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Risk Factors For Icu Mortality In Patients With Hematological Malignancies: A Singlecenter, Retrospective Cohort Study From Turkey, Şahender Gülbi̇n Aygencel Bikmaz, Onur Gökçe, Meryem Merve Haşi̇moğlu, Nazlihan Boyaci, Melda Türkoğlu, Zeynep Arzu Yegi̇n, Zübeyde Nur Özkurt, Abdullah Münci̇ Yağci

Turkish Journal of Medical Sciences

Background/aim: Patients with hematological malignancies (HM) often require admission to the intensive care unit (ICU) due to organ failure, disease progression or treatment-related complications, and they generally have a poor prognosis. Therefore, understanding the factors affecting ICU mortality in HM patients is important. In this study, we aimed to identify the risk factors for ICU mortality in our critically ill HM patients. Materials and methods: We retrospectively reviewed the medical records of HM patients who were hospitalized in our medical ICU between January 1, 2010 and December 31, 2018. We recorded some parameters of these patients and compared these parameters …

Characteristics Of Children With Cat Sensitivity: A Prospective Cross-Sectional Study, Ezgi̇ Ulusoy Severcan, Nevzat Başkaya, Ayşegül Ertuğrul, Zeynep Şengül Emeksi̇z, İlknur Bostanci

Turkish Journal of Medical Sciences

Background/aim: Animal dander is one of the most common respiratory allergens in children, and there is evidence that cat sensitivity is a risk factor for asthma and allergic rhinitis. In this study, it was aimed to evaluate children with cat sensitivity and to identify their demographic and clinical characteristics. Materials and methods: Patients who were found to be sensitive to cats following skin prick tests performed in our allergy clinic over a period of one year (and two control groups), were included in the study. Patients in the study and control groups filled in a questionnaire including demographic and clinical …

Enhanced Central Sympathetic Tone Induces Heart Failure With Preserved Ejection Fraction (Hfpef) In Rats, Shyam S. Nandi, Kenichi Katsurada, Michael J. Moulton, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic …

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Investigating Novel Ispe Inhibitors Of The Mep Pathway In Mycobacterium, Seoung Ryoung Choi, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

In a recent effort to mitigate harm from human pathogens, many biosynthetic pathways have been extensively evaluated for their ability to inhibit pathogen growth and to determine drug targets. One of the important products/targets of such pathways is isopentenyl diphosphate. Isopentenyl diphosphate is the universal precursor of isoprenoids, which are essential for the normal functioning of microorganisms. In general, two biosynthetic pathways lead to the formation of isopentenyl diphosphate: (1) the mevalonate pathway in animals; and (2) the non-mevalonate or methylerythritol phosphate (MEP) in many bacteria, and some protozoa and plants. Because the MEP pathway is not found in mammalian …

Cortical Demyelination And Depression-Like Behavior Are Associated With Histaminergic Dysregulation In A Mouse Model Of Peripheral Inflammation, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Demyelinating diseases of the central nervous system are increasing in prevalence world-wide1,2 and manifest as motor, behavioral, and/or cognitive defects3 . The etiology and pathophysiology of demyelinating diseases remain unclear.

▪ We have previously observed cortical demyelination in our mouse model of non-anaphylactic cow’s milk allergy4 . The demyelination was associated with depression-like behaviors and region-specific increases in brain histamine and H3 receptor (H3R) levels4,5 .

❖ The brain’s central histaminergic system is tightly controlled and regulates many behaviors. Additionally, signaling through H3R plays a crucial role in oligodendrocyte differentiation, and thus, demyelination and remyelination6 .

▪ We hypothesized …

Prenatal Buprenorphine Exposure Reduces Expression Of Myelin Proteins In Neonatal Longs-Evans Rat, Christopher James Grahe

Theses, Dissertations and Capstones

In the USA and especially in WV, there has been a surge in the rise of opioid use disorder (OUD), and with it a rise in neonatal abstinence syndrome (NAS). What makes this rise in NAS so unfortunate is that the Medications for OUD (MOUD) do not prevent the development of NAS. Although the relationship between MOUD and NAS is still unclear, it is thought that buprenorphine, one of the main substances used to treat OUD in pregnant women, may feed into the development of NAS, which may affect mental and physiological development and cause other health problems. Via understanding …

An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks

Journal Articles: Pathology and Microbiology

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed …

Bacteria Commonly Associated With Central Nervous System Catheter Infections Elicit Distinct Csf Proteome Signatures, Matthew K. Beaver, Dragana Noe, Ishwor Thapa, Hesham Ali, Jessica Snowden, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

Background: Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long-term neurologic consequences including seizures, decreased intelligence quotient (IQ) and impaired school performance in children. Currently the diagnosis of shunt infection relies on bacterial culture; however, culture is not always accurate since these infections are frequently caused by bacteria capable of forming biofilms, such as Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa resulting in few planktonic bacteria detectable in the CSF. Therefore, there is a critical need to identify a …

The Antibacterial And Anti-Inflammatory Properties Of Probiotics Against Methicillin-Resistant Staphylococcus Aureus (Mrsa), Punploy Klawkla

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Dysbiosis refers to an imbalance in the types of microorganisms in a person’s natural f lora, associated with several diseases like asthma, type 2 diabetes, and atopic dermatitis (AD). Reports indicate that Staphylococcus aureuscolonizes about 60%-100% of AD skin, causing barrier dysfunction through virulence factors such as superantigens, enzymes, and other proteins. These factors disrupt skin homeostasis by affecting keratinocytes and immune cells. Additionally, dysbiosis in AD skin is marked by a reduction in commensal microbes like Staphylococcus epidermidis and Corynebacterium spp. In recent years, probiotics have been studied in both live bacteria and bacterial lysate forms. Most studies …

Elucidating The Impact Of Western Diet On Bone Marrow Cytokine Signatures: Understanding Poor Outcomes In Susceptibility To Infection And Progression Of Cancer, Lahari Kondeti

Theses, Dissertations and Capstones

Among other disease outcomes, obesity is associated with 1) reduction in long-lasting immune protection and 2) acquisition of cancer. Given our interest in hematopoietic stem and progenitor cell (HSPC) dynamics, we questioned if similar mechanisms in the bone marrow microenvironment contribute to obesity-induced HSPC alterations responsible for 1) decreased immune protection and 2) transformation of HSPCs in the pathogenesis of hematologic malignancies. The negative effects of obesity on immune protection are most notably established in influenza models. Influenza infection susceptibility is increased and influenza vaccine-induced immunity wains in obese individuals. Ongoing studies aim to define mechanisms for waning immunity at …

Recent Advances In Research And Management Of Human Monkeypox Virus: An Emerging Global Health Threat, Parveen Kumar, Benu Chaudhary, Nishant Yadav, Sushma Devi, Ashutosh Pareek, Sujatha Alla, Fnu Kajal, Behdin Nowrouzi-Kia, Vijay Kumar Chattu, Madan Mohan Gupta

Engineering Management & Systems Engineering Faculty Publications

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Review On Molecular Genetic Basis Of Hypertrophic Cardiomyopathy, Derek Pok Him Lee

Journal of the Hong Kong College of Cardiology

Hypertrophic cardiomyopathy (HCM) is one of the most common types of inherited cardiomyopathy with a wide range of clinical manifestations ranging from subtle myocardial hypertrophy to debilitating heart failure, cardiac arrhythmias, and sudden cardiac death. We reviewed the literature on the latest knowledge regarding the pathophysiology and molecular genetic basis of HCM. This will include laboratory studies on animal models and human pluripotent stem-cell derived cardiomyocytes and the theory of proximal mechanisms involving calcium handling and energy expenditure underlying HCM. The current review will also illustrate the pathogenicity of various associated genetic variants, genotype-phenotype correlation and the optimal approach to …

Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8, Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen

Journal Articles: Genetics, Cell Biology & Anatomy

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3^A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. …

Advances In Antimicrobial Peptide Discovery Via Machine Learning And Delivery Via Nanotechnology, Alexa Sowers, Guangshun Wang, Malcolm Xing, Bingyun Li

Journal Articles: Pathology and Microbiology

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used …

Integrating Comorbidity Knowledge For Alzheimer's Disease Drug Repurposing Using Multi-Task Graph Neural Network, Ko-Hong Lin, Kang-Lin Hsieh, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Alzheimer's Disease (AD) is a multifactorial disease that shares common etiologies with its multiple comorbidities, especially vascular diseases. To predict repurposable drugs for AD utilizing the relatively well-investigated comorbidities' knowledge, we proposed a multi-task graph neural network (GNN)-based pipeline that incorporates the corresponding biomedical interactome of these diseases with their genetic markers and effective therapeutics. Our pipeline can accurately capture the interactions and disease classification in the network. Next, we predicted drugs that might interact with the AD module by the node embedding similarity. Our candidates are mostly BBB permeable, and literature evidence showed their potential for treating AD pathologies, …

Transiently Impaired Endothelial Function During Thyroid Hormone Withdrawal In Differentiated Thyroid Cancer Patients, Li-Ying Hou, Xiao Li, Guo-Qiang Zhang, Chuang Xi, Chen-Tian Shen, Hong-Jun Song, Wen-Kun Bai, Zhong-Ling Qiu, Quan-Yong Luo

Faculty, Staff and Student Publications

PURPOSE: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.

METHODS: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the …

Survey Of West Nile And Banzi Viruses In Mosquitoes, South Africa, 2011-2018, Caitlin Macintyre, Milehna Mara Guarido, Megan Amy Riddin, Todd Johnson, Leo Braack, Maarten Schrama, Erin Gorsich, Antonio Paulo Gouveia Almeida, Marietjie Venter

Faculty, Staff and Student Publications

We collected >40,000 mosquitoes from 5 provinces in South Africa during 2011-2018 and screened for zoonotic flaviviruses. We detected West Nile virus in mosquitoes from conservation and periurban sites and potential new mosquito vectors; Banzi virus was rare. Our results suggest flavivirus transmission risks are increasing in South Africa.

Potential Mechanism Of 5-Ala Treatment Against Feline Infectious Peritonitis Virus Infection By Downstream Metabolite Ppix, Carissa V. Napier

Scripps Senior Theses

Feline coronavirus (FCoV) infection is ubiquitous in domestic cats, and up to 12% of FCoV-infected cats may succumb to Feline Infectious Peritonitis (FIP). FIP is a highly lethal infectious disease caused by FIP virus (FIPV), the virulent biotype of FCoV. It is difficult to properly diagnose FIP, and to this date, there is no effective FCoV vaccine nor licensed therapeutic for FIPV. Considering the threat FIP poses to feline health, there is a demand from both owners and veterinarians for a proper therapeutic to effectively treat the infection. 5-aminolevulinic acid (5-ALA) is a highly bioavailable amino acid that is naturally …

Association Of Notch3 With Elastic Fiber Dispersion In The Infrarenal Abdominal Aorta Of Cynomolgus Monkeys, Sohei Ito, Naofumi Amioka, Michael K. Franklin, Pengjun Wang, Ching-Ling Liang, Yuriko Katsumata, Lei Cai, Ryan E. Temel, Alan Daugherty, Hong S. Lu, Hisashi Sawada

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: The regional heterogeneity of vascular components and transcriptomes is an important determinant of aortic biology. This notion has been explored in multiple mouse studies. In the present study, we examined the regional heterogeneity of aortas in nonhuman primates.

METHODS: Aortic samples were harvested from the ascending, descending thoracic, suprarenal, and infrarenal regions of young control monkeys and adult monkeys with high fructose consumption for 3 years. The regional heterogeneity of aortic structure and transcriptomes was examined by histological and bulk RNA sequencing analyses, respectively.

RESULTS: Immunostaining of CD31 and αSMA (alpha-smooth muscle actin) revealed that endothelial and smooth muscle …

Relative Adrenal Insufficiency Is A Risk Factor And Endotype Of Sepsis - A Proof-Of- Concept Study To Support A Precision Medicine Approach To Guide Glucocorticoid Therapy For Sepsis, Chia-Hua Wu, Ling Guo, Dan Hao, Qian Wang, Xiang Ye, Misa Ito, Bin Huang, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Saha Cardiovascular Research Center Faculty Publications

Introduction: 25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether GC therapy should be based on the status of RAI are highly controversial. Our poor understanding about the pathogenesis of RAI and a lack of RAI animal model present significant barriers to address these critical issues.

Methods: Scavenger receptor BI (SR-BI) regulates stress-induced GC (iGC) production in response to stress. We generated SF1CreSR-BIfl/fl mice and utilized the mice as a RAI model to elucidate the pathogenesis of RAI and GC therapy in sepsis. …

Proteostasis & Neuroinflammation In Alzheimer's Disease, Christa C. Huber

Dissertations and Theses

Alzheimer’s Disease (AD) is a devastating disorder with no disease-modifying agent that stops or reverses the progression of the disease. Exosomes, 50 – 150 nanometers in diameter extracellular vesicles, play a role in intracellular communication and are currently being explored as a therapeutic agent in various diseases. In addition, exosomes possess favorable characteristics as a therapy; however, their low yield following isolation hinders their ability as a therapeutic agent. We exposed neuroprogenitor cells to heat shock (HS) before exosomes were isolated to explore the possibility of increasing exosome secretion. HS-derived exosomes exhibit significantly increased concentration and diameter compared to non-heat …

Lipids And Lipoproteins May Play A Role In The Neuropathology Of Alzheimer’S Disease, Omer Akyol, Sumeyya Akyol, Mei-Chuan Chou, Shioulan Chen, Ching-Kuan Liu, Salih Selek, Jair C Soares, Chu-Huang Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the …

Manipulation Of Components Of The Renin Angiotensin System In Renal Proximal Tubules Fails To Alter Atherosclerosis In Hypercholesterolemic Mice, Masayoshi Kukida, Naofumi Amioka, Dien Ye, Hui Chen, Jessica J. Moorleghen, Ching-Ling Liang, Deborah A. Howatt, Yuriko Katsumata, Motoko Yanagita, Hisashi Sawada, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Background and objective: Whole body manipulation of the renin-angiotensin system (RAS) consistently exerts profound effects on experimental atherosclerosis development. A deficit in the literature has been a lack of attention to the effects of sex. Also, based on data with gene-deleted mice, the site of RAS activity that influences lesion formation is at an unknown distant location. Since angiotensin (AngII) concentrations are high in kidney and the major components of the RAS are present in renal proximal tubule cells (PTCs), this study evaluated the role of the RAS in PTCs in atherosclerosis development.

Methods and results: Mice with an LDL …

Parental Instincts: The Neurological And Biological Factors Associated With Parenthood, Jared Reeder

Undergraduate Honors Theses

The following project involves a systematic review of the scientific literature on neural and biological changes of mothers and fathers in parenthood. Until very recently, little scientific research was devoted to studying how bearing children affects a man or woman’s long-term biology. Over the last twenty years, studies of neuroplastic changes in new mothers show specific neural mechanisms responsible for altering the behaviors of mothers during and after pregnancy. These changes in neuroplasticity alter behavior in such a way that led to mothers requiring less sleep and being more prone to hearing the cries of their children. In addition to …

Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang

All ETDs from UAB

Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …

Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde

All ETDs from UAB

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …

Investigating The Effects Of Immune Checkpoint Inhibition And Combined Treatment With Evofosfamide On The Tumor Microenvironment Through Hypoxia Imaging, Kaytlyn Carter Mcneal

All ETDs from UAB

Colorectal cancer (CRC) is a prevalent and deadly cancer worldwide. While immunotherapy, particularly immune checkpoint inhibition, shows promise in various cancers, its efficacy in CRC and other tumor types is limited. Hypoxia, characterized by inadequate tissue oxygenation, critically drives cancer progression, promoting tumor growth, metastasis, chemotherapy resistance, and poor prognosis. Evofosfamide, a hypoxia-activating prodrug, is being evaluated in clinical trials for combined use with checkpoint blockade as a potential therapeutic strategy. This study investigates the impact of hypoxia on immune checkpoint inhibition, evofosfamide, and combination therapy, while utilizing non-invasive molecular imaging to develop analytical methods for quantifying and characterizing tumor …

Molecular Determinants Of Retroviral Gag Targeting To The Plasma Membrane For Assembly, Dominik Herrmann

All ETDs from UAB

Human T-cell leukemia virus 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. Several serious diseases have been linked to HTLV-1 infection, such as Adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Between 10-20 million people are infected with HTLV-1 making it a major cause of morbidity and mortality worldwide. A comprehensive understanding of the factors that govern retroviral replication precludes the development of efficient antiretroviral therapies (ARTs). In the example of HIV-1, atomic level structural data was paramount to developing and improving upon many of the ARTs used today, underscoring the need for structure …