Digital Commons Network^™

A Complete Diploid Human Genome Benchmark For Personalized Genomics, Nancy F. Hansen, Nathan Dwarshuis, Hyun Joo Ji, Arang Rhie, Hailey Loucks, Glennis A. Logsdon, Mitchell R. Vallger, Jessica M. Storer, Juhyun Kim, Eleni Adam, Nicolas Alternose, Dmitry Antipov, Mobin Asri, Sofia Barreira, Stephanie C. Bohaczuk, Andrey V. Bzikadze, Sara A. Carioscia, Andrew Carroll, Kuan-Hao Chao, Yanan Chu, Arun Das, Peter Ebert, Adam English, Mark Fleharty, Laura E. Fleming, Giulio Formenti, Andrea Guarracino, Gabrielle A. Hartley, Katharine Jenike, Jenna Kalleberg, Yu Kang, Robert King, Josipa Lipovac, Mira Mastoras, Matthew W. Mitchell, Shloka Negi, Nathan D. Olson, Keisuke K. Oshima, Luis F. Paulin, Brandon D. Pickett, David Porubsky, Jane Ranchalis, Desh Ranjan, Mikko Rautiainen, Harold Riethman, Robert D. Schnabel, Fritz J. Sedlazeck, Kishwar Shafin, Mile Sikic, Steven J. Solar, Alexander P. Sweeten, Winston Timp, Justin Wagner, Dongahn Yoo, Ying Zhou, Erik Garrison, Evan E. Eichler, Michaeel C. Schatz, Andrew B. Stergachis, Rachel J. O'Neill, Karen H. Miga, Steven L. Salzberg, Sergey Koren, Justin M. Zook, Adam M. Phillippy

School of Medical Diagnostics & Translational Sciences Publications

Human genome sequencing typically relies on mapping reads to a reference genome to call variants, but this approach introduces technical biases, excluding duplicated and structurally polymorphic regions of the genome. To overcome this, we present a telomere-to-telomere genome benchmark with near-perfect accuracy across 99.4% of the diploid HG002 genome. This benchmark adds 701.4 Mb of autosomal sequence and both sex chromosomes (216.8 Mb), which were absent from prior benchmarks. We annotated genes and repeats on both haplotypes, including 19,956 protein-coding genes on the maternal haplotype and 19,190 on the paternal haplotype, and developed new methods to measure the accuracy of …

Growing South Dakota (Winter 2026), College Of Agriculture, Food And Environmental Sciences

Growing South Dakota (Publication of the College of Agriculture, Food and Environmental Sciences)

[Page] 2 International Year of Rangelands and Pastoralists: South Dakota rangelands take center stage
[Page] 4 The professor and the soil
[Page] 8 Range ready: Helping students bridge the gap between conservation and agriculture
[Page] 9 Resilient rangelands: Native Plant Initiative’s role in reviving South Dakota’s prairies
[Page] 10 Jackrabbits lead the charge in bison research and education
[Page] 12 Agricultural and biosystems engineering celebrates century of education
[Page] 16 SDSU Quarter Scale Tractor Club: An impact beyond awards
[Page] 18 Building a legacy of opportunity: Karen D. Stuck Endowment strengthens agricultural communication program at South Dakota State University
[Page] …

Summer Research Fellowship Project Descriptions 2026, Clark Science Center's Summer Research Fellows Program

SURF Abstracts (Women in Science)

A summary of research done by Smith College’s 2026 Summer Research Fellowship (SURF) Program participants. Ever since its 1967 start, SURF has been a cornerstone of Smith’s science education. Supervised by faculty mentor-advisors drawn from the Clark Science Center and connected to its eighteen science, mathematics, and engineering departments and programs and associated centers and units. At summer’s end, SURF participants were asked to summarize their research experiences for this publication.

Effect Of Substrate Dispersion Method And Particle Size On In Vitro Digestibility, Gas Production Kinetics And Composition, And Fermentation Characteristics In Different Feed Types, Luiz C. O. Sousa, Ellem M. A. Matos, Ronald J. Trotta, Edenio Detmann, David L. Harmon

Animal and Food Sciences Faculty Publications

Our objective was to evaluate the influence of substrate dispersion method and particle size on in vitro digestibility, gas production kinetics and composition, and fermentation characteristics of different feed types. Alfalfa hay, tall fescue hay, ground corn, soybean meal, and a total mixed ration (TMR) were used as substrates. Treatments were designed according to a 2 × 2 × 5 factorial arrangement: two substrate dispersion methods (loose substrate and in filter bags), two particle sizes (1 mm and 2 mm), and five feeds. Filter bags decreased (P ≤ 0.001) digestibility and gas production compared with loose samples. Filter bags decreased …

Building A Cell Specific System For In Vivo Rna Imaging Of The Endogenous Actin Gene In C. Elegans, Jasmine A. Huerta Canete

Theses and Dissertations

Messenger RNA (mRNA) plays a crucial role in protein synthesis and cellular processes, important for the development of cells such as neurons. When dysregulation occurs, it can lead to outcomes such as aberrant translation, causing neurodegenerative conditions to arise. Unfortunately, the localization of mRNA in an in vivo cell specific manner is still not understood. To address this, we decided to develop a cell-specific system to image RNA in vivo, within the organism known as C. elegans with a focus on the actin gene. The Actin gene encodes for an important cytoskeleton protein expressed ubiquitously, vital for the cell …

The Effects Of Hyperthyroidism On Mouse Corneal Innervation: Implications For Human Cornea Re-Innervation, Anjali Malali

Research Honors

To test the effects of elevated TH during cornea development, our lab has collaborated with Dr. Juan Davila (University of Illinois Urbana-Champaign) to develop an embryonic mouse model of hyperthyroidism. Embryos were exposed to high levels of TH in utero by adding TH to the pregnant mother’s drinking water. Upon collection of the embryos, elevated blood thyroid levels in the pregnant mother were analyzed with an enzyme-linked immunosorbent assay (ELISA), and eye tissues were collected and preserved for analysis of corneal nerve innervation patterns. By utilizing immunohistochemistry in order to visualize corneal innervation in mouse embryos, this project studied whether …

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 …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

Faculty, Staff and Student Publications

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by …

Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum

Faculty Publications

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and …

Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani

Faculty, Staff and Student Publications

This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …

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 …

Mxene-Enabled Wearable Biosensors: A Design Framework For Autonomous Biosensing, Jegan Rajendran, Gymama Slaughter

Center for Bioelectronics Publications

MXenes, a rapidly expanding family of two-dimensional transition metal carbides and nitrides, have emerged as leading materials for wearable bioelectronics due to their metallic conductivity, termination-rich surfaces, mechanical compliance, and tunable interlayer structures. However, wearable biosensor performance does not arise from conductivity alone, but from coupled interactions among surface termination chemistry, heterointerface engineering, hierarchical architecture, and device integration under dynamic physiological conditions. This review establishes a predictive structure-interface-device framework linking MXene chemistry to system-level performance across electrochemical, mechanical, gas, optical, and energy-storage modalities. We analyze how termination-controlled adsorption governs charge transfer and selectivity, how heterojunction formation modulates carrier density and …

Ion-Imprinted Polymer-Based Sensors For Toxic Metal-Ion Detection In Water: Coordination Chemistry, Transduction Strategies, And Environmental Applications, Ghita Yammouri, Gymama Slaughter

Center for Bioelectronics Publications

Toxic metal contamination in aquatic environments remains a persistent threat to human health and ecosystems. Yet, the high cost, infrastructure demands, and centralized nature of conventional analytical methods constrain routine monitoring. Ion-imprinted polymers (IIPs), a subclass of molecularly imprinted polymers, have emerged as promising synthetic recognition materials for metal-ion sensing because they generate coordination-defined binding sites with high selectivity, chemical stability, low cost, and reusability. This review summarizes recent advances in Ion-imprinted polymer (IIP)-based sensing technologies for toxic metal-ion detection in water from 2016 to 2026. It examines the fundamental recognition chemistry of IIPs, major synthesis strategies used to generate …

Ecological Feedbacks In The Earth System, Eugene J. Murphy, Jessica J. Williams, Isla H. Myers-Smith, Vivienne P. Groner, David M. P. Jacoby, Lester Kwiatkowski, Jess Melbourne-Thomas, Emma Ransome, Cristina Banks-Leite, Laurent Bopp, Marion Gehlen, Eileen E. Hofmann, Babette Hoogakker, Nadine M. Johnston, Yadvinder Malhi, Emma L. Cavan

CCPO Publications

Ecological feedbacks are fundamental features of the Earth system, affecting physical processes and chemical cycles. Our understanding of the interactions underlying these feedbacks at different spatial and temporal scales and the extent to which feedbacks affect Earth system functioning remains limited. Climate change and other anthropogenic pressures are already negatively affecting ecological processes in marine, freshwater, and terrestrial ecosystems. These will most likely be amplified in the coming decades under our current warming and socioeconomic pathways. The knock-on impacts on ecological feedbacks have the potential to cause rapid perturbations to the Earth system, and may significantly impact the structure and …

Agricultural Productivity Under Energy Development: Insights From California, Wai Yan Siu, Sherzod B. Akhundjanov

ODU Articles

This paper examines how agricultural productivity patterns in Kern County, California, a leading region for both agricultural production and oil and gas development, co-vary with the spatial and temporal expansion of hydraulic fracturing and associated energy infrastructure. Using parcel- and county-level analyses, we characterize how agricultural productivity differs across proximity to energy development and across spatial scales. The results reveal spatially heterogeneous and scale-dependent patterns: parcel-level evidence indicates lower Enhanced Vegetation Index-based vegetation productivity within the 20-mile proximity zone around fracking wells, while county-level results show heterogeneous crop-specific yield changes during the post-expansion period. Together, these findings highlight the importance …

External Validation Of A Knowledge-Based Clinical Toxicology Consultant For Diagnosing Single Exposures, Hugo Lerogeron, Joel D. Schipper, Jay L. Schauben, Laurent Guéguen, Valentine Lacotte, Kim An Nguyen

Publications

Introduction

Clinical prediction models assist healthcare providers in estimating disease likelihood using multiple patient-specific factors. While these models are increasingly used, few undergo the essential process of external validation, which limits their clinical utility. In toxicology, timely diagnosis is crucial and expertise scarce, making knowledge-based systems an excellent choice to support medical decision making. A knowledge-based system developed using data from the Florida Poison Information Center Network has shown promise but lacks external validation. This study aims to evaluate its performance using data from the Lyon Poison Information Center to assess its generalizability

Methods

To externally validate the Florida diagnostic …

Aquatic Invasive Species Survey And Treatment On Lake Umatilla And Lake Celilo 2024-2025 Report, Jacob Rose, Gabriel E. Campbell

Center for Lakes and Reservoirs Publications and Presentations

Flowering Rush (Butomus umbellatus) is an invasive aquatic plant in the Pacific Northwest that threatens salmon habitat. The Center for Lakes and Reservoirs staff surveyed for this and other aquatic species from 2024 and 2025 in the Columbia River in Lake Umatilla and Lake Celilo. This document summarizes their survey efforts including their protocols, data, and small-scale removal efforts.

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

Updates To Version 1.0 Of The Four‐Dimensional Ecology Education Framework Create Version 1.1., Christopher W. Beck, Loren B. Byrne, Jennifer Doherty, Amanda E. Sorensen, Et Al.

Arts & Sciences Faculty Publications

Since its introduction in 2018, the Four-Dimensional Ecology Education (4DEE) Framework has advanced ecology education. Yet, ecology educators have had different understandings of aspects of the Framework. Here, we describe the updates to the original Framework that aim to provide more clarity. Specifically, we describe higher-level changes in how the Framework is presented on the 4DEE website, changes to some of the elements within the dimensions, mostly in the Human–Environment Interactions dimension, and perhaps most substantively, replacing the lists of subelements with more descriptive paragraphs that explain the intent of the elements. We hope that these updates will promote the …

Impact Of Tactical Breathing On Marksmanship And Cognitive Function After Anaerobic Fatigue In Law Enforcement Personnel, Jackson D. Gilleland

College of Graduate Studies: Theses & Dissertations

Background: Tactical breathing is commonly used in law enforcement training to regulate stress, yet limited evidence exists regarding its acute effectiveness following physical fatigue. Purpose: To examine whether a brief tactical breathing intervention improves shooting performance and heart rate variability (HRV) following anaerobic fatigue in law enforcement officers. Methods: Thirty-eight officers completed baseline HR/HRV and a shoot/no-shoot scenario, followed by a maximal 500-m row and post-fatigue shooting. Participants were assigned to either a control group or a tactical breathing group, which received brief instruction and coaching before post-testing. Results: No significant between-group differences were observed for A-zone accuracy, shot time, …

Bio-Orthogonal Chemistry-Based Strategy To Turn-On And Turn-Off Crispr-Cas9 Gene Editing In Solution And In Live Cells, Bhoomika Pandit

Electronic Theses & Dissertations (2024 - present)

The CRISPR–Cas9 system is a widely popular tool for genome engineering. There is a strong interest in developing tools for temporal control of CRISPR-Cas9 activity to address some of the challenges and to broaden the scope of potential applications. In this thesis I describe two biorthogonal based approaches to either Turn-ON and Turn-OFF CRISPR-Cas9 gene editing.

In first project work I describe a bio-orthogonal chemistry-based approach to Turn-ON Cas9 nuclease activity with temporal precision. We report a TCO-acylimidazole reagent that acylates 2′-OH groups of RNA. Poly-acylation (“cloaking”) of RNA was optimized in vitro using a model 18-nt oligonucleotide, as well …

Stem Cell-Derived Developmental Models For Translational Evaluation Of Disease And Therapy, Maria B. Paredes-Espinosa

Electronic Theses & Dissertations (2024 - present)

Human development as well as congenital and adult diseases emerge from coordinated interactions among multiple cell types, regulatory programs, and tissue compartments that remain largely unresolved. Conventional simple lineage-restricted in vitro systems poorly capture this complexity. My dissertation uses human stem cell-derived developmental models to study human cardiac morphogenesis and heart diseases and application of a networked neuron platform to explore senescence-associated neurodegeneration impact on Alzheimer’s neurons.

Elongating multi-lineage organized cardiac (EMLOC) gastruloids are a synthetic embryology model that co-generates contractile cardiomyocyte populations alongside mesenchymal, endothelial, epicardial-like, neural crest-associated, and neuronal cells within a shared in vitro developmental environment. Single-cell …

The Chemistry Of Red Lipstick: The Impact Red Lipstick Has On Society, Lilliana Weldeslassie

Electronic Theses & Dissertations (2024 - present)

Cosmetic chemistry is deeply embedded in everyday life, shaping the products people use from morning to night. Among these, red lipstick stands out as a formulation that blends complex chemistry with a cultural meaning. This thesis examines the scientific foundations of red lipstick through its chemical composition, pigment structure, toxicological history, analytical methods, and evolving sustainability practices. Historically, red lipsticks relied on high-risk ingredients such as lead, mercury, and other toxic metals, reflecting an era before chemical safety and regulatory oversight were incorporated.²¹ Modern formulations have established safer synthetic dyes, natural waxes, plant-based oils, and stabilizers created to optimize …

Combating Antibiotic Resistance With Plasmid-Dependent Phages, Rhiannon T. Mariano

Electronic Theses & Dissertations (2024 - present)

The alarming rise of carbapenem-resistant bacteria poses an urgent global health threat, driven in large part by the horizontal spread of carbapenemase-encoding plasmids (Ma et al., 2023). These plasmids are often highly mobile and transmissible, enabling rapid dissemination of resistance genes across diverse bacterial populations. Their mobility is largely mediated by conjugation, a process dependent on the formation of pili, which serve as physical bridges for plasmid transfer between cells (Murray et al. 2022; San Millan and MacLean 2017; Virolle et al. 2020). Beyond their role in gene exchange, these pili also act as entry points for a unique class …

Generating Concentrated Ring Polymers Through Supercoiled And Open Circle Pdna Isoform Separation, Kelsey E. Hodsdon

Honors Theses and Capstones

DNA can serve as a model polymer due to its high uniformity compared to synthetic polymers. Plasmid DNA (pDNA) in particular offers a well-defined, low-dispersity model for studying topologically uniform systems of a cyclic nature. pDNA has unique isoforms known as open circle (OC) and supercoiled (SC). Using fast protein liquid chromatography (FPLC), specifically anion exchange chromatography (AEX), these OC and SC isoforms can be separated in order to access their unique material properties. Our lab was able to yield the pure SC isoform. However, OC isoform separation has been more challenging. Various difficulties arose during this process, including imaging …

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 …

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 …

Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-Of-Origin In Esophageal Squamous Cell Carcinoma, Kyung-Pil Ko, Jie Zhang, Sohee Jun, Jae-Il Park

Faculty, Staff and Student Publications

Background and aims: Understanding the cells of origin is essential for overcoming therapy resistance and improving early intervention strategies in esophageal squamous cell carcinoma (ESCC). Despite recent advances in genomic profiling, the precise cellular hierarchies and molecular programs driving ESCC initiation remain poorly defined.

Methods: We utilized machine learning-based single-cell trajectory analysis on 4-nitroquinoline 1-oxide-induced murine models and genetically engineered organoids to identify cellular lineages during tumorigenesis. Combined with gene regulatory network analysis, we identified transcriptional drivers of tumor initiation and employed transcriptome-based drug repurposing to predict compounds targeting these initiating populations.

Results: Our analyses revealed multiple distinct epithelial clusters …

A Critical Perspective On The Society Of Environmental Toxicology And Chemistry's Adherence To Founding Principles— Opportunities For The Future, Barnett A. Rattner, Annegaaike Leopold, Carys L. Mitchelmore, Glenn W. Suter, Mark S. Johnson, Adriana C. Bejarano, Lawrence A. Kapustka, Niranjana Krishnan, Derek C. G. Muir, Beatrice O. Opeolu, Martha Georgina Orozco-Medina, April Reed, Bruce W. Vigon, Adam R. Wronski

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

The Society of Environmental Toxicology and Chemistry (SETAC) is a global organization whose mission is the advancement of environmental science and management through collaboration, leadership, communication and education. On SETAC's 45th anniversary, the following question was raised: Are the 1979 founding principles of SETAC, multidisciplinary approaches to solving environmental problems, multisector engagement and scientific objectivity, still useful, adequate and effective in fulfilling its mission? In a special session held at the 45th Annual Meeting in Fort Worth, Texas, United States, a critical evaluation of the founding principles was initiated by reviewing SETAC's history and ongoing activities, and recommendations were made …