Digital Commons Network^™

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

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 …

Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner

Faculty, Staff and Student Publications

Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

Recent Technological Advances In Monitoring And Neuromodulation Of Non-Malignant And Neurogenic Bladder Conditions, Chang Liu, Yifan Wang, Mario Romero-Ortega, Argyrios Stampas, Yingchun Zhang, Philippe Zimmern, Zhengwei Li

Faculty, Staff and Student Publications

Neurogenic bladder and lower urinary tract (LUT) dysfunctions encompass a wide variety of urinary disorders resulting from nervous system impairments. Unfortunately, conventional treatments are still limited and can have significant complication rates, especially when stent implantations or other surgical procedures are involved. Therefore, there is a critical need to develop novel therapeutic strategies and pharmacological approaches to address these challenging urological conditions. Recent technological advances offer promising solutions to overcome some of these challenges faced by patients with bladder and LUT dysfunction. This review summarizes recent progress in advanced urotechnologies, focusing on bladder monitoring and neuromodulation approaches, advanced medical instruments …

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Nemolizumab As An Alternative Therapeutic Option For Indolent Systemic Mastocytosis, Sezim Minbaeva, Stephen K Tyring

Faculty, Staff and Student Publications

Indolent systemic mastocytosis (ISM) is a clonal mast cell disorder characterized by recurrent symptoms that can persist despite treatment with antihistamines, leukotriene antagonists, and mast cell stabilizers. Treatment options are limited when symptoms remain refractory, and avapritinib is contraindicated or declined. We describe the case of a 62-year-old female with an 11-year history of ISM who developed worsening pruritus and urticaria despite extensive conservative and biologic therapies, including topical corticosteroids, hydroxyzine, montelukast, omalizumab, and dupilumab. Given her history of stroke, she declined avapritinib. Nemolizumab was initiated with a 60 mg loading dose followed by 30 mg every four weeks. After …

Causal Functional Mediation Analysis With An Application To Functional Magnetic Resonance Imaging Data, Yi Zhao, Xi Luo, Michael E Sobel, Martin A Lindquist, Brian S Caffo

Faculty, Staff and Student Publications

A primary goal of task-based functional magnetic resonance imaging (fMRI) studies is to quantify the effective connectivity between brain regions when stimuli are presented. Assessing the dynamics of effective connectivity has attracted increasing attention. Causal mediation analysis serves as a widely implemented tool aiming to delineate the mechanism between task stimuli and brain activations. However, the case, where the treatment, mediator, and outcome are continuous functions, has not been studied. Causal mediation analysis for functional data is considered. Semiparametric functional linear structural equation models are introduced and causal assumptions are discussed. The proposed models allow for the estimation of individual …

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Dcpr: A Deep Learning Framework For Circadian Phase Reconstruction, Xiao Han, Xiaochen Cen, Zhijin Li, Xiaobo Zhou, Zhiwei Ji

Faculty, Staff and Student Publications

Background: The circadian clock is an evolutionarily conserved system that orchestrates 24-h physiological rhythms through transcriptional and translational feedback loops. Mounting evidence suggests a bidirectional relationship between circadian rhythm alteration and disease progression, positioning the circadian clock as a potential therapeutic target. Due to the scarcity of high-resolution temporal omics data, it remains very challenging to elucidate the underlying regulatory mechanisms of the circadian system. As a practical alternative, public untimed transcriptomic datasets offer the potential to infer gene expression oscillations retrospectively. However, existing computational approaches for circadian phase estimation often suffer from limited predictive accuracy, reducing their ability to …

Effects Of Auricular Point Acupressure On Inflammatory Signaling In Chronic Low Back Pain: A Secondary Analysis Of A Randomized Controlled Trial, Nada Lukkahatai, Hongyu Wang, Xinran Huang, Wanqi Chen, Hulin Wu, Jennifer Kawi, Zhiyin Yu, Constance M Johnson, Paul Christo

Faculty, Staff and Student Publications

Objective: Auricular point acupressure (APA) has shown promise for pain relief, but its biological mechanisms remain unclear. This study examined the effects of APA on inflammatory cytokines and explored the relationships between changes in inflammatory markers and clinical outcomes in older adults with chronic low back pain (cLBP).

Method: This secondary analysis utilized plasma samples from a three-arm randomized controlled trial (RCT) (NCT03589703) with 272 participants aged 65 years and older with cLBP. The participants were randomly assigned (1:1:1) to the targeted APA (T-APA), nontargeted APA (NT-APA), or education control (CG) groups for four weeks. Cytokine levels were …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …

Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Jessica N Vincent, Joy M Schmitz, Scott D Lane

Faculty, Staff and Student Publications

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the …

Braingenebot: A Gpt-Engineered, User-Driven Genetic Data Exploration With Polygenic Risk Scores Ranking In Alzheimer’S Disease, Guan Ou, Zhongming Zhao

Faculty, Staff and Student Publications

Background

Polygenic risk scores (PGSs) aggregate the effects of multiple genetic variants to attribute to disease susceptibility, and have been applied to numerous complex diseases including Alzheimer's disease (AD). However, as omics and phenotypic data grow exponentially, reconciling findings across studies with differing ancestral backgrounds, study designs, and statistical methodologies remains a pressing issue. Efficiently extracting biologically relevant insights from this expanding body of data is equally challenging, especially for diseases driven by complex interactions among genetic, environmental, and lifestyle factors.

Method

To address these challenges, we introduce BrainGeneBot, an AI‐driven chatbot framework that automates genetic data analysis and bridges …

Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju

Faculty, Staff and Student Publications

No abstract provided.

Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie

Faculty, Staff and Student Publications

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7-14 days of age, designated "transitional ages," as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …

Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu

Faculty, Staff and Student Publications

Background: Epithelial cell adhesion molecule (EpCAM) is a pleotropic transmembrane glycoprotein comprising an extracellular domain (EpEX), a single transmembrane domain, and an intracellular domain (EpICD). For several types of cancer, high EpCAM expression is associated with tumor progression, metastasis, immune evasion, and overall poor prognosis. A rare but aggressive form of thyroid cancer, anaplastic thyroid cancer (ATC), has a mean survival time of only 3–6 months after diagnosis.

Methods: The levels of EpEX and EpICD cleavage in clinical patient samples was evaluated by using tissue microarray. Capture enzyme-linked immunosorbent assay (ELISA) was conducted to explore the of shedding EpEX and …

Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube

Faculty, Staff and Student Publications

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer …

Development Of A Procedure For Prion Surveillance In The Laboratory Setting, Damian Gorski, Isaac Schauer, Kane Spicker, Ananya Tupaki-Sreepurna, Fei Wang, Claudio Soto, Sandra Pritzkow

Faculty, Staff and Student Publications

Infectious prions readily adhere to common surfaces, retain infectivity, and are highly resistant to conventional decontamination, posing significant biosafety challenges in the medical and research environments. Recent occupational exposures underscore the urgency of improving safety measures. Here, we describe an approach combining foam-swab surface sampling and protein misfolding cyclic amplification to enhance prion surveillance. Our results demonstrate the ability to detect prions most relevant to human health directly from contaminated surfaces, even at 100 million-fold dilutions of the brain. We applied our method to assess the completeness of prion decontamination and show that high prion quantities can resist even approved …

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …

A Systematic Characterization Of Fibroblast Subtypes And Heterogeneity, Xiuli Zhu, Hongen Kang, Zhongming Zhao, Peilin Jia

Faculty, Staff and Student Publications

Fibroblasts are essential components in development, disease, and treatment response, yet their diversity and function remain incompletely understood. Here, we constructed a comprehensive fibroblast landscape by integrating large-scale single-cell and single-nucleus RNA sequencing datasets spanning 60 major human organs and tissues across various developmental stages and biological conditions. We identified 16 fibroblast subtypes and systematically characterized their tissue specificities, transcriptional heterogeneity, and cell states. Further analyses revealed distinct fibroblast subtypes associated with pluripotency and senescence across tissues. Leveraging the well-defined fibroblast atlas, we demonstrated that different fibroblast subtypes were associated with various complex traits such as anthropometric and immune diseases. …

Single-Nucleus Multiomics Reveals The Disrupted Regulatory Programs In Three Brain Regions Of Sporadic Early-Onset Alzheimer’S Disease, Andi Liu, Citu Citu, Nitesh Enduru, Xian Chen, Chia-Hao Tung, Tirthankar Sinha, Sofia E Sepulveda, Astrid M Manuel, Damian Gorski, Brisa S Fernandes, Meifang Yu, Paul E Schulz, Lukas M Simon, Claudio Soto, Zhongming Zhao

Faculty, Staff and Student Publications

Sporadic early-onset Alzheimer’s disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type–specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized eight conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells …

Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. …