Cell and Developmental Biology Commons^™

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations and Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

Comprehensive Study Of Human Pathogenic Trypanosomatids: From Chemotherapies To Disease Ecology, Felipe Rodriguez

Open Access Theses & Dissertations

The vector-borne diseases Leishmaniasis and Chagas disease, caused by the kinetoplastid parasites Leishmania spp. and Trypanosoma cruzi respectively, are among the most important parasitic diseases in the group of neglected tropical diseases. Even though the two diseases are endemic to the Americas, they affect millions of people worldwide. Leishmaniasis and Chagas disease cause a great array of symptoms and some of them can be fatal if left undiagnosed and untreated. Current treatment regimens are becoming less effective, vaccines are still not available, and diagnosis needs to be improved. Vector control has been responsible for a decrease of diseases in endemic …

Role Of Sex Differences On Cancer Cachexia Progression And Fibrosis During Cancer Cachexia Development, Wesley Haynie

Graduate Theses and Dissertations

Cancer cachexia is a multifactorial wasting syndrome characterized by losses in bodymass >5% and occurs in approximately 80% of all cancer patients. Chronic inflammation and fibrosis play roles in cancer cachexia and a greater understanding of these contributing pathways to this pathology will pave the way for potential therapeutic avenues. While inflammation and fibrosis have been researched in various models of cancer cachexia, little to no studies have been performed in both sexes as most previous studies focus on males. PURPOSE The purpose of these studies is to investigate the role of fibrosis on cancer cachexia development as well as …

Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello

Graduate Theses and Dissertations

Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …

Exploring The Role Of Ampk In Nutrient Sensing And Signaling In The Human Parasite Trypanosoma Brucei, Jessica Jones

All Dissertations

African trypanosomes are protozoan parasites that cause the diseases African sleeping sickness and nagana, in humans and cattle respectively. These parasites have complex life cycles with infection of a mammalian host, ~5mM glucose, following transmission by an insect vector, essentially zero glucose. With these pathogens being exposed to rapidly changing glucose abundance in a host-dependent manner, the ability to sense and rapidly respond to changes in the availability of the hexose are critical. First, I provide a review of glucose metabolism in Trypanosoma brucei. Then, we explore the role of the catalytic α subunit of AMPK, a eukaryotic master …

Co-Option Of The Yolkless Oocyte Receptor For Crispr/Cas9 May Induce Transient Sterility In Female Drosophila Grimshawi Flies, Bronwyn Miller

LSU New Orleans Theses and Dissertations

Evolutionary developmental biology has historically used generalist model organisms like Drosophila melanogaster. The Hawaiian Drosophilidae radiation, which occurred just 25 million years ago, is an ideal lineage for work in Evo-Devo. Hawaiian flies make up 25% of the world’s Drosophila species and extreme diversity is seen throughout the group. D. grimshawi is a generalist Hawaiian picture-wing fly that has served as a model for the Hawaiian Drosophilidae radiation. However, D. grimshawi’s power and use as a model organism is constrained by our lack of ability to manipulate its genome. In this work, I attempted to edit the genome of …

Visualizing Anhydrobiosis: Liquid-Liquid Phase Separation, Membraneless Organelles, And Cellular Reorganization., Clinton J. Belott

Electronic Theses and Dissertations

Water is an integral and necessary component of life. It is then, exceedingly remarkable that some species are capable of surviving virtually complete water loss for extended periods of time. Several decades of intense research into anhydrobiosis, or life without water, have given significant insights into the molecular mechanisms governing this phenomenon. Anhydrobiosis-related intrinsically disordered (ARID) proteins have been demonstrated to be critically important for desiccation tolerance in many anhydrobiotic species and exhibit a considerably wide range of protective properties that include membrane stabilization, reinforcing bioglass formation, and protein stabilization. This dissertation begins with cellular dielectrophoresis suggesting that two ARID …

Longitudinal Monitoring Of Tumor Response To Immune Checkpoint Inhibitors Using Diffuse Optical Spectroscopy, Joel Isaac Rodriguez Troncoso

Graduate Theses and Dissertations

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in …

Differentiation Of Fetal Hematopoietic Stem Cells Requires Arid4b To Restrict Autocrine Kitlg/Kit-Src Signaling., In-Chi Young, Bogang Wu, Jaclyn Andricovich, Sung-Ting Chuang, Rong Li, Alexandros Tzatsos, Ray-Chang Wu, Mei-Yi Wu

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Oligomerization Of Mutant P53 R273h Is Not Required For Gain-Of-Function Chromatin Associated Activities, George K. Annor, Nour Elshabassy, Devon Lundine, Don-Gerard Conde, Gu Xiao, Viola Ellison, Jill Bargonetti

Publications and Research

The TP53 gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the C-terminal oligomerization domain (OD). These types of mutations are found in patients with the rare inherited cancer predisposition disorder called Li-Fraumeni syndrome. We previously found that mutant p53 (mtp53) R273H associates with replicating DNA and promotes the chromatin association of replication-associated proteins mini-chromosome maintenance 2 (MCM2), and poly ADP-ribose polymerase 1(PARP1). Herein, we created dual mutants in order to test if the oligomerization state of mtp53 R273H played a role in chromatin binding oncogenic gain-of-function (GOF) activities. …

(Non)Parallel Developmental Mechanisms In Vertebrate Appendage Reduction And Loss, Samantha Swank, Thomas Sanger, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Appendages have been reduced or lost hundreds of times during vertebrate evolution. This phenotypic convergence may be underlain by shared or different molecular mechanisms in distantly related vertebrate clades. To investigate, we reviewed the developmental and evolutionary literature of appendage reduction and loss in more than a dozen vertebrate genera from fish to mammals. We found that appendage reduction and loss was nearly always driven by modified gene expression as opposed to changes in coding sequences. Moreover, expression of the same genes was repeatedly modified across vertebrate taxa. However, the specific mechanisms by which expression was modified were rarely shared. …

Effect Of Estrogen Pretreatment On Glial-Like Cell Viability Following Stress Response Hormone Treatment, Bridget N. Smith, Kevin S. Burgess, Kathleen S. Hughes

Georgia Journal of Science

The role of steroid hormones is critical in cellular function. Previous studies have found a positive correlation between the endogenous estrogen 17β-estradiol and cellular protection. Conversely, exogenous conjugated equine estrogens provide less protective mechanisms than endogenous hormones, and little is known about the role of estrogens in cellular protection during a stress response. In the present study, we compare the effects of short-term estrogen pretreatments (alone and in combination) on cell viability when cells with glial cell morphology are exposed to either epinephrine or cortisol. Results showed that 1 µM 17β-estradiol resulted in decreased cell viability following the epinephrine treatment; …

Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess …

Chemoimmunotherapy Treatment Strategies On A Mathematical Model Of Cancer Evolution, Sandra M. Lopez, Yolocuauhtli Salazar, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Neural Network Controller Vs Pulse Control To Achieve Complete Eradication Of Cancer Cells In A Mathematical Model, Joel A. Quevedo, Sergio A. Puga, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Reconstructing Mathematical Models With Chaotic Attractors Via Genetic Algorithms, Luis A. Ramirez Islas, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Role Of Cpeb2 Alternative Splicing In Tnbc Metastasis, Shaun C. Stevens

USF Tampa Graduate Theses and Dissertations

Breast cancer is the second leading cause of cancer-related deaths for women in the U.S. Although the overall 5-year survival rate for breast cancer is 90%, this rate drops substantially for triple-negative breast cancer (TNBC) due to its high metastatic potential. Furthermore, there is a lack of targeted therapeutics for TNBC, and clinical trials have been largely unsuccessful. These characteristics validate the need for identifying novel therapeutic targets for the treatment of TNBC. The study of alternative splicing (AS) has emerged as a powerful tool to elucidate the molecular underpinnings driving cancer.

Our lab has identified cytoplasmic polyadenylation element-binding protein …

Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVB) containing six serotypes, B1–B6, affect various organs, and multiple serotypes can induce similar diseases such as myocarditis and pancreatitis. Yet, no vaccines are currently available to prevent these infections. Translationally, the derivation of vaccines that offer protection against multiple serotypes is highly desired. In that direction, we recently reported the generation of an attenuated strain of CVB3, termed Mt10, which completely protects against both myocarditis and pancreatitis induced by the homologous wild-type CVB3 strain. Here, we report that the Mt10 vaccine can induce cross-protection against multiple CVB serotypes as demonstrated with CVB4. We note that the …

Contact Normalization And The Role Of Maackia Amurensis Seed Lectin As A Novel Chemotherapeutic And Antiviral Agent, Stephanie A. Sheehan

Graduate School of Biomedical Sciences Theses and Dissertations

Cells communicate with each other to coordinate tissue function and homeostasis. Diseases including cancer, arthritis, and acute respiratory disease syndrome (ARDS) require a breakdown in this intercellular communication. For example, cancer progression is suppressed by junctional communication between nontransformed and transformed cells. This process is called contact normalization. Junctional communication must be disrupted to enable transformed cells to grow into malignancies. However, the junctions and mechanisms by which nontransformed cells normalize cell behavior have not been clearly defined. My project aimed to identify junctions and elucidate mechanisms underlying contact normalization. We discovered that cadherins, specifically N-cadherin, form junctions that enable …