilation-Perfusion Scan: A Functional Imaging Approach To Regional Lung Disease In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Introduction: As a rare genetic disorder defined by defective ciliary motility, Primary Ciliary Dyskinesia (PCD) leads to chronic respiratory complications. A founder variant in the RSPH4A [c.921+3_921+6delAAGT] gene, common in Puerto Rico, impairs ciliary function and contributes to progressive lung disease. Today, the clinical value of ventilation/perfusion (V/Q) scans in PCD has not been thoroughly investigated as well as pulmonary function tests (PFTs) and chest imaging. To explore the role and clinical utility of V/Q scans in PCD.

Methods: Retrospective evaluation of pulmonary function tests, chest imaging, and Tc-99m DTPA ventilation and Tc-99m MAA perfusion scans in ten patients with …

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 …

“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 …

Examining Widely Held Propositions On Human Dietary Protein Needs And Benefits: A Critical Review Of The Science That Shapes Both The Data And Our Understanding Of An Essential Macronutrient, Mitchell M Kanter, Sally Aaron, Steven N Austad, Andrew W Brown, Nicholas A Burd, Wayne W Campbell, Mark Cope, Teresa A Davis, John W Erdman, Miguel Freitas, Kristen Hicks-Roof, Samuel Klein, Wantanee Kriengsinyos, Dudley W Lamming, Donald K Layman, Heather J Leidy, Kevin C Maki, Richard D Mattes, Shalene Mcneill, Daniel R Moore, Stefan M Pasiakos, Stuart M Phillips, David Raubenheimer, Wendy Reinhardt, Nancy R Rodriguez, Stephen Simpson, Hans H Stein, Luc J C Van Loon, Connie M Weaver, David B Allison

Children’s Nutrition Research Center Staff Publications

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, …

Cross-Sectional And Longitudinal Relationships Between Abdominal Fat Depots And Cardiometabolic Risk In A Sample Of Mexican Adolescents, Luis Ortíz-Hernández, Erica G Soltero, Miguel Camejo, Jesús Valdes

Children’s Nutrition Research Center Staff Publications

Background: The relationship between abdominal fat depots and cardiometabolic risk among youth is inconclusive due to the cross-sectional nature of existing studies and limitations in assessment methods. In this study, we examined cross-sectional and longitudinal associations of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with cardiometabolic risk indicators among Mexican adolescents.

Methods: Participants (n = 169 at baseline and 134 at follow-up) were assessed for diastolic or systolic blood pressure (DBP or SBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, and insulin. VAT and SAT were measured using magnetic resonance imaging. Measures …

Artificial Light At Night Extends Pollen Season And Elevates Allergen Exposure, Brandt Geist, Lin Meng, Daniel S W Katz, Huidong Li, Franz Hölker, Qian Xiao

Faculty, Staff and Student Publications

Artificial light at night (ALAN), a growing environmental stressor in urban ecosystems, disrupts natural light-dark cycles and alters plant phenological events such as leaf-out and flowering. However, the extent to which ALAN influences airborne pollen season timing and exacerbates allergy-related health risks remains largely understudied. This study investigates how ALAN influences the timing and duration of the airborne pollen season across the Northeastern United States from 2012 to 2023 and the consequences of allergenic pollen exposure. Using daily pollen concentrations from the National Allergy Bureau, ALAN data from the Visible Infrared Imaging Radiometer Suite product, and gridded Daymet climate data, …

Plasma Proteomic Profile Of Dietary Potassium And Incident Ckd, Jiaqi Yang, Lauren Bernard, Jingsha Chen, Valerie K Sullivan, Bing Yu, Eugene P Rhee, Paul A Welling, Casey M Rebholz

Faculty, Staff and Student Publications

Background:: There is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood.

Methods:: Atherosclerosis Risk in Communities study participants at visit 3 (1993–1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD).

Results:: …

Targeting Nuclear Receptors In Muscular Dystrophies And Regenerative Myogenesis, Eira Mann, Hoang Vu, Vihang A Narkar, Yu Liu

The Brown Foundation: Institute of Molecular Medicine

Skeletal muscle is a highly plastic tissue with a robust capacity for regeneration, largely driven by resident satellite cells. Muscular dystrophies comprise a heterogeneous group of inherited disorders characterized by progressive muscle degeneration, chronic inflammation, and impaired regenerative capacity. Despite well-defined genetic etiologies, effective disease-modifying therapies for these disorders, as well as many acquired myopathies, remain limited. Emerging evidence identifies nuclear receptors (NRs) as key regulators of skeletal muscle homeostasis, integrating hormonal, metabolic, and environmental signals to control transcriptional programs governing mitochondrial function, metabolism, inflammation, and myogenesis. In this review, we summarize the diverse roles and mechanisms of action of …

Immune Checkpoint Inhibitor-Induced Cardiotoxicity: From Immune Mechanisms To Clinical Surveillance And Targeted Therapies, Nathan K Chen, Kathryn D Hok, Narsi Chokshi, Anthony Shadid, Haydn E Rich, Lavanya Gunamalai, Marie-Francoise Doursout, Nirmal K Banda, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across a broad range of malignancies by restoring antitumor immunity through blockade of key inhibitory immune pathways, including programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Yet the same widespread immune activation that drives their therapeutic benefit renders patients susceptible to immune-related adverse events (irAEs). Among these cardiovascular toxicities have emerged as a particularly critical concern, drawing growing attention within the evolving field of cardio-oncology. ICI-associated cardiotoxicity encompasses a broad clinical spectrum, ranging from myocarditis and pericarditis to arrhythmias, heart failure, and vascular complications. Of these, …

A User-Friendly Graphical User Interface For Paw Touch Classification In Rodent Cylinder Testing, Tyler R Johnson, Katherine D Zerefos, Dawn M Taylor

Faculty, Staff and Student Publications

In unilateral rodent models of disease or injury, deficits are induced in only one side of the body, allowing the difference in right versus left limb usage to serve as a metric of disease/injury severity and recovery with various treatments. Unilateral rat models are commonly used for conditions such as Parkinson’s disease (via the neurotoxin 6-hydroxydopamine, 6-OHDA), stroke, and traumatic brain injury, as well as cervical spinal cord injury and peripheral nerve damage. The ‘cylinder test’ has been used for over two decades as a reliable metric of asymmetry in forelimb usage. In this test, videos are taken of the …

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, …

Mitochondrial Dysfunction In Alzheimer’S Disease And Related Sex Differences, Afzal Misrani, Conelius Ngwa, Fudong Liu

Faculty, Staff and Student Publications

Alzheimer's disease (AD), the most common form of dementia, accounts for 70% of cases and remains a major healthcare challenge due to its rising prevalence and lack of disease-modifying treatments. Clinically, AD is a sexually dimorphic disease. Women exhibit more rapid cognitive decline and accelerated brain atrophy during mild cognitive impairment and early dementia, whereas men more frequently present cardiovascular comorbidities, earlier mitochondrial dysfunction, and greater neuropsychiatric symptoms. AD is marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss, with mitochondrial dysfunction emerging as a key early contributor that exhibits sex specific phenotypes. Mitochondria are vital for neuronal …

Retrospective Longitudinal Analysis Of Blood Microrna-7-5p As A Possible Progression Biomarker In People With Parkinson’S Disease, Shayan Abdollah Zadegan, Corrine Hutchinson, Chiamaka Onuigbo, Juan D Martinez-Lemus, Laura Talbot, E Jeffrey Metter, Marie-Francoise Doursout, Emily Tharp, Jessika Suescun, Mohammad Shahnawaz, Timothy M Ellmore, Mya Schiess, Christopher Adams

Faculty, Staff and Student Publications

Background: MicroRNA-7-5p (miR-7-5p) may play a neuroprotective role in people with Parkinson's disease (PwP), as it has been found to regulate α-synuclein (α-syn) and the NLRP3 inflammasome in animal models of Parkinson's disease (PD).

Objective: The study aimed to investigate the use of miR-7-5p as a potential biomarker for disease progression in PwP by correlating it with time, clinical measures, and neurofilament light chain (NfL).

Methods: We performed a longitudinal retrospective analysis of blood miR-7-5p levels in 303 de novo PwP and 159 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort. In PwP, a linear mixed-effects …

Glaucoma Risk With Metformin And Sulfonylurea Therapies In Type 2 Diabetes: A Retrospective Cohort Study., Jared Lim, Jingru Zhou, Hulin Wu, Ziqi Liu, David A Lee

Faculty, Staff and Student Publications

Background: Research on metformin, sulfonylureas, and open-angle glaucoma risk in type 2 diabetes mellitus (T2DM) has yielded inconsistent findings. This study examined associations between hypoglycemic treatments and glaucoma diagnosis rates.

Methods: This retrospective cohort study analyzed electronic health records of newly diagnosed T2DM patients from the Merative™ Explorys® Therapeutic Dataset (2010-2022), comparing three groups: metformin monotherapy, sulfonylureas plus metformin combination, and untreated controls. Propensity score matching balanced demographics, glycemic control, body mass index, blood pressure, lipid levels, and comorbidities. Cox proportional hazards models calculated adjusted hazard ratios for incident glaucoma.

Results: After 1:1 propensity score matching, metformin monotherapy (N=100,387) showed …

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.

Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …

Proliferation And Apoptosis Adaptor Protein 15 (Pea15), A Potential Oncogenic Regulator Of Vhl And Hif1a Identified Through Proteomic Analysis In Hepatocellular Carcinoma, Yun Seong Jeong, Ji-Hyun Shin, Soo Mi Kim, Bo Hwa Sohn, Sun Young Yim, Ji Hoon Kim, Jae Jun Shim, Sung Hwan Lee, Yun Shin Chun, Sunyoung S Lee, Hui Dai, Ahmed Kaseb, Koo Jeong Kang, Holger K Eltzschig, A Robert Macleod, Xiaolin Luo, Alexey Revenko, Youngsoo Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Hyperglycemia In Combination With Excess Fat Intake Promotes Renal Pyroptosis And Fibrosis Through Gα12-Dependent Endoplasmic Reticulum Stress, Muhammad Sohaib Khan, Boram Kim, Yerim Jeon, Jihoon Tak, Yun Seok Kim, Sang Gil Lee, Eun Byul Lee, Chang-Hoon Lee, Cheol Bin Eom, Hyun Sook Lee, Hyeon-Ki Jang, Nakyeom Lee, Jeong Hae Kie, Jee Myung Yang, Yoon Mee Yang, Sang Geon Kim

Faculty, Staff and Student Publications

Background: Chronic exposure to free fatty acids (FFAs) and glucose may disrupt metabolic homeostasis and initiate pathological processes. This study investigated the effects of hyperglycemia and fat overload on renal endoplasmic reticulum (ER) stress, pyroptosis and fibrogenesis in mice and the underlying basis. We hypothesized that the combined insult would more severely induce Gα12-dependent ER stress and renal complications.

Methods: Mice were subjected to either high fat diet (HFD)+streptozotocin (STZ), or STZ treatment, and AZ2 was used as an anti-diabetic agent. Blood sera were used for blood biochemistry, and tissues were employed for RNA sequencing, immunoblottings, TEM, histology and immunohistochemistry. …

Remission Of Recalcitrant Pyoderma Gangrenosum Following Chemotherapy For Iatrogenic Kaposi Sarcoma, Noel X Yang, T Austin Black, Adan A Rios, Megan N Rogge

Faculty, Staff and Student Publications

No abstract provided.

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Digital Communication Strategies For Culinary Medicine In Cancer Prevention And Survivorship: Information-Seeking Habits And Content Preferences Of Online Cooking Media Among Adults Participating In Four Cancer Prevention And Control Cohort Studies, Margaret Raber, Sara Fares, Maria Vazquez, Larkin Strong, Carrie Daniel-Macdougall, Lorna Mcneill, Karen Basen-Engquist

Faculty, Staff and Student Publications

Introduction

Poor diet and excess weight have been linked to increased risk for at least 13 types of cancer. Culinary medicine utilizes experiential cooking skill development to improve individuals’ capacity for healthy eating. Digital communication strategies offer pathways for scalable culinary medicine interventions, but little research has explored how online cooking tools could be leveraged for cancer prevention messaging. We conducted a cross-sectional survey study exploring online cooking information-seeking habits and content preferences among participants in four cancer prevention and control cohorts to inform future digital culinary medicine interventions.

Methods

A cross-sectional survey study was conducted with a convenience sample …

T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan

Faculty, Staff and Student Publications

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay

Faculty, Staff and Student Publications

Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen …