Cell and Developmental Biology Commons^™

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …

"Until There Is Nothing Left:" The Environmental And Social Impact Of Extractivist Industries In Grant County, New Mexico 1852-1999, Benjamin Shultz

Open Access Theses & Dissertations

This dissertation research expands and deepens our understanding of the environmental and social impact of the extractivist industries in Grant County, New Mexico, from 1852 to 1999. Much of the scholarship around mining in the historiography tends to focus on Arizona and Northern New Mexico, given the centralization of the mining industry in places like Taos and Santa Fe. The impact of the mining industry on the unique ecosystem and people who resided in Grant County, New Mexico, has not been as thoroughly researched by scholars. Thus, this dissertation extends the literature by revealing how the extractivist industries permanently changed …

Development Of A Behavioral Paradigm To Monitor Seizure Susceptibility And Severity In A Zebrafish Model Of Cblx Syndrome, Claudia Berenice Gil

Open Access Theses & Dissertations

Methylmalonic acidemia and homocysteinemia cblX type (cblX) (MIM#309541) is a rare, X-linked recessive disorder caused by a mutation in the HCFC1 gene. This disorder is characterized by multiple congenital anomalies which include intellectual disability, brain malformations, intractable epilepsy, microcephaly, and facial dysmorphia. The most severe symptom of cblX is intractable epilepsy which is 100% penetrant. Our lab developed a zebrafish model with a mutation in the zebrafish hcfc1a ortholog to study the mechanisms underlying seizure phenotypes in cblX. Our laboratory previously showed that mutation of hcfc1a results in increased number and proliferation of neural precursor cells (NPCs) and an increase …

Regulation Of Ccr7 Signaling Events By G-Protein-Coupled Receptor Kinases 2 And 3, Anahi Sanchez

Open Access Theses & Dissertations

G protein-coupled receptors (GPCR) can bind multiple ligands, leading to differential signaling events termed biased signaling. C-C chemokine receptor 7 (CCR7) is a GPCR known to have biased signaling between the two ligands it binds to, CCL19 and CCL21. Binding of C-C Chemokine Ligand 19 (CCL19) promotes a high level of CCR7 phosphorylation, while CCL21 leads to a much lower level of CCR7 phosphorylation; findings observed in HEK and dendritic cells. GPCR kinases (GRKs), which can control the phosphorylation patterns of a GPCR, are hypothesized to regulate biased signaling of a receptor. GRK expression differs between cell lines and cell …

Wired For Degradation: How Post-Translational Control Of Inducible Camp Early Repressor Protein Influences Melanoma Fate, Melissa Rose Spigelman

Theses, Dissertations and Culminating Projects

Melanoma is a highly aggressive form of skin cancer frequently driven by mutations in the BRAF gene, particularly the BRAFⱽ⁶⁰⁰ᴱ variant, which leads to sustained activation of the MAPK signaling cascade. Recent studies implicate the cyclic AMP (cAMP) signaling axis in melanoma progression and therapeutic resistance, highlighting the role of the Inducible cAMP Early Repressor (ICER), a transcriptional antagonist of CREB and CREM. ICER is downregulated during melanomagenesis and subject to post-translational regulation via phosphorylation and ubiquitin-mediated degradation. To investigate ICER’s functional relevance in vivo, e utilized a zebrafish melanoma model harboring brafⱽ⁶⁰⁰ᴱ, tp53−/−, and mitf−/−mutations, in which mitf expression …

Stromal Cells In The Small Intestine: Physiology, Localization, Function, And Alterations Induced By Chronic Arsenic Exposure, Scott Ventrello

All Dissertations

Arsenic is a prevalent toxicant found to affect around 94 to 240 million individuals in over fifty countries who are exposed to levels above the EPA and WHO standard of 10 ppb. As one of WHO’s top ten chemicals of public health concern, it is linked to several chronic diseases including diabetes, obesity, cancers, and inflammatory bowel diseases. Arsenic increases inflammation and disrupts the intestinal barrier in the small intestine and colon. Further, previous studies found that arsenic decreased secretory cell lineage and stromal cell gene expression markers in the small intestine. Thus, our goal was to investigate arsenic’s effect …

Investigating The Effect Of Fasting On Senescent Cells In Nothobranchius Furzeri Fish, Israel A. Akinola

Electronic Theses and Dissertations

Senescent cells (SCs) have been documented to accumulate with age in the organism. Recent studies have shown that reducing the number of SCs in an organism result in tissue rejuvenation and extension of life expectancy. Intermittent fasting is reported to have multiple health benefits and is speculated to reduce the burden of SCs. Nothobranchius furzeri are a new model organism for studying aging and for which there are short- and long-lived strains available. We hypothesize that long- and short-lived strains of N. furzeri will accumulate SCs at different rates; and that fasting will reduce the burden of SCs.

The results …

Thymosin Beta-4: A Novel Treatment For Acanthamoeba Keratitis, Victoria A. Murphey

All Theses

Acanthamoeba keratitis (AK) is a severe corneal infection caused by the free-living amoeba, Acanthamoeba. Both stages of its life cycle (trophozoite and cyst) cause infection, primarily in contact lens wearers. It is often misdiagnosed, leading to delayed treatment and poor clinical outcomes. Current treatment options for AK rely on anti-amoebic agents that are toxic to corneal epithelial cells. Further, no single drug can eliminate both forms of the amoeba. Approximately 30% of all AK infections require a corneal transplant.

Thymosin beta-4 (Tβ4) is a G-actin binding protein synthesized in almost all human cells, including corneal epithelial cells. Tβ4 exhibits …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Transcriptional Analysis Of Inflammatory Responses Of Mouse Trophoblast Stem Cells To Interferon Gamma, Arnaz Maryam Tariq

Honors Theses

The blastocyst faces significant immunological challenges during implantation, including heightened inflammation, which can contribute to implantation failure. Trophoblast stem cells (TSCs) and their differentiated forms (TSC-TBs), derived from the trophectoderm (TE) of the blastocyst, play a crucial role in immune modulation. Previous studies suggest that interferon-stimulated genes (ISGs) derived from TSC and TSC-TB provide antiviral protection to embryonic stem cells (ESCs). These findings show indication of a potential antiviral role for placental progenitors in shielding the blastocyst. Additionally, TSCs and TSC-TBs exhibit selectively attenuated immune responses to the proinflammatory cytokine interferon-gamma (IFN-γ) compared to mouse embryonic fibroblasts (MEFs). The attenuated …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Can A Ceh-27/Nkx2.1 Transgene Rescue Ceh-27 Neurodevelopmental Defects?, Meryl Gilmore, Martin L. Hudson

Symposium of Student Scholars

When the development of an organism’s nervous system is interrupted or altered, it can significantly impact that organism’s ability to survive and function properly. In our lab, we use a species of nematode called Caenorhabditis elegans as a model organism to characterize the roles of important transcription factors in human neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). Utilizing C. elegans makes analyzing this process in a lab very easy for many reasons; they are very small, have a rapid life cycle, invariant cell lineage, transparent bodies, and most importantly, around 80% of their genes have human orthologs. In …

Degradation Of Vascular Networks In A Huvec Model Of Dm1, Bonnie E. Butler

Departmental Honors & Graduate Capstone Projects

Myotonic dystrophy type 1 (DM1) is a genetic disease that causes muscle wasting and affects multiple organ systems. DM1 is caused by expanded CTG repeats in the 3’ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene (Harper, 2001). Skeletal muscle relies on capillaries for nutrient delivery and waste clearance (Olfert, 2016). Skeletal muscle and capillaries communicate via a variety of chemicals, including PDGF-BB which both skeletal muscle and endothelial cells secrete and have receptors for (Hamaguchi, 2023). Platelet derived growth factor receptor β (PDGFRβ), when bound to platelet derived growth factor BB (PDGF-BB), induces angiogenesis (Wang, 2012). In …

Bibliometric Analysis Of Research Trends Related To Human Immunodeficiency Virus., Madyson E. Johnson, Kaitlyn R. Coffman, Valerie Rivas, Elizabeth Barrett

ATU Scholars Symposium

Human immunodeficiency virus poses major health burden across the globe including the United States of America and has its zoonotic origin from the Simian Immunodeficiency viruses of sooty mangabey monkey and chimpanzee in Africa. Epidemiological trends indicate that even though the mortality rates for HIV are falling globally, the rates of new cases have been rising since 2010 in several countries including the USA. An estimated 0.5% of the human population is currently infected with the virus with countries like USA, India, Nigeria and South Africa carrying the highest burden of the disease. Host receptors such as CD4 and coreceptors …

Cloning The Yersinia Enterocolitica Alkaline Phosphatase For An Affinity Chromatography Ligand, Flavio E. Arellano

ATU Scholars Symposium

Alkaline phosphatase (ALP) is an enzyme responsible for the dephosphorylation of extra-cytoplasmic molecules. Conversion to a neutral molecule enhances their ability to pass through cell membranes. When microbes such as Yersinia enterocolitica are ingested, they are exposed to large changes in pH level. These changes range from ~pH6.5 in the oral cavity to pH 2 in the stomach and pH 8 in the mid-intestine. The ability of microorganisms to survive this change in pH it largely dependent on their ability to change which proteins are expressed at differing pH levels or their ability to modify those proteins to meet the …

Della Protein And Cbl-Cipk Signaling Pathway As Candidates For Genetic Engineering, Nathan F. Surles

ATU Scholars Symposium

No abstract provided.

The Effect Of Cellular Glucose Levels On Inotersen-Mediated Target Reduction In In Vitro Cell Models, Andrea Durwin

Honors Scholar Theses

Antisense oligonucleotide (ASO) drugs are a new therapeutic modality to treat rare as well as common diseases. These drugs work to reduce disease by targeting the mRNA of the gene that causes the disease, therefore limiting the proteins that further propagate the signs and symptoms of the disorder. Many people who suffer from more severe diseases, such as Alzheimer’s, Parkinson’s, Duchenne Muscular Dystrophy (DMD), and a wide array of cancers, utilize ASO drugs for treatment, but the drug is also used with those suffering from more common diseases such as diabetes. The efficacy of ASO drugs to silence their mRNA …

Mcf-7 Dense Breast Cancer Cells Modulate Stress Through Senescence, Lara Donadio, Moses Alfonso, Josiah Philip, Tyler Zatarain

Molloy Multidisciplinary Undergraduate Research Conference

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, with dense breast tissue being recognized as a significant risk factor for its development. This dense breast tissue, characterized by a higher concentration of mammary glandular tissue, represents additional sites for tumor development. The following study explores how the MCF-7 immortal cell line, representing dense breast cancer, modulates stress responses through cellular senescence. Cellular senescence is a defense mechanism that halts the cell cycle and acts as a tumor suppression mechanism, preventing out-of-control cell proliferation triggered by cytological stress. To simulate these stress conditions, we applied two agents: …

Enhancing Skin Cancer Literacy Amongst Young Adults: A Digital Design, Katherine Stoll

Honors Projects

The skin plays a vital role in protection, regulation, and homeostasis of the human body. Skin cancer, despite being mostly preventable, is one of the most common cancers. Young adults, ages 18 to 25, are vulnerable targets due to risky behaviors and misinformation regarding skin cancer. This project was designed by using digital media and website design to enhance skin cancer health literacy among young adults. Using a systematic literature review and research methods, an interactive website was designed to improve skin cancer health literacy and eliminate common misconceptions. The topics addressed throughout the website were the biological factors of …

Embryonic Stem Cell Research, Huda Abu-Suwa, Lisa K. Lashley, Charles J. Golden

Essays in Developmental Psychology

Stem cell research is a controversial issue that has received considerable attention over the last three decades. Stem cell research began in the early 1980’s, when stem cells were obtained from mice embryos and utilized to understand the functioning of stem cells (Grivennikov, 2008). In 1998, researchers discovered techniques for obtaining embryonic stem cells from human and growing them in laboratories. Since them, substantial research has been conducted on stem cells and their potential uses, which includes increasing our understanding of diseases and how they occur, treating various diseases, and testing new medications for safety and efficacy (Taylor, 2005).