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Characterization Of The Plasma Proteome Of Nonhuman Primates During Ebola Virus Disease Or Melioidosis: A Host Response Comparison, Michael D. Ward, Ernst E. Brueggemann, Tara Kenny, Raven E. Reitstetter, Christopher R. Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C. Donnelly, Cary Retterer, Robert B. Norgren, Rekha G. Panchal, Travis K. Warren, Sina Bavari, Lisa H. Cazares

Journal Articles: Genetics, Cell Biology & Anatomy

Background: In-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host's immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus

Methods: Herein we report the quantitative proteomic analysis of plasma collected at various times of disease progression from 10 EBOV-infected and 5

Results: A total of 41 plasma proteins displayed significant alterations in abundance during EBOV …

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a …

Human-Like Nsg Mouse Glycoproteins Sialylation Pattern Changes The Phenotype Of Human Lymphocytes And Sensitivity To Hiv-1 Infection, Raghubendra S. Dagur, Amanda Branch-Woods, Saumi Mathews, Poonam S. Joshi, Rolen M. Quadros, Donald W. Harms, Yan Cheng, Shana M. Miles, Samuel J. Pirruccello, Channabasavaiah B. Gurumurthy, Santhi Gorantla, Larisa Y. Poluektova

Journal Articles: Munroe-Meyer Institute

BACKGROUND: The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins' chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known.

RESULTS: We mutated mouse …

Toward An Understanding Of The Clinical Relevance Of Nitric Oxide (No) Measurements In In Vitro Cell Culture Studies, Maria Paula Kwesiga

Dissertations, Master's Theses and Master's Reports

Diabetic foot ulcers (DFU) are one of the most challenging complications associated with diabetes mellitus (DM). Every 1 in 4 patients with DM are expected to develop an ulcer in their life time. The time course of healing is on average 90 to 120 days which increases the risks of infection, amputations and death. Nitric oxide (NO) is a signaling molecule produced in the body that has been established in the literature to serve many roles in the body, including as a vasodilator, neurotransmitter immune modulator and antimicrobial agent. Emerging evidence has shown that NO is indispensable in every stage …

The Microbiomes Of Pancreatic And Duodenum Tissue Overlap And Are Highly Subject Specific But Differ Between Pancreatic Cancer And Non-Cancer Subjects, Erika Del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from thirty-four organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Pancreas Of Coxsackievirus-Infected Dams And Their Challenged Pups: A Complex Issue, Sona Sarmirova, Maria Borsanyiova, Brigita Benkoova, Michaela Pospisilova, Rajkumar Rajasekaran, Katarina Berakova, Pavol Gomolcak, Jay Reddy, Shubhada Bopegamage

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had shown pancreatitis in challenged pups of CVB4-E2-infected dams. Present investigation describes the effect of gestational infection with this virus on the pancreas of both dams and their challenged pups. Gravid CD1 outbred mice were orally infected with CVB4-E2 virus at different gestation times. Pups were challenged orally with the same virus after 25 days of birth. Organs were collected at selected intervals postinfection (p.i.), and replicating virus and viral-RNA copies were analyzed. Additional readouts included histopathology …

The Role Of Isothiocyanates As Cancer Chemo‐Preventive, Chemo‐Therapeutic And Anti‐Melanoma Agents, Melina Mitsiogianni, Georgios Koutsidis, Nikos Mavroudis, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Vasilis Zoumpourlis, Tom Amery, Alex Galanis, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur‐containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemopreventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation …

Viral Emergence In Marine Mammals In The North Pacific May Be Linked To Arctic Sea Ice Reduction, Elizabeth Vanwormer, J. A.K. Mazet, A. Hall, V. A. Gill, P. L. Boveng, J. M. London, T. Gelatt, B. S. Fadely, M. E. Lander, J. Sterling, V. N. Burkanov, R. R. Ream, P. M. Brock, L. D. Rea, B. R. Smith, A. Jeffers, M. Henstock, M. J. Rehberg, K. A. Burek-Huntington, S. L. Crosby, J. A, Hammond, T. Goldstein

School of Veterinary and Biomedical Sciences: Faculty Publications

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from …

Factors Affecting Biofilm Formation In Oral Pathogenic Bacteria Of The Red Complex, Sidney Nechacov

Theses and Dissertations (Comprehensive)

Periodontal disease, also known as periodontitis, is a dental disease that is estimated to affect 2.4 billion people worldwide. This disease is characterized by chronic inflammation and bleeding of gums, as well as loss of tooth bone density. Currently, treatments for the disease include dental surgeries and various types of antibiotics, but few are targeted specifically at the Red Complex bacteria which are strongly associated with chronic periodontitis. The Red Complex consists of three bacteria: Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola. Each of these bacteria, are anaerobic oral pathogens that reside in the subgingival pocket adjacent to …

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …

Elevated Neutrophil To Lymphocyte Ratio As An Indicator Of Secondary Erythema Nodosum, A Retrospective Observational Study, Yildiz Hayran, Ayşe Öktem, Emi̇ne Buket Şahi̇n, Pinar İncel Uysal, Nuran Alli, Başak Yalçin

Turkish Journal of Medical Sciences

Background/aim: Erythema nodosum (EN) is an inflammatory disorder of subcutaneous tissue. Although etiopathogenesis of the disease is unknown, many predisposing factors such as infections, systemic disease, and drugs have been identified. Neutrophil to lymphocyte ratio (NLR) has been shown to be a novel inflammatory marker in many dermatological diseases. The aim of our study is to investigate NLR in EN patients and evaluate its relation to the underlying cause of the disease.Materials and methods: Between 2014 and 2018, clinical and laboratory data of 395 patients diagnosed with EN and 395 controls were extracted from patient files. EN patients were grouped …

Effects Of Different Percentages Of Body Weight-Supported Treadmill Training In Parkinson's Disease: A Double-Blind Randomized Controlled Trial, Tuğba Atan, Özden Özyemi̇şci̇ Taşkiran, Ayşe Bora Tokçaer, Gülçi̇n Kaymak Karataş, Asli Karakuş Çalişkan, Belgi̇n Karaoğlan

Turkish Journal of Medical Sciences

Background/aim: Body weight-supported treadmill training (BWSTT) might have greater effects than conventional treadmill training (TT) in neurological diseases such as Parkinson's disease (PD). The aim of this study was to evaluate the effects of different percentages of BWSTT on gait, balance, quality of life, and fatigue in PD.Materials and methods: Thirty-five patients with moderate to advanced PD were randomized into three BWSTT groups according to the supported percentage of body weight: 0% BWSTT (control group; unsupported TT), 10% BWSTT, or 20% BWSTT. Five patients were excluded due to early discharge and 30 patients completed BWSTT sessions lasting 30 min, 5 …

Kinesiophobia And Related Factors In Systemic Lupus Erythematosus Patients, Songül Bağlan Yentür, Sali̇ha Karatay, Deran Oskay, Abdurrahman Tufan, Hami̇t Küçük, Şemi̇nur Haznedaroğlu

Turkish Journal of Medical Sciences

Background/aim: This study was designed to investigate the relationship between kinesiophobia and the level of physical activity, depression, disease activity, fatigue, pain, and quality of life in female patients with systemic lupus erythematosus (SLE).Materials and methods: Seventy volunteer female patients were included in the study. Kinesiophobia, physical activity level, disease activity, fatigue, depression, pain, and quality of life were assessed using the Tampa Scale for Kinesiophobia (TSK), International Physical Activity Questionnaire- Short Form (IPAQ), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), McGill Pain Questionnaire- Short Form (MPQ-SF) and Nottingham Health Profile (NHP), …

Protective Effect Of Cyclosporine A In The Treatment Of Severe Hydronephrosis In A Rabbit Renal Pelvic Perfusion Model, Ben Zheng Zhou, Da Hu Zhang, Wei Min Yu, Jin Zhuo Ning

Turkish Journal of Medical Sciences

Background/aim: Cyclosporine A (CsA), a traditional immunosuppressive compound, has been reported to specifically prevent isch-emia reperfusion tissue injury via apoptosis pathway. This study aimed to explore the renoprotective effects of CsA on the kidneys of rabbits undergoing renal pelvic perfusion.Materials and methods: A total of 30 rabbits were randomly assigned into a control group (n = 6) and an experimental group (n = 24). The experimental group underwent a surgical procedure that induced severe hydronephrosis and was then stochastically divided into 4 groups (S1, S1?, S2, and S2?), consisting of 6 rabbits each. Groups S1 and S1? were perfused with …

Natural Product Induction In Pencillium And Human Caspase Crystallography, Kelly J. Mcgrath

Graduate Student Theses, Dissertations, & Professional Papers

No abstract provided.

Appropriately Timed Epigenetic Manipulation With Histone Deacetylase Inhibitors As A Platform Approach To Tumor Immunotherapy, Tyler Mccaw

All ETDs from UAB

In contrast to chemotherapy and radiotherapy, immunotherapy is able to respond in proportion to tumor burden and continue to evolve in parallel with the tumor mass and metastatic sites. In this way, immune-based cancer therapies are a living drug and hold enormous potential. In this work, we enforce expression of MHCII on a murine breast cancer model to study how changes in tumor biology can drive improved T cell-mediated responses. We next use histone deacetylase inhibitors to manipulate the microenvironment through a more clinically relevant, therapeutic approach. Herein, improvements in tumor control were driven by CD8 T cells and IFNγ, …

Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi

All ETDs from UAB

Ribosome biogenesis is one of the most central processes to cellular growth and metabolism. The synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I) is thought to be rate limiting for ribosome biogenesis, and is therefore subject to extensive regulation. The work presented in this dissertation characterizes two previously undiscovered pathways regulating rRNA synthesis. Due to the direct connection between ribosome biogenesis (and rRNA synthesis) and cellular proliferative potential, Pol I activity is upregulated in cancers. Cancer cells are hypersensitive to inhibition of Pol I, a quality that makes Pol I an attractive target for anticancer therapeutics. The …

Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu

All ETDs from UAB

The ability to quickly and accurately catalog an individual's genetic variation through genome sequencing has ignited a new era of diagnostic and therapeutic development for heritable disease. Although genome sequencing can provide a molecular diagnosis in a significant number of patients with suspected genetic disease, there remain a number of unsolved cases for which no pathogenic cause can be determined. This uncertainty can create a "diagnostic odyssey" in which sequential tests fail to provide a diagnostic resolution and can often delay beneficial treatment, impact family planning, and be emotionally challenging for patients and their families. Clearly, there is an unmet …

Dna Template Sequence Effects On Rna Polymerase I Transcription Elongation, Andrew Martin Clarke

All ETDs from UAB

The production of ribosomes represents the major synthetic effort of a rapidly dividing cell, and is intimately linked to the regulation of cell growth and proliferation. Developing a greater understanding of the mechanisms that regulate ribosome biogenesis is therefore crucial to understanding cellular control of the growth cycle. Ribosome biogenesis begins with the synthesis of the 35S ribosomal RNA (rRNA) by RNA polymerase I (Pol I). This RNA is co- and post-transcriptionally processed to produce the 18S, 5.8S, and 25S rRNAs. These RNAs are critical components of ribosomes, and Pol I has been demonstrated to be a key regulation target …

Novel Biomarkers For Parkinson Disease, Shijie Wang

All ETDs from UAB

Parkinson disease (PD) is the second most common neurodegenerative disorder with no reliable biochemical biomarkers for disease prediction or progression, nor disease-modifying treatments to slow the relentless progression. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known to increase LRRK2 kinase activity and increase the risk for late-onset PD. In this thesis, I discovered that LRRK2 is secreted into exosomes in urine and CSF, where LRRK2 kinase activity, reflected by autophosphorylation at pS1292 site, is preserved and reflective of cytosolic LRRK2 levels. In a cohort of biosamples from LRRK2 mutation carriers and matched controls, with and without PD, …

Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker

All ETDs from UAB

Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …

Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell

All ETDs from UAB

Drugs of abuse increase dopamine concentrations in the nucleus accumbens, a key reward structure that integrates contextual and cue-related information and regulates motivated behavior. This surge of dopamine triggers cell signaling cascades that converge in the nucleus to cause changes in gene expression, which are thought to lead to the observed functional and structural alterations in the reward circuit after exposure to drugs of abuse. However, while various drugs of abuse cause transcriptional changes, previously available tools have not had the capacity to deeply characterize these gene programs. Therefore, we optimized a dual lentivirus CRISPR system for targeted gene modulation …

Intracellular Compartment-Specific Abnormalities In Proteasome Expression And Activity In The Superior Temporal Gyrus In Schizophrenia, Madeline R. Scott

All ETDs from UAB

Protein homeostasis is an emerging component of schizophrenia (SZ) pathophysiology. Proteomic alterations in SZ are well-documented; however the underlying mechanism driving these changes remains unknown. The ubiquitin proteasome system (UPS) is fundamental to protein homeostasis regulation, and UPS transcript abnormalities in both blood and brain have been observed in SZ. Supporting a role for UPS dysfunction in SZ, we have reported decreased protein expression of ubiquitin-associated proteins in SZ brain. However, previous work on the proteasome has been limited to transcript expression. In the following studies we sought to address this gap in knowledge by characterizing proteasome dysfunction in the …