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Investigating The Thermodynamic Properties Of Fat10 And Fat10ylated Proteins, Aravind R

Theses and Dissertations

Degradation of proteins by the proteasome is crucial in regulating protein levels in the cell. Post-translational modifications, such as ubiquitylation and Fat10ylation, trigger proteasomal degradation of the substrate proteins. While ubiquitylation orchestrates multiple cellular processes, Fat10ylation is primarily involved in the inflammatory response. Unlike ubiquitin, recycled upon substrate degradation, Fat10 is degraded along with its substrate. Although the thermodynamic properties of the substrate are critical for effective proteasomal degradation, they remain poorly understood for the Fat10-proteasome pathway.

Here, we demonstrate that Fat10 exhibits markedly lower thermodynamic stability and faster unfolding kinetics compared to ubiquitin. This is due to the absence …

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

All ETDs from UAB

The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …

Editorial: Unveiling The Next Generation Of Cancer Immunity & Immunotherapy, Mohanraj Sadasivam, Nethaji Muniraj, Chellappagounder Thangavel

Center for Translational Medicine Faculty Papers

No abstract provided.

Restoring The AhupuaʻA: Community-Based Resource Management And Resilience In KauaʻI, Jeffrey W. Walbridge Jr.

Environmental Studies Senior Theses

This thesis analyzes Kauaʻi’s evolving resource management practices, examining the intersections of historical governance frameworks, modern legal systems, and indigenous knowledge. Utilizing the traditional ahupuaʻa system, Kauaʻi’s approach once promoted holistic stewardship across water, land, and energy resources. However, colonial policies, corporate influence, and economic pressures have gradually shifted this framework toward a market-driven model, often prioritizing tourism and development over ecological resilience. Key policy shifts as they fight to return to an ahupua'a based model – from the Great Mahele’s introduction of private land ownership to water diversions for plantation agriculture – help examine how these changes continue to …

Scproatlas: An Atlas Of Multiplexed Single-Cell Spatial Proteomics Imaging In Human Tissues, Tiangang Wang, Xuanmin Chen, Yujuan Han, Jiahao Yi, Xi Liu, Pora Kim, Liyu Huang, Kexin Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial proteomics can visualize and quantify protein expression profiles within tissues at single-cell resolution. Although spatial proteomics can only detect a limited number of proteins compared to spatial transcriptomics, it provides comprehensive spatial information with single-cell resolution. By studying the spatial distribution of cells, we can clearly obtain the spatial context within tissues at multiple scales. Spatial context includes the spatial composition of cell types, the distribution of functional structures, and the spatial communication between functional regions, all of which are crucial for the patterns of cellular distribution. Here, we constructed a comprehensive spatial proteomics functional annotation knowledgebase, scProAtlas (https://relab.xidian.edu.cn/scProAtlas/#/), …

Aspdb: An Integrative Knowledgebase Of Human Protein Isoforms From Experimental And Ai-Predicted Structures, Yuntao Yang, Himansu Kumar, Yuhan Xie, Zhao Li, Rongbin Li, Wenbo Chen, Chiamaka S Diala, Meer A Ali, Yi Xu, Albon Wu, Sayed-Rzgar Hosseini, Erfei Bi, Hongyu Zhao, Pora Kim, W Jim Zheng

Faculty, Staff and Student Publications

Alternative splicing is a crucial cellular process in eukaryotes, enabling the generation of multiple protein isoforms with diverse functions from a single gene. To better understand the impact of alternative splicing on protein structures, protein-protein interaction and human diseases, we developed ASpdb (https://biodataai.uth.edu/ASpdb/), a comprehensive database integrating experimentally determined structures and AlphaFold 2-predicted models for human protein isoforms. ASpdb includes over 3400 canonical isoforms, each represented by both experimentally resolved and predicted structures, and >7200 alternative isoforms with AlphaFold 2 predictions. In addition to detailed splicing events, 3D structures, sequence variations and functional annotations, ASpdb uniquely offers comparative analyses and …

Metsdb: A Knowledgebase Of Cancer Metastasis At Bulk, Single-Cell And Spatial Levels, Sijia Wu, Jiajin Zhang, Yanfei Wang, Xinyu Qin, Zhaocan Zhang, Zhennan Lu, Pora Kim, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

Cancer metastasis, the process by which tumour cells migrate and colonize distant organs from a primary site, is responsible for the majority of cancer-related deaths. Understanding the cellular and molecular mechanisms underlying this complex process is essential for developing effective metastasis prevention and therapy strategies. To this end, we systematically analysed 1786 bulk tissue samples from 13 cancer types, 988 463 single cells from 17 cancer types, and 40 252 spots from 45 spatial slides across 10 cancer types. The results of these analyses are compiled in the metsDB database, accessible at https://relab.xidian.edu.cn/metsDB/. This database provides insights into alterations in …

Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Grant Wang, Xiaona Liu, Aoqi Wang, Jianguo Wen, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing …

Opaque Ontology: Neuroimaging Classification Of Icd-10 Diagnostic Groups In The Uk Biobank, Ty Easley, Xiaoke Luo, Kayla Hannon, Petra Lenzini, Janine Bijsterbosch

2020-Current year OA Pubs

BACKGROUND: The use of machine learning to classify diagnostic cases versus controls defined based on diagnostic ontologies such as the International Classification of Diseases, Tenth Revision (ICD-10) from neuroimaging features is now commonplace across a wide range of diagnostic fields. However, transdiagnostic comparisons of such classifications are lacking. Such transdiagnostic comparisons are important to establish the specificity of classification models, set benchmarks, and assess the value of diagnostic ontologies.

RESULTS: We investigated case-control classification accuracy in 17 different ICD-10 diagnostic groups from Chapter V (mental and behavioral disorders) and Chapter VI (diseases of the nervous system) using data from the …

Plural Molecular And Cellular Mechanisms Of Pore Domain, Timothy J Abreo, Emma C Thompson, Anuraag Madabushi, Kristen L Park, Heun Soh, Nissi Varghese, Carlos G Vanoye, Kristen Springer, Jim Johnson, Scotty Sims, Zhigang Ji, Ana G Chavez, Miranda J Jankovic, Bereket Habte, Aamir R Zuberi, Cathleen M Lutz, Zhao Wang, Vaishnav Krishnan, Lisa Dudler, Stephanie Einsele-Scholz, Jeffrey L Noebels, Alfred L George, Atul Maheshwari, Anastasios Tzingounis, Edward C Cooper

Faculty, Staff and Students Publications

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. Kcnq2G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal …

The Latter-Day Saint Indian Placement Program: An Examination Through An Experiential Lens, Quinn Elise Christiansen

Theses and Dissertations

The Indian Placement Program, operated by the LDS Church from around 1947 to 2000, was influenced by the Church's belief in a connection between Native Americans to a Book of Mormon group known as the Lamanites. This group held a special status within the LDS Church because of their believed Israelite heritage as well as a prophecy promising their conversion in the last days. Spencer W. Kimball, motivated by both personal goals and his authority within the LDS Church, expanded on a successful experience of a young Native girl, Helen John, growing it into the broader Indian Placement Program. This …

The Manipulation Of Odor Availability Of Training Aids Used In Detection Canine Training, Katylynn B. Sloan, Michele N. Maughan, Caitlin E. Sharpes, Robin R. Greubel, Shawna F. Gallegos, Aleksandr E. Miklos, Lindsay D. Waldrop

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Detection canines can identify numerous substances for which they have been trained. Historically, and a point of ongoing contention, detection canine threshold (i.e., sensitivity or limit of detection) training has primarily focused on changing the weight of the training aid substance used. There has been minimal focus on other principles, such as surface area, confinement, and temperature, which can be manipulated to affect odor availability. That said, trainers have been manipulating odor availability for years without necessarily understanding the governing scientific principles. The aim of this review is to highlight the principles that control odor availability of a substance and …

Selectivity Of Invasive Species Suppression Efforts Influences Control Efficacy, Rae Fadlovich, Kevin Landom, Timothy E. Walsworth

Watershed Sciences Student Research

1. Highly fecund invaders and size-selective suppression efforts often limit the effectiveness of invasive species control programs, as compensatory processes can allow suppressed populations to recover. While population models have long explored how demographic characteristics impact management feasibility, there is a growing need to evaluate how the selectivity of suppression efforts might impact the long-term feasibility of control.
2. We use a simulation framework that integrates age-based selectivity to evaluate the effect of increasing the range of ages selected for during harvest-based invasive species control. We applied this approach to common carp in Utah Lake, the location of one of the world's …

Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher

All ETDs from UAB

A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …

Gendered Sexual Behaviors: Unintended Pregnancies, And Sexually-Transmitted Infections, Deirdre Ferguson

All ETDs from UAB

Education is the most effective way to address unintended pregnancies and sexually-transmitted infections (STIs). Education through preventative counseling has been negatively correlated with unintended pregnancies. Although research has shed light on the risks posing challenges to the prevention of unintended pregnancies, the consequential costs of these pregnancies continue to mount, both individually and societally. Birth control counseling corresponds with reducing the behavior of nonuse of contraceptives significantly. Education is thus associated with combatting inaccurate information passed along via primary social groups. To gain insight into the prevention of unintended pregnancies and STIs, data was gathered using a mixed-method approach incorporating …

Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul

All ETDs from UAB

RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

Perceptions And Preferences Of Virtual Health To Promote Exercise Among People With Physical Disabilities: An Exploratory Mixed Methods Study, Madison Mintz

All ETDs from UAB

People with physical disabilities and mobility limitations can greatly benefit from participating in a physically active lifestyle and adopting health-promoting strategies and behaviors. Benefits of physical activity include better sleep quality and quantity; decreased anxiety; weight loss or healthy weight maintenance; and maintained or increased balance, coordination, strength, and endurance, to name a few. However, rates of physical activity and exercise participation are disproportionate among people with disabilities (PWD). Current literature suggests a myriad of barriers and environmental inaccessibility as a leading cause of PWD not engaging or meeting physical activity guidelines. However, community-based, virtually-delivered programs have become dramatically available …

Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu

All ETDs from UAB

The regulation of gene expression in plant responses to drought has been thoroughly in-vestigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lack-ing. In this study, we report the use of single nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis deline-ated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly …

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …

Mammonc-Db: A Proteo-Genomic Platform For Comprehensive Breast Cancer Data Analysis, Integration And Visualization, Santhosh Kumar Karthikeyan

All ETDs from UAB

ABSTRACT In 2024, breast cancer (BCa) emerged as the most prevalent cancer among women, accounting for 15% of fatalities in the United States. BCa is a multifaceted disease characterized by various molecular alterations associated with tumor initiation, progression, and metastasis. Clinically, different treatments such as endocrine therapy, chemotherapy, and anti-HER2 therapy are employed based on the molecular subtypes of breast cancer. Despite initial treatment responses, some cases experience recurrence due to therapy resistance. The application of next-generation sequencing techniques and data analysis has significantly enhanced our understanding of BCa biology, including its initiation and progression. By exploring BCa multi-omics data, …

Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin

All ETDs from UAB

Pore forming toxins (PFTs) belonging to the ABC toxin complex (Tc) family are responsible for targeting and translocating toxins into target cells. ABC toxins consist of three separate subunits, each subunit providing a vital role in the cytotoxic mechanism of the Tc. The A subunit or TcA is the largest subunit of the complex and contains the binding domains and the translocation channel that perforates the membrane. The B subunit or TcB functions as a gated linker that forms a cocoon with the TcC which houses the toxic peptide and subsequently gets translocated through the TcB and TcA into the …

Elucidating The Impact Of Ribosome Biogenesis On Breast Cancer, Amr Rafat Elhamamsy

All ETDs from UAB

Ribosome biogenesis, a complex and multi-step process that occurs predominantly in the nucleolus, plays a critical role in cellular function by mediating protein synthesis through the assembly of ribosomal RNAs (rRNAs) and ribosomal proteins into functional ribosomes. In cancer, dysregulation of this process is linked to the development of specialized ribosomes (onco-ribosomes) that support oncogenic translation programs, enhancing tumor progression and therapeutic resistance. This dissertation explores the interplay between ribosome biogenesis and cancer, focusing particularly on the role of RNA Polymerase I (RNA Pol I) activity under hypoxic conditions and rRNA modifications in breast cancer. My first study elucidates the …

Humans Are Not Normal: How Did This Happen?, Hermann Strasser

Sociology Between the Gaps: Forgotten and Neglected Topics

No abstract provided.

Intouch Week Of January 6, 2025, New York Medical College

InTouch

• Celebrating the Best of 2024
• What Matters Most to Medical School Admissions Staff
• SHSP Adds Two Joint Degree Programs: Psy.D./M.P.H. and D.O./M.P.H.
• Pregnant Women with Pulmonary Arterial Hypertension Can Deliver Safely with Careful Management
• Love at NYMC

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

All ETDs from UAB

The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …

Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli

All ETDs from UAB

In nuclear medicine, theranostics utilizes radionuclide pairs for diagnosis and therapy. Radioscandium isotopes (43Sc, 44Sc, and 47Sc) offer a promising alternative to the 68Ga/177Lu theranostic pair due to their identical radiolabeling conditions, complexes and in vivo pharmacokinetics. 43Sc (t1/2=3.89h, β+=88%) and 44Sc (t1/2 =3.97h. β+=94.3%) are suitable for Positron Emission Tomography (PET) imaging whereas 47Sc (t1/2=3.3d. Eβ-ave=162keV) is suitable for targeted radiotherapy and Single Photon Emission Computed Tomography (SPECT). These isotopes require production routes that lead to high radionuclidic purity and radiochemistry development for incorporation into radiopharmaceuticals. This study explores the production, purification, and application of these isotopes. The proton …

Chronic Inflammation Compromises Natural Killer Cell Phenotype And Function In Myeloid Leukemia, Valeriya Kuznetsova

All ETDs from UAB

Chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) are blood malignancies characterized by clonal expansion and a compromised immune system. Tyrosine kinase inhibitors (TKI) revolutionized CML treatment; however, TKI discontinuation leads to relapses in half of the cases. Further, up to 10% of patients are TKI-resistant and develop a blast crisis resembling AML. Natural killer (NK) cells can clear malignant cells, representing a promising immunotherapy. However, NK cell activity is suppressed in leukemia, and the microenvironmental drivers of this impairment remain understudied. Despite this, the existing mouse models have not been tested to assess the effect of CML on …

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

All ETDs from UAB

Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …

Vitamin D Receptor Signaling Antagonizes RorT Signaling To Reprogram Th17 Cells, Blake Frey

All ETDs from UAB

Vitamin D3 has long been associated with protection against a myriad of autoimmune diseases commonly linked to dysregulation of the T helper 17 (Th17) program. Th17 cells rely on the nuclear receptor (NR) RORγt as the master transcription factor for differentiation and function, establishing a metastate that can drive pro-inflammatory or alternative pathways depending on external cues. Vitamin D3 signals through another NR, the vitamin D receptor (VDR), to inhibit IL-17A in favor of the immunosuppressive cytokine IL-10; however, the precise mechanisms remain unclear. We developed a novel dual Vdr reporter and conditional knockout mouse model, and for the first …