Cell and Developmental Biology Commons^™

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations and Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

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 …

The Role Of The Erbb Signaling Pathway In Cardiovascular Progenitor Cell-Based Repair, Christopher Ramos

Electronic Theses, Projects, and Dissertations

Adult mammalian hearts lack self-renewal and proliferative capabilities necessary for cardiovascular regeneration. Current treatments using cardiac progenitor cells (CPCs) for cell-based repair do not restore cardiac function in patients who experience a myocardial infarction (MI). Our laboratory has been studying Islet-1+ neonatal CPCs as a promising candidate for cell-based repair due to their ability to significantly improve cardiac function after MI in sheep. The current study addresses the hypothesis that the ERBB pathway is linked to the Hippo-pathway to activate YAP1 by the involvement of an autocrine loop that upregulates neuregulin (NRG). In our sheep model of MI and cardiovascular …

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 …

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

Dissertations and Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

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 …

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 …

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. …

Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz

Boise State University Theses and Dissertations

Integrity of the brain microvessels that form the blood-brain barrier (BBB) is maintained through fine-tuned regulation of endothelial tight junction proteins, chiefly represented by claudin 5 and the tight junction-associated MARVEL protein (TAMP) occludin. Under proinflammatory conditions in autoimmune-mediated multiple sclerosis (MS), autoreactive effector T cells are activated in white matter regions of the brain and spinal cord and release cytokines to recruit circulating neutrophils that, in turn, release neurotoxic substances. Lack of tight junctions in peripheral blood vessels allows neutrophils to exit blood vessels unhindered, but BBB tight junctions must first be downregulated before neutrophils can transmigrate into the …

Bicuspid Aortic Valve In Pregnancy Complicated By Aortic Valve Vegetation, Aortic Root Abscess, And Aortic Insufficiency, Shan He, Christopher A Huynh, Yi Deng, Sandeep Markan, Anvinh Nguyen

Faculty, Staff and Students Publications

A 39-year-old patient presented to our Labor and Delivery unit with fever and nausea in the context of recent bacteriuria. She was found to be in sepsis due to an incidental bicuspid aortic valve (BAV) complicated by aortic valvular vegetations, severe aortic insufficiency, and aortic root abscess, requiring an emergent cesarean section. Three days after delivery, the patient successfully underwent a mechanical aortic valve replacement and root reconstruction. In this case report, medical, surgical, and anesthetic management of parturient patients with BAV are discussed. The management of this congenital valvulopathy and vasculopathy is complicated by the extensive hemodynamic and cardiovascular …

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 …

Murine Trophoblast Stem Cells And Their Differentiated Cells Attenuate Zika Virus In Vitro By Reducing Glycosylation Of The Viral Envelope Protein, Biswas Neupane, Mona Fendereski, Farzana Nazneen, Yanlin Guo, Fengwei Bai

Faculty Publications

Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embryo deals with a viral infection. This study investigates ZIKV infection on mouse trophoblast stem cells (TSCs) and their in vitro differentiated TSCs (DTSCs), which resemble the cellular components of the trophectoderm layer of the blastocyst that later develops into the placenta. We demonstrate that TSCs and DTSCs are permissive to ZIKV infection; however, ZIKV propagated in TSCs and DTSCs exhibit substantially lower …

College Of Natural Sciences Scholarship Brunch Program, November 6th 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

This is the program for the first annual College of Natural Sciences Scholarship Brunch, held on November 6th, 2021 at McCrory Gardens.

College Of Natural Sciences Newsletter, November 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 11

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Media Coverage of CNS
Page 4 2021 Day of Scholars
Page 5 Astronomy Outreach
Page 6 SDSU Faculty & Students Host American Society for Microbiology Annual Conference
Page 7 Scholarship Brunch
Page 8 Open PRAIRIE Data, SI Final Exam Review Sessions
Page 9 Aamlid Family Anatomy Lab Photos

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K. Cleary, Matthew Silviera, Tobi J. Reidy, James Mccormick, Craig S. Johnson, Patricia Sylla, Jamie Cannon, Henry Lujan, Andrew Kassir, Ron Landmann, Wolfgang Gaertner, Edward Lee, Amir Bastawrous, Ovunc Bardakcioglu, Sushil Pandey, Vikram Attaluri

Department of Surgery Faculty Research

Background: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. Methods: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. Results: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …

Molecular Mechanism Of Action Of The Natural Polyphenolic Compound And The P300 Inhibitor “Carnosol” Against The Triple Negative Breast Cance, Halima Ali Mohammed Salem Alsamri

Dissertations

Carnosol, a naturally occurring Phyto polyphenol found in sage, oregano, and rosemary, has been extensively studied by our laboratory for its anticancer effects in various types of cancer. In human Triple-Negative Breast Cancer (TNBC), carnosol was shown to inhibit cellular viability, colony growth, induced cell cycle arrest, autophagy, and apoptosis. Nonetheless, very little is known about the molecular mechanism of action. In the current study, the ability of carnosol to inhibit metastasis and tumour growth was examined. Wound healing and invasion assays revealed that carnosol inhibited migration and invasion at non-cytotoxic concentrations of MDA-MB-231 cells. Also, carnosol was found to …

Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo

Publications and Research

Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …