Life Sciences Commons^™

A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle

Arts & Sciences Graduate Student Theses and Dissertations

Pancreatic Ductal Adenocarcinoma (PDAC) is the most lethal solid malignancy with a 12% 5-year survival rate. Most tumors are detected at metastatic stages that are extremely resistant to therapy. PDAC recalcitrance is driven by a unique tumor microenvironment (TME) comprising dense collagenous fibrosis embedded with an abundance of cancer associated fibroblasts (CAFs) and infiltrating leukocytes. Preclinical studies have indicated that PDAC CAFs can have both pro- and anti-tumorigenic effects. This is likely owed to CAF phenotypic heterogeneity which was recently uncovered by single cell transcriptomics. Three major CAF subpopulations have been identified in mouse and human PDAC thus far: myofibroblastic …

Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser

Arts & Sciences Graduate Student Theses and Dissertations

The relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the Default Mode Network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. In this dissertation, I describe the development of a multisite in vivo electrophysiology pipeline for chronic …

Disrupting Nrf2-Driven Cancer Biology Through One-Carbon Metabolism Inhibition, Julius Chembo

Arts & Sciences Graduate Student Theses and Dissertations

Cancer remains a leading cause of mortality worldwide, with treatment resistance and recurrence posing major barriers to long-term survival. Despite advancements in targeted therapies, many cancers develop resistance to chemotherapy, radiation, and immunotherapy, significantly limiting their effectiveness. One key driver of therapeutic resistance is nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2), a transcription factor that regulates antioxidant responses and drug detoxification. While NRF2 protects normal cells from oxidative stress, its aberrant activation in cancer promotes tumor progression, metabolic reprogramming, and resistance to standard treatments. Alarmingly, NRF2 hyperactivation is implicated in some of the most aggressive and refractory malignancies, yet no …

Induced Cd8a Identifies Enhanced Human Nk Cell Il-15-Induced Proliferation And Metabolism And Modulates Nk Cell Activation, Celia Cubitt

Arts & Sciences Graduate Student Theses and Dissertations

Natural Killer (NK) cells are cytotoxic innate lymphoid cells that play an important role in the surveillance and elimination of virally-infected and malignantly-transformed cells. These primary effector functions are achieved by producing cytokines and chemokines which activate and recruit additional immune effectors, as well as direct cytotoxic killing via perforin and granzymes. NK cell function is tightly regulated by a balance of germ-line encoded activating, inhibitory, co-stimulatory, and cytokine receptors expressed at the cell surface. Through these activating and inhibitory receptors, NK cells recognize and kill targets without prior sensitization through the loss of self-identifying molecules such as major histocompatibility …

Mechanisms Of Mll-Rearranged Infant Leukemogenesis, Jonny Mendoza-Castrejon

Arts & Sciences Graduate Student Theses and Dissertations

Infant leukemias arise as either B cell acute lymphoblastic leukemia (B-ALL) or acute myeloid leukemia (AML) and are primarily driven by MLL/KMT2A-rearrangements (MLLr). Prior work has shown that MLLr transform fetal/neonatal hematopoietic progenitors more efficiently than adult progenitors. However, the genetics and epidemiology of MLLr leukemias present an important paradox. MLLr arise during late gestation under conditions that would seemingly favor leukemic transformation (i.e., fetal/neonatal progenitors have high proliferation rates and self-renewal). Furthermore, MLLr infant leukemias require very few cooperating mutations for transformation. Yet congenital leukemias are 10-fold less common than infant leukemias and >100-fold less common than childhood leukemias …

Expanding The Druggable Proteome By Integrating Deep Learning With Molecular Simulations To Predict Cryptic Pockets, Artur Meller

Arts & Sciences Graduate Student Theses and Dissertations

Of the protein structures deposited in the Protein Data Bank, less than half have pockets suitable for the binding of drugs. Even when proteins contain pockets in their ground state structures (e.g., the nucleotide-binding active site in myosin motors), achieving specificity remains a central challenge in drug design as many protein families share common structural motifs. Cryptic pockets are cavities absent in ligand-free experimental structures that form due to protein fluctuations in solution. They provide a means to specifically target proteins currently considered undruggable. While cryptic pockets are alluring drug targets, it remains difficult to predict which proteins will form …

Oxycodone Self-Administration Modulates Ventral Pallidal Neuron Activity And Plasticity, Jessica Tooley

Arts & Sciences Graduate Student Theses and Dissertations

Opioid use disorder is an urgent public health crisis in the United States. Over 800,000 Americans have died from opioid-related overdoses since 2000. Nearly 30% of people who misuse opioids begin with prescription oral opioids, such as oxycodone, and continue misusing to avoid the immediate aversive state of withdrawal and the persistent dysphoria associated with protracted abstinence from opioids. The persistency of these dysphoric symptoms increases the risk of relapse even after long periods of abstinence. Treatment for opioid use disorder currently consists of pharmacological opioid treatment to reduce withdrawal symptoms and behavioral counseling. However, these strategies have significant real-world …

Parapinopsin: A Photoswitchable Inhibitory Gpcr For Two-Photon Optogenetics, Bobbie J. Brown

Arts & Sciences Graduate Student Theses and Dissertations

The development of optogenetic tools has greatly advanced the capability of researchers to understand the connection between neuronal activity and behavior. Optogenetics makes use of opsins, which are light activated ion-channels, ion pumps, or G-Protein coupled receptor (GPCR-based) proteins used to regulate cellular activity. Coupled with technological advances in genetics and optical physics/microscopy, optogenetics can be used to control specific populations of cells in a time-locked, spatially specific manner. The experiments possible with optogenetics depend largely on the capabilities and limitations of the opsin used; thus, there have been continuous efforts to design and employ new opsins with a variety …

Monitoring Mangrove Dynamics And Evaluating Future Afforestation Potential In The Egyptian Red Sea, Rasha M. Abou Samra, Mansour Almazroui, Wenzhao Li, Hesham El-Askary

Mathematics, Physics, and Computer Science Faculty Articles and Research

Mangrove forests are vital for ecosystem services and coastal management but face stressors from anthropogenic activities and climate change. This study estimates the extent and afforestation potential of mangroves along the Egyptian Red Sea coast from 1984 to 2022 using NDVI derived from Landsat-5 and Sentinel-2 data in Google Earth Engine. Aboveground biomass (AGB), belowground biomass (BGB), carbon (C) stock, and CO₂ sequestration potential were evaluated using Sentinel-2 and elevation data. Future afforestation suitability (2020–2050) under SSP2-4.5 and SSP5-8.5 scenarios was assessed with the MaxEnt model. Mangrove area increased from 0.95 km² in 1984 to 1.46 km^{2 …}

Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like structured cell organelles functioning as cellular antennae with chemosensory and mechanosensory roles. Dysfunction of cilia results in ciliopathies, including renovascular diseases (polycystic kidneys, hypertension, aneurysm), mental impedances (Alzheimer's disease, Parkinson's disease, dementia), metabolic diseases (obesity, developmental skeleton defects), blindness, and so on. With a diameter of 150 nm, cilia can be cleaved, released and circulated in the body as injury biomarkers. We here assessed the potential use of isolated cilia as a novel delivery vehicle. Cilia were isolated from renal epithelial cells, and a specific-targeting chemotherapeutic was designed on the cilia. The data show a remarkable …

Metabolic Reprogramming Driven By Ant2 Deficiency Augments T Cell Function And Anti-Tumor Immunity In Mice, Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Amijai Saragovi, Ifat Abramovich, Bella Agranovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber, Michael Berger

Faculty, Staff and Student Publications

T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generate T cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding NAD+ regeneration. Interestingly, Ant2-/- naïve T cells exhibit enhanced activation, proliferation and effector functions compared to wild-type controls. Metabolic profiling reveals that these T cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Lastly, pharmacological inhibition of ANT …

Discovery Of Novel, Potent, And Orally Bioavailable Smarca2 Proteolysis-Targeting Chimeras With Synergistic Antitumor Activity In Combination With Kirsten Rat Sarcoma Viral Oncogene Homologue G12c Inhibitors, Sasikumar Kotagiri, Yawen Wang, Yanyan Han, Xiaobing Liang, Nicholas Blazanin, Hira Mazhar, Manu Sebastian, Phuong Kieu Nguyen, Yongying Jiang, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex, including SMARCA4 in nonsmall cell lung cancer with a frequency of up to 33% in advanced-stage disease, making it the most frequently mutated complex. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating that SMARCA2 is a high-value therapeutic target. Here, we disclose the discovery and characterization of potent, selective, and orally bioavailable cereblon-based SMARCA2 PROTACs. Biochemically, we showed that YDR1 and YD54 are potent SMARCA2 degraders. Further, we showed the antitumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

Enhanced Efficacy Of Ipilimumab Plus Nivolumab In Angiogenic Subtypes Of Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Herman Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

In metastatic clear-cell renal cell carcinoma (mccRCC), choosing between immuno-oncology (IO) combinations and IO plus anti-VEGF therapies is uncertain. The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5, which featured T-effector/cell-cycle signatures (p = 0.048). Complete responses were exclusively observed in cluster1/2 (p = 0.012), with longer progression-free survival (p = 0.014). Ipi/Nivo may particularly benefit angiogenic mccRCC, supporting molecular subtype-based treatment strategies.

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Phytosynthesis Of Magnetite Nanoparticles From Piper Betle (L.) Var. Mysore And Evaluation Of Anti-Microbial Properties, Ravikant Shekhar, Sushma T, Madhusudhan Mc, Prakash Hs, Geetha N

International Journal of Health and Allied Sciences

Background: Piper betle L., is a well-known herb in Asia, popular for its fragrance and mouth-refreshing properties. With more than 100 varieties, it has a number of medicinal and socio-economic benefits. Its phenolic constituents have been displayed to treat oral anaerobes, animate lipase action, and reduces lipid peroxidation. Magnetite nanoparticles, with their novel properties, are utilized in different applications, and amalgamating with plant sources, increases the efficacy of the nanoparticles to many folds.

Methods: In this study, biogenic synthesis of magnetite nanoparticles (MNPs) was carried out using aqueous solutions of Ferric Chloride and Ferrous Sulphate in a ratio of 2:1 …

Performance Of Lasso And Ridge Regression For Variable Selection In Genome-Wide Association Studies Of Maize Flowering Time, Dipok Deb

Data Science and Data Mining

Genome-Wide Association Studies (GWAS) are instrumental in identifying genetic variants linked to complex traits, providing valuable insights into trait heritability and biological mechanisms. This study applies GWAS to investigate flowering time in maize, a critical adaptive trait, using a diverse dataset of 5,000 recombinant inbred lines across eight environments. Traditional GWAS methods often encounter challenges in high-dimensional datasets due to the presence of multiple small-effect genetic loci. To address this, we compared two penalized regression methods—LASSO and Ridge regression—to perform variable selection and regression analysis within a GWAS framework. LASSO effectively reduced the number of predictors by selecting the most …

Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa

Karbala International Journal of Modern Science

The discovery of oncogenic BRAF mutations has prompted the development of inhibitors, yet resistance remains widespread. A more effective strategy involves targeting BRAF mRNA with siRNA to overcome resistance to BRAF inhibitors. This study aims to design potent siRNA for BRAF oncogene silencing using a computational approach. The full coding sequence of BRAF was retrieved from the NCBI database and potential siRNAs were predicted using the Ui-Tei, Reynolds, and Amarzguioui rules. Identified siRNAs were further analyzed using various prediction systems and parameters, including their interaction with the hAgo2 protein. The results identified that seven siRNAs (siRNA 23, siRNA 24, siRNA …

North Central Extension Risk Management Education Center, Part I: Helps Producers Manage Risks, Christine Lockert, Sheila Aikanathan Johnson, Bradley D. Lubben

Cornhusker Economics

Educating producers to manage risk and position their farm or ranch for future growth and success is the fundamental purpose of the Extension Risk Management Education (ERME) program.

The ERME program, funded by United States Department of Aagriculture’s National Institute of Food and Agriculture, provides training to help producers learn new strategies to manage complex and growing agricultural risks.

Established in 2001 and located at the University of Nebraska-Lincoln Agricultural Economics Department, the North Central Extension Risk Management Education Center (NCERMEC) has a long history of supporting risk management education programs serving producers in the region. NCERMEC, in conjunction …

Agreement Between Methods For Describing The Intensity Of A High Intensity Functional Training Workout, James W. Henley

Master's Theses

This study examined whether a speed-based metric, expressed as percent of maximal speed (%MS), could serve as a practical and accurate method for quantifying intensity in high-intensity functional training (HIFT). Traditional intensity markers—heart rate (HR), blood lactate concentration ([La-]), and rating of perceived exertion (RPE)—were compared to %MS during low- and high-volume (LV, HV) workouts using a combination of correlation and agreement analyses. Twelve males and twelve females completed a baseline assessment followed by two experimental workout sessions. Participants wore HR monitors, provided pre- and post-exercise [La-] samples and RPE scores, and performed maximal speed tests for each workout movement. …

Human Pain Neuroscience And The Next Generation Of Pain Therapeutics, Bryan A Copits, Michele Curatolo, Patrick M Dougherty, Robert W Gereau, Wenqin Luo, Maryann Martone, Hakan Olausson, Theodore J Price, William Renthal, Clifford J Woolf, Guoyan Zhao

Faculty, Staff and Student Publications

The recent approval of suzetrigine for acute pain treatment highlights both the success of targeting peripheral sensory neurons for pain management and the potential of developing new pain therapies primarily in human-based systems. To realize this transformative potential, further research into somatosensation and pain neuroimmunology in human systems is essential.

The Role Of The Cgas-Sting Sensing Pathway In Hiv-1 And Sars-Cov-2 Infections, Jenna Eve Eschbach

Arts & Sciences Graduate Student Theses and Dissertations

Human immunodeficiency virus type I (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the causative agents of two unique pandemics. For a successful replication cycle to occur, viruses need to strategically outmaneuver host cell defenses. The innate immune system is the first line of defense against viruses and other pathogens. Host pattern recognition receptors detect viral nucleic acids and initiate signaling cascades that culminate in the expression of interferon (IFN) and transcriptional upregulation of antiviral interferon-stimulated genes (ISGs). This dissertation examines the involvement of the innate immune response during early, post-entry steps of HIV-1 and SARS-CoV-2 infection. During …

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Graeme Segal, Stephanie Novak, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

Design, Implementation, And Reflection From An Interdisciplinary Course In Museum Studies, Brenna L. Decker

Journal on Empowering Teaching Excellence

Access the online Pressbooks version of this introduction here.

In Spring of 2023, I developed a special topics course titled Collection Material Handling to introduce students to museum management using Utah State University collections on the Logan, UT campus. The cross-listed upper-level course brought 16 USU students together from two disciplines: anthropology and natural sciences. The publication details how I used various learning theories to guide the creation of course content and how I structured and implemented activities in the classroom and in the collections. Examples of worksheets, activities, student feedback, and recommended improvements to assignments are provided. I encourage …

Physical Function In Young And Older Adult Active Pickleball Players – A Cross-Sectional Study, Leighanne T. Paulson, Eric Martin, Kent Adams, Marcus M. Lawrence

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 6: Issue 1, Article 5, 2025. Limited information exists on pickleball’s impact on physical function in older adults (65+ years), despite reported health benefits. PURPOSE: This cross-sectional study evaluated the physical function of active older adult (OA) women and men recreational pickleball players via handgrip strength (HGS) and fatigue (HGF), 6-minute walk distance (6MWD) test, as well as the short physical performance battery (SPPB) compared to sex-matched young adult (YA) controls. METHODS: Thirty YA (18-26 years; n=15 women/men) and 27 OA (65-89 years; n=13 women, n=15 men) participants who played pickleball …

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Anisa Turaeva, Nyla Walbrook, Andrea Feria, Rebecca Spokony

Publications and Research

In Drosophila melanogaster, hematopoiesis produces three types of blood cells (hemocytes): plasmatocytes, lamellocytes, and crystal cells, all of which provide vital immunological activities. Crystal cells have an especially essential role in melanization, a wound reaction mediated by prophenoloxidase enzymes. This study investigates genetic regulators of crystal cell growth by RNAi-mediated knockdown of five potential genes: ACXA, ACXB, Gp210, CG4390, and Cyp4s3. We used the GAL4/UAS system to selectively silence each gene and quantify crystal cell counts in wandering third instar larvae after heat shock-induced melanization. Our findings indicate that knockdown of ACXA and ACXB resulted in higher crystal cell …

Evaluating A Proprietary Tannin-Blend Product As An Alternative To Monensin And Tylosin Phosphate In Feedlot Cattle Diets, Luana D. Felizari, Luke K. Fuerniss, Jonathon L. Beckett, David S. Secrist, Guy D. Hufstedler, Bradley J. Johnson

Animal, Dairy, and Veterinary Science Faculty Publications

This study evaluates the effects of a proprietary tannin blend (BX), supplemented with or without sodium monensin (MON), on beef cattle performance, carcass traits, and health. Steers (n = 2986; initial shrunk body weight (SBW) 254 ± 9.2 kg) were allocated into 48 pens (61–62 steers/pen; 12 pens/treatment) fed for 230 d. Treatments included (1) no feed additives (CTL); (2) BX (7.95 g/animal daily); (3) MON + Tylosin phosphate (TYL; 437.52 mg MON/animal daily + 80 mg TYL/animal daily); or (4) MON+BX (437.52 mg MON/animal daily + 7.95 g BX/animal daily). Data were analyzed in R 4.2.1 using a …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H. Zhu, Talia M. Nir, Shayan Javid, Julio E. Villalón-Reina, Amanda L. Rodrigue, Lachlan T. Strike, Greig I. De Zubicaray, Katie L. Mcmahon, Margaret J. Wright, John Blangero

School of Medicine Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3–95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

The Role Of Il-33 In Itch, Anna M. Trier

Arts & Sciences Graduate Student Theses and Dissertations

Chronic itch is associated with a broad range of medical conditions, from inflammatory skin diseases to cancer and organ dysfunction, and has a lifetime prevalence of up to 20%. Despite being common and debilitating, the cellular and molecular mechanisms that drive chronic itch are just beginning to be elucidated. Thus, therapeutic options are limited. Recent studies have identified that various pro-inflammatory cytokines can directly activate sensory neurons. This has resulted in mounting interest in the therapeutic potential of inhibiting these neuro-immune interactions. IL-33 is constitutively expressed by epithelial cells, which allows for its rapid release upon tissue damage or stress. …

Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel

Arts & Sciences Graduate Student Theses and Dissertations

Type 2 diabetes (T2DM) is caused by the complex interaction of multiple genes and environmental factors. T2DM is characterized by hyperglycemia, insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β cell apoptosis rates are relatively low in diabetes. In this dissertation, I investigated β-cell failure in diabetes using KK and KKAy mouse models of polygenic T2DM, which spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. I found that β-cell failure in KK …