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Articles 4621 - 4650 of 114105
Full-Text Articles in Entire DC Network
Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales
Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales
Thinking Matters Symposium
Mesoderm specific transcript (Mest) expression in white adipose tissue (WAT) is variable in genetically identical mice. Previous studies have shown a connection between Mest high expression and propensity for fat mass expansion. WAT and liver crosstalk has been well documented with hormone-like peptides signaling and regulating important metabolic pathways. The aim of this study is to investigate the correlation between these circulating factors and Mest expression in mice after exposure to a high fat diet (HFD). A group of 120 C57B6/J mice, males and females, were exposed to a HFD (Western Diet, 40 kcal% fat) for 4 weeks (8-12 weeks …
Oxycodone Self-Administration Modulates Ventral Pallidal Neuron Activity And Plasticity, Jessica Tooley
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
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 …
Microplastics In Brachyurans: Comparing Contents Of The Atlantic Ghost Crab, Ocypode Quadrata, And Their Surrounding Sediments, Michael See
Honors Theses
The emergence of microplastics as a threat to physiological and environmental health has led to an increase in studies in recent years that aim to identify and quantify potential risks to marine ecosystems. Ocypode quadrata is a species that is a critical component of coastal ecology, leading this study to collect and analyze specimens regarding microplastics and their presence as a pollutant to the marine environment. Samples were collected from beaches along the Grand Strand of South Carolina. Microplastic density and diversity were recorded from investigating fecal pellets from the captive crab specimens to examine microplastic abundance. In addition to …
Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud
Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud
Department of Orthopaedic Surgery Faculty Papers
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (AcanCreERT2; Sirt6fl/fl). Histological studies showed a degenerative phenotype in knockout mice …
Swine Solutions: Enhancing Ffa Supervised Agricultural Experience Projects, Hannah M. Daily, Dr. John Michael Mehaffey, Dr. Candis Scallan, Dr. Amy Mehaffey, Dr. Joe Mask
Swine Solutions: Enhancing Ffa Supervised Agricultural Experience Projects, Hannah M. Daily, Dr. John Michael Mehaffey, Dr. Candis Scallan, Dr. Amy Mehaffey, Dr. Joe Mask
Electronic Theses and Dissertations
Supervised Agricultural Experience (SAE) is a portion of the three-circle model of agriculture education, providing experiential learning opportunities for students. The immersion SAE encourages students to build upon foundational learning components in a real-world application. A popular area of the immersion SAE includes ownership of market swine being raised for exhibition. This study serves as a pilot mentorship program for agricultural science educators and students, creating an educational resource encouraging record-keeping techniques and skill development, leading to eventual independence from the student’s standpoint. The model for the Swine Solutions Program includes utilization of the provided handbook, completion of daily observation …
Evaluating Predictive Models For Predicting Total Score Of Beef Carcasses, Emmanuel Forson
Evaluating Predictive Models For Predicting Total Score Of Beef Carcasses, Emmanuel Forson
Electronic Theses and Dissertations
The beef industry plays a vital role in global agriculture, with carcass quality and consumer preference being key determinants of market success. This thesis examines predictive modeling techniques for estimating the Total Score of beef carcasses, a composite measure representing yield and quality, primarily used by the Nebraska Cattlemen Association. Using data from the Nebraska Cattlemen’s Foundation Retail Value Steer Challenge (2000–2023), the study compares the performance of First Order Multiple Linear Regression (MLR) with three machine learning techniques: K-Nearest Neighbors (KNN), Random Forest, and Gradient Boosting Machine (GBM).
The analysis focuses on six key predictors: Hot Carcass Weight, Back …
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
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
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
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, …
A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle
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 …
Depalmitoylation Regulates Metabolism And Mitochondrial Function, Sarah Lilly Speck
Depalmitoylation Regulates Metabolism And Mitochondrial Function, Sarah Lilly Speck
Arts & Sciences Graduate Student Theses and Dissertations
Tens of millions of Americans suffer from metabolic disorders, predisposing patients to cardiovascular disease, kidney disease, liver disease, infertility, and cancer. Unfortunately, the etiology of many of these diseases remains a mystery, limiting our ability to identify targets for pharmacologic therapies. Due to the relationship between altered lipid dynamics and metabolic dysfunction, we decided to study the effect of the posttranslational lipid modification, S-palmitoylation, on metabolism. S-palmitoylation is the only known reversible lipid modification for proteins, and this depalmitoylation process is catalyzed by acyl-protein thioesterases including APT1 and APT2. We hypothesized that APT deficiency in various tissues would predispose mammals …
Parental Guidance Suggested: Genetic, Epigenetic, And Environmental Factors Shape Allele-Specific Gene Regulation In Metabolic Traits, Celine Louise St. Pierre
Parental Guidance Suggested: Genetic, Epigenetic, And Environmental Factors Shape Allele-Specific Gene Regulation In Metabolic Traits, Celine Louise St. Pierre
Arts & Sciences Graduate Student Theses and Dissertations
Deciphering the “genotype to phenotype” map is a crucial goal of biology. We will not improve our ability to predict phenotypes from DNA sequences until we better incorporate epigenetic and environmental variation into our models of human health and disease. Genes are typically presumed to express both parental alleles equally, but genetic and epigenetic factors can cause one allele to function differently than the other (e.g. expressed or silenced more). These allele-specific imbalances can alter the final composition of a gene’s transcriptional product and ultimately shape phenotypes. Allele-specific effects have widespread impacts on complex traits, but how environmental signals contribute …
Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser
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
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 …
Demography Of Alligator Snapping Turtles (Macrochelys Temminckii) Along A Fishing Pressure Gradient, Luke T. Micek
Demography Of Alligator Snapping Turtles (Macrochelys Temminckii) Along A Fishing Pressure Gradient, Luke T. Micek
Electronic Theses and Dissertations
Passive fishing gear is a threat to the alligator snapping turtle (Macrochelys temminckii). The spatio-temporal persistence of this threat and its impacts on M. temminckii populations has not been quantified. I quantified the density of passive fishing gear and the demographic parameters of M. temminckii along a fishing pressure gradient in East Texas streams. Most gear was abandoned and illegally deployed, with densities varying seasonally. Detectability of passive fishing gear declined with increasing gear age, water depth, and volume, but increased with increasing precipitation. Macrochelys temminckii catch per unit effort, abundance, and survival was lower at sites with …
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
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 …
Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa
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 …
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
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.
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
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
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 …
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
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 …
Performative Biomechanics : Evolving Buildings Into Inhabitable Organisms, Josh Lopez
Performative Biomechanics : Evolving Buildings Into Inhabitable Organisms, Josh Lopez
Bachelor of Architecture Theses - 5th Year
There has always been a connection between biology and architecture. Michael Pawlyn, in Biomimicry in Architecture, coined “biomechanical designs” to describe structural techniques derived from creatures. This study investigates chitin-based creatures. Crustaceans, insects, and microscopic organisms all have exoskeletons in nature. With a focus on crabs, other crustaceans and bugs, this study examines and evaluates the formal characteristics of chitin-based organisms. The architectural creations of OXMAN, NOX, which was founded by Lars Spuybroek; and Lebbeus Woods are among those that are analyzed and studied due to their inspiration from living things. They follow functional effectiveness in nature, which is why …
Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han
Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han
Arts & Sciences Graduate Student Theses and Dissertations
Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for various hematological disorders. Umbilical cord blood (UCB) has emerged as an alternative source of hematopoietic stem and progenitor cells (HSPCs). However, the limited number of functional repopulating cells in UCB units has encouraged researchers to develop methods to expand them ex vivo. Hematopoiesis is strictly regulated by epigenetic modifiers. JARID2 is a co-factor of the Polycomb Repressive Complex 2 (PRC2), which recruits the complex to specific genomic loci and promotes the deposition of Histone 3 lysine 27 trimethylation (H3K27me3), a repressive epigenetic mark that mediates condensed chromatin packing to silence …
Progressive Multifocal Leukoencephalopathy In Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study, Michelly Abreu, Chirag B Patel, Krina Patel, Fareed Khawaja, Sudhakar Tummala
Progressive Multifocal Leukoencephalopathy In Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study, Michelly Abreu, Chirag B Patel, Krina Patel, Fareed Khawaja, Sudhakar Tummala
Faculty, Staff and Student Publications
Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy. CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to …
The Role Of Il-33 In Itch, Anna M. Trier
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. …
Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang
Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang
Faculty, Staff and Student Publications
Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.
Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …
Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel
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 …
Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks
Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks
Arts & Sciences Graduate Student Theses and Dissertations
Cardiovascular disease is the leading cause of death worldwide. A major treatment goal is to lower plasma lipids, especially low-density lipoprotein cholesterol (LDL), the cardinal risk factor for coronary artery disease (CAD). Patients with familial hypercholesterolemia (FH) experience early-onset CAD due to extremely high LDL. Underdiagnosis and undertreatment of FH are exacerbated by limited therapeutic options. However, one strategy has successfully lowered LDL in FH patients: Inhibition of the hepatically secreted protein Angiopoietin-like protein 3 (ANGPTL3). Despite promising clinical data, the mechanism by which ANGPTL3 inhibition lowers LDL has not been fully described. Although ANGPTL3 has been shown to modulate …
Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart
Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart
Arts & Sciences Graduate Student Theses and Dissertations
The neural crest is a transient, multipotent cell population unique to vertebrates that gives rise to diverse lineages, including craniofacial cartilage, peripheral neurons, glia, and pigment-producing melanocytes. Proper specification and differentiation of neural crest derivatives are orchestrated by tightly regulated gene regulatory networks, and disruption of these developmental programs can lead to congenital disorders and malignancies. Melanocytes, derived from the neural crest, are best known for their role in skin pigmentation but also contribute to homeostasis and specialized functions in the eye, ear, and heart. These cells produce melanin to protect tissues from ultraviolet radiation and oxidative damage, and they …