Digital Commons Network^™

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

Spatial2gwas: A Database For Linking Spatial Transcriptomic Regions With Gwas Traits, Xi Hu, Aoqi Wang, Huan Yu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial heterogeneity of gene expression within tissue regions has a critical influence on biological functions, thereby affecting disease pathogenesis. However, systematic associations between spatially resolved transcriptomes and phenotypes, especially in complex diseases, remain underexplored. Here, we developed spatial2GWAS (http://www.spatial2gwas.cn), a comprehensive resource linking spatial transcriptomic (ST) regions with GWAS traits. In the database, we collected 1196 ST slices (human and mouse) from five technologies and 812 GWAS traits spanning 18 phenotype categories and identified 29 701 ST slice-GWAS trait pairs containing 47 492 significant regions. Functional analyses reveal distinct patterns of cell type composition, gene expression, GO/KEGG pathway activation, and …

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Decoding Early Covid-19 Responses Using Mathematical Modeling Of Social Distancing Strategies Across Multiple Countries, Sri Gunturu, Suki Lewis, Katelyn Nguyen, Asma Azizi

Spora: A Journal of Biomathematics

During the early phase of the COVID-19 pandemic, before vaccines were available, countries implemented diverse combinations of social-distancing (SD) measures shaped by cultural norms and public acceptance. These differences produced varied outcomes in controlling viral spread, offering lessons for future health-crisis preparedness. We performed a reverse-engineering analysis of early COVID-19 case data from five socioculturally distinct countries—India, Vietnam, Italy, Finland, and the United States—selected to capture a range of initial prevalence levels. Using mathematical modeling and data fitting, we inferred the relative contributions of three SD interventions: face masking, quarantine, and isolation of infected individuals. We then employed an efficiency …

Inhomogeneous Branching Random Walks: Incorporating Genealogy And Density Effects, Lauren Ajax, Beatrice Durham, Pratima Hebbar, Cade Johnston, Jiayi Zhang

Spora: A Journal of Biomathematics

We introduce a novel framework using inhomogeneous branching random walks (BRWs) to model biological processes, specifically by introducing genealogy-dependence in branching rates and displacement distributions to model bacterial colony growth. Current stochastic models often either assume independent and identical behavior of individual agents or incorporate only spatiotemporal inhomogeneity, ignoring the effect of genealogy-based inhomogeneity on the long-time behavior of these processes. Such asymptotics are of independent mathematical interest and are crucial in understanding the emergence of patterns. We propose several inhomogeneous BRW models in 2D space where displacement distributions and branching rates vary with time, space, and genealogy. A combined …

Sheep Umbilical Cord Mesenchymal Stem Cells: Biological Characteristics, Ethical Considerations, And Translational Applications, Hasan M. Agha, Mohammed A. Abdalqader, Oh Chin Kin Michelle, Sabaa M. Agha, Jantson Hoh, Abdulmutalib Alabeed Allaq, Amjad Abdulhadi Mohammed, Muneer Mohammed Saleh Alsayadi

AUIQ Complementary Biological System

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their self-renewal capacity, multilineage differentiation potential, and paracrine activity. Limitations associated with the sourcing and scalability of human MSCs have increased interest in xenogeneic alternatives, particularly sheep umbilical cord–derived MSCs (sUC-MSCs). These cells display high proliferative capacity, stable karyotypes, and a typical MSC immunophenotype (CD44, CD73, CD90, CD105), with low basal immunogenicity. sUC-MSCs exhibit osteogenic, chondrogenic, and adipogenic differentiation potential and secrete angiogenic and immunomodulatory factors, including VEGF, HGF, IGF-1, TGF-β, and IL-10. Owing to their biological similarities to human MSCs and accessibility from perinatal tissue, …

Structural Characterization Of Peptide Nanoaggregates At Varying Concentrations And Their Impact On Cellular Responses, Malika Rozmetova

Theses and Dissertations

Peptide nano-assemblies can regulate cellular pathways in a structure-dependent manner. Here, we show that the enzyme-responsive peptide NapFFK(NBD)Yp forms distinct nanoscale assemblies at different concentrations, triggering differential ER stress and extracellular vesicle release in MDA-MB231 cells. These results highlight the importance of supramolecular organization in peptide–cell interactions.

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

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 …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Biol 225 - Laboratory Manual For Human Physiology, Corey Sullivan, Kristin Thurlby, Gwen Wright

Human Physiology

This laboratory manual for Human Physiology represents the Creative Commons licensed (CC-BY-NC 4.0) material created as an Open Educational Resource.

Investigating The Effects Of Nucleopore Defects On The Cellular Response To Stress In Als/Ftd Ipsc-Derived Neurons, Alicia Christine Collins

Open Access Dissertations

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a progressive neurodegenerative disease spectrum characterized by motor dysfunction, cognitive decline, and death within a few years of clinical onset. Hallmark features of ALS/FTD include defects in nucleocytoplasmic transport (NCT) and abnormal cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43, both of which have been shown to be exasperated by oxidative stress (OS). It remains unclear how these processes are connected and how they collectively contribute to neurodegeneration. To fill this gap of knowledge, we used human embryonic kidney cells, neuroblastoma cells, and induced pluripotent stem cell-derived cortical neurons harboring the ALS/FTD C9ORF72 …

A Deep Neural Approach To Network-Based Obfuscated Malware, Meera Parmar, Sunil Gautam

ASEAN Journal on Science and Technology for Development

The rising prevalence of obfuscated malware poses a critical threat to network security, undermining traditional detection methods and jeopardizing data integrity and system reliability in an increasingly connected world. This growing danger highlights the urgent need for advanced solutions to protect against evolving cyber risks. This research intro-duces a novel framework to enhance malware detection, employing a hybrid architecture that integrates spatial and temporal analysis with attention mechanisms. The approach leverages a large dataset subsample, focusing on key feature selection and augmentation to improve robustness against evasion techniques. This innovative framework offers a significant advancement in identifying malicious network traffic, …

When Words Flow Like Water: How The Enbridge Line 3 Pipeline Environmental Impact Statement Failed To Prevent Hydrogeologic Harm In Minnesota, Carly Gutzmann

Journal of Earth and Life Science

For the aquifers of Minnesota, the environmental impact statement (EIS) was a promise of protection that never left the page. An environmental impact statement is meant to be an aid in the decision making process in order to ensure that projects consider potential environmental harms that may occur. However, they are often used instead as another regulatory box to check, rather than as active considerations when planning. As such, a project plan can be flawed from the start—if project developers only consider environmental impacts after they have already put considerable time, effort, and funding into their project as-is, they may …

Mitochondria In Local Control Of Programmed Cell Killing & Resilience, Rashna Sharmin

Biology Dissertations - Archive

Specialized cells are commonplace and defined by different compartments. Organelle transport across cell compartments is critical for cell function, as in morphologically complex neurons. Specialized cells can undergo programmed elimination, an essential facet of normal development. My central thesis question asks how intracellular transport of mitochondria, the cell’s energy producers, regulate fated elimination of complex cells. I explored this using the specialized tail-spike cell (TSC) of the roundworm C. elegans. The TSC dies embryonically through the novel ‘tripartite’ developmental killing program, Compartmentalized Cell Elimination (CCE).  In my study, I defined and characterized events at the CCE initiation compartment of the …

Protecting Wetlands In The State Of Texas: Assessing Gaps In Regulations, Knowledge, And Professional Roles And Responsibilities, Grace A. Moy

Landscape Architecture Masters & Design Theses

Wetlands rank among earth's most productive ecosystems, providing crucial ecological services such as hydrological regulation, water purification, and habitat support (US EPA, 2015). In Texas, however, rapid urbanization, inconsistent policy enforcement, and the absence of statewide protection frameworks of hastened wetland degradation (Brody & Kang, 2011). Without a robust state regulatory framework (Environmental Law Institute [ELI], 2020), these ecosystems face increasing threats from development and hydrological disturbances.

This thesis aims to identify regulatory and knowledge deficiencies that influence Texas’ current wetland protection status and to offer targeted professional recommendations for landscape architecture professionals to address these shortcomings in future public …

The Ecological Consequences Of Horizontal Transmission Of Symbionts, Bibek Singh Parajuli

Biology Dissertations

Most multicellular organisms depend on their microbial symbionts for various functions, such as digestion, nutrient supplementation, pesticide degradation, and defense. While many insects acquire their symbionts vertically from their parents, thousands of species of true bugs (Hemiptera) across different families acquire their microbial symbiont, Caballeronia, from the environment each generation. Acquiring symbionts from the environment (horizontal transmission) has various ecological consequences for the host. In this study, I used the bug-Caballeronia model 1) to understand whether the free-living symbionts benefit from association with multicellular hosts, 2) to evaluate whether host specialization on symbiont strains varies across taxonomic levels, …

Effects Of Fermented Soybean Products On The Human Gut Microbiome, Microbial Metabolism, And Host Physiology, Shannon Moncier

Biology Dissertations

Fermented soybean products (FSPs) contain soybean-derived substrates, fermentation-associated microorganisms, and bioactive compounds that may interact with the human gut microbiome and host physiology. However, despite the growing interest in FSPs, longitudinal human studies specifically evaluating traditional Korean-FSPs (K-FSPs), particularly among United States-based populations, remain limited. The objective of this work was to evaluate the effects of three K-FSPs, including Cheonggukjang, Gochujang, and Doenjang, on host physiological responses, gut microbial community structure, predicted microbial functional potential, and fecal butyrate responses in healthy adults. Three independent dietary intervention cohorts were conducted using FSP formulations produced either by traditional artisan methods (Product A) …

Uncovering The Mechanism Of Reep2-Mediated Emt-Driven Membrane Trafficking In Lung Adenocarcinoma, Kevin Fulp

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking is frequently disrupted during cancer progression, and the underlying mechanisms remain largely unknown. Currently, no effective drugs target dysregulated membrane trafficking for cancer treatment. Recent evidence has demonstrated that epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma (LUAD) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression. To further dissect the pro-tumorigenic membrane trafficking program, we initiated an in vivo CRISPRi screen to assess more than 2,000 membrane trafficking-related genes in a syngeneic mouse LUAD model. We identified REEP2, an endoplasmic reticulum (ER) shaping protein, as a novel regulator of EMT-driven membrane trafficking. High REEP2 expression is …

Reep2-Driven Pro-Metastatic Secretion Promotes Lung Cancer Progression, Oluwafunminiyi E. Obaleye

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking plays a critical role in cellular function and is frequently dysregulated in cancer to promote metastasis. In lung adenocarcinoma (LUAD), the epithelial-to-mesenchymal transition (EMT) activating transcription factor, ZEB1, drives a pro-metastatic membrane trafficking program; however, the underlying molecular mechanisms remain poorly understood. Using a CRISPR interference (CRISPRi) in vivo screen of 2,099 membrane trafficking regulators in a syngeneic mouse model of EMT-driven LUAD, we identified REEP2 — an endoplasmic reticulum (ER) shaping protein — as a critical regulator of tumor progression. REEP2 mRNA expression correlates with poor prognosis, EMT signatures, and an immunosuppressive tumor microenvironment in LUAD patients. …

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 …

The Neuroprotective And Synergistic Effects Of Carbamoylated Erythropoietin And Insulin-Like Growth Factor-1 In Alzheimer's Disease, Morgan Jean Rothschadl

Dissertations and Theses

Alzheimer’s disease (AD) is a prominent neurodegenerative disease characterized by a decline in cognitive functioning. While current FDA-approved therapeutics exist, they fall short in creating significant and long-lasting improvements to cognition. A newer approach using neurotrophic factors has shown promising effects on improving cognition in clinical trials. Neurotrophic factors are secreted proteins that have multimodal effects in the brain, including supporting cell survival and functioning. Two neurotrophic factors of interest are carbamoylated erythropoietin (CEPO) and insulin-like growth factor-1 (IGF-1), and the goal of this study was to understand the synergistic and neuroprotective effects of CEPO and IGF-1 in AD. We …

Forage News [2026-02], University Of Kentucky

Forage News

No abstract provided.

The Presence Of Predators Moderates Evolutionary Responses Of Trinidadian Killifish To A Novel Parasite, Anne E. Christian

Biology Dissertations

The Healthy Herds Hypothesis suggests the idea that prey populations derive a benefit from their predators: predators reduce the exposure of their prey to infectious disease, both by limiting prey population densities and by eliminating sick individuals. Much research has focused on the balancing effect that predators have on ecosystems. There is a current need for research into whether these effects cause evolutionary shifts in prey populations, where strong predation pressure prevents prey species from evolving physiological tolerance or resistance to infectious agents. Parasites especially often have rapid effects on host evolution, due to exploitative interactions.

I seek to address …

The Effects Of A Thiamine Treatment On The Growth, Survival, And Foraging Behavior Of Thiamine-Deficient Michigan Lake Trout (Salvelinus Namaycush), Allie J. Muschong

Senior Honors Theses and Projects

The Great Lakes top predator Salvelinus namaycush (lake trout) suffers from Thiamine Deficiency Complex (TDC), which causes neurological problems and inhibits survival in young lake trout. The lake trout population in northern Lake Michigan experiences insufficient natural recruitment, necessitating yearly stocking. Few treatments have been explored, but preliminary studies in a hatchery setting suggest that increasing tissue thiamine promotes survival; thus, we expected a novel thiamine treatment to boost the foraging rate and weight of lake trout fry. We raised the eggs of six wild lake trout pairs, and applied treatments at both the egg stage and the hatch stage. …

A Phosphorylation Study Of Serine-8 And 26 In Two Fragments Of Amyloid Beta, A Peptide Involved In Alzheimer's Disease And Cancer, Colby J. Merrill

Senior Honors Theses and Projects

Both cancer and Alzheimer’s disease (AD) affect many people in the United States and impact the families of patients suffering from these challenging illnesses. Recently, it has been reported that these two diseases share several key pathophysiological features, and an inverse relationship exists between them. These diseases share several biochemical modulators, most notably the amyloid-beta protein, which affects tissues in both AD and cancer by misfolding and aggregating. Phosphorylation is believed to regulate the aggregation and toxicity of amyloid-beta by altering the protein's shape and charge, thereby changing its interactions with cells. Phosphorylation can also toggle some proteins on and …

Forage News [2026-03], University Of Kentucky

Forage News

No abstract provided.