Cell Biology Commons^™

Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola

Electronic Theses and Dissertations

Polyamines (PA) are ubiquitous in cells and highly involved in several important cellular functions and thus the dysregulation of their biosynthetic pathway is potentially associated with the progression of age-related diseases like Alzheimer’s’ disease (AD). Though there is research describing how PA content changes in organisms as they age or in those experiencing rapid aging from increased rates of senescence, as in Down syndrome (DS), it is not clear how this connection occurs and whether modulating this pathway may reveal downstream effects on related disease progression. This study examines how the modulation of the PA biosynthetic pathway by inhibition of …

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Srebp Versus Nrf1 Behavior Based On Cholesterol Sensing In Niemann-Pick Type C Using A Cos-7 Model, Christine Tran, Jacob Mcintyre, Felicity Sterling Phd

Science University Research Symposium (SURS)

Niemann-Pick disease type C (NPC) is a rare genetic disorder where cholesterol and lipid transport are blocked leading to accumulation in the lysosomes (National Organization of Rare Diseases (NORD), 2024; Boston Children’s Hospital). This accumulation can lead to neurological issues, such as developmental delay, ataxia, seizures, and early onset of dementia (Patterson, 2000). To study this disease more in depth, scientists have identified a drug called U18666A that induces NPC in the cells it is administered to (Lu, et al., 2015) which allows for the study of other structures and biomolecules in the sterol sensing and transport pathways.

Cholesterol has …

Advancing Crispr-Based Solutions For Covid-19 Diagnosis And Therapeutics, Roaa Hadi, Abhishek Poddar, Shivakuma Sonnaila, Venkata Suryanarayana Murthy Bhavaraju, Shilpi Agrawal

Chemistry & Biochemistry Faculty Publications and Presentations

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. …

The Role Of Siamese In G2 Checkpoint Regulation In Arabidopsis Thaliana, Martha A. Schwall

LSU Doctoral Dissertations

Cyclin-cyclin dependent kinase (Cyclin-CDK) pairs regulate progression through the checkpoints of the cell cycle. They bind with some specificity and must be bound to for their regulative properties to be active. The presence of cyclin-CDKs is conserved throughout eukaryotes, while differences in specifics exist between yeast, animals, and plants. In Arabidopsis, SIAMESE (SIM) is a CDK inhibitor that restricts progression through mitosis. Overexpression of SIM is required for endoreplication in Arabidopsis trichomes, and overexpression of SIM results in increased endoreplication in leaf epidermal cells. SIM is expressed at high levels in the root elongation zone, where it plays a …

Selective Pericyte Recruitment To Ec-Lined Tubes, Vessel Assembly Enhancement Through Pericyte Timp-3 Induction, And Pericyte Tbx2 In Capillary Formation And Maturation, Ksenia Marilyn Yrigoin Kaluguina

USF Tampa Graduate Theses and Dissertations

Capillaries, the smallest blood vascular networks, are formed by narrow and elongated endothelial cell (EC)-lined tubes with associated pericytes anchored to the abluminal tube surface. Our laboratory demonstrated that dynamic interactions between ECs and pericytes during capillary tube network assembly are required for basement membrane matrix deposition and maturation. We have also shown that key EC-derived factors promote pericyte recruitment, proliferation, and pericyte-induced basement membrane formation during capillary assembly. In the first section, we aim to identify if vascular smooth muscle cells (VSMCs) respond to the same factors and have the same invasive ability as pericytes since they are both …

Ferroptotic Cardiomyocytes Regulate Angiogenesis In The Regenerative Mouse Heart After Myocardial Infarction Through Direct And Indirect Mechanisms, Rebecca Ashley Stairley

MUSC Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of death in the United States, and heart attack occurs every 40 seconds in the US. A myocardial infarction (MI), or heart attack, results in ischemic injury and cardiomyocyte (CM) death. Mature mammalian CM renewal in the heart is insufficient to repopulate the lost tissue. However, the neonatal mouse heart retains its regenerative capacity through the first week of life, providing a valuable model to identifying regenerative factors.

Recent work by our lab revealed that the main mechanism of CM death in the heart post-MI is ferroptosis. In this study, we investigate the …

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

Denaturation Station: The Effect Of Guanidinium Chloride On Yeast Flocculation, Taylor Pulley, Jade Riddle, Angelina Scotece

Fall Showcase for Research and Creative Inquiry

Flocculation is a phenomenon found in yeast such as Saccharomyces cerevisiae in which cells aggregate in response to stressful environmental conditions. This occurs as the result of the interaction of flocculin proteins on the plasma membrane with mannose residues on the surface of other yeast cells which is often exploited in the brewing process to avoid expensive filtration steps. Guanidine is a chaotropic agent which reduces the stability of proteins by weakening the hydrophobic effect. Since it is believed that flocculation is dependent on protein-mannose binding interactions, if the structure of the flocculin proteins is altered by guanidine, their functionality …

Conditional Deletion Of Ceacam1 In Hepatic Stellate Cells Causes Their Activation, Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A. Van Grunsven, Scott L. Friedman, Robert F. Schwabe, Terry D. Hinds, Jr., Sivarajan Kumarasamy, Sonia M. Najjar

Markey Cancer Center Faculty Publications

Objectives: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARg on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation.

Methods: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre þ Cc1fl/fl mutants …

Development And Quantification Of An Attachment Assay For Epidermal Cells To Varying Extracellular Matrix Dilutions, Julian Vargas '26, Colleen L. Doçi

Annual Student Research Poster Session

The concept of cellular attachment is cells interacting with the extracellular matrices surrounding it. Extracellular matrices are made of various components, and it has been shown that the interactions differ between different classes of extracellular matrices. The basement membrane plays a critical role in the structure and function of the epidermis, the outermost layer of the skin. It is composed of key extracellular matrix components, which are crucial for structural stability of the skin and for maintaining the integrity of the epidermis. Through components like collagen, laminin, and proteoglycans, the BM facilitates communication between the epidermal cells and the connective …

The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall

Theses

Ewing’s sarcoma is an aggressive pediatric bone cancer that has low five-year survival rates, primarily due to metastatic disease and resistance of recurring tumors to traditional treatment options; therefore, novel treatment options are needed. The compound cannabidiol (CBD) has been shown to reduce cell viability, migration, and invasion in several tumor types, though the cellular mechanism of action is not well understood. Our lab has demonstrated the ability of CBD to reduce viability, migration, and invasion of Ewing’s sarcoma cells in vitro and is investigating differential protein and cytokine expression of known mediators of migration, such as intercellular adhesion molecule …

Identification Of Inflammatory Factors Contributing To Foaming In Atherosclerosis, Kavya Podila

Holster Scholar Projects

According to the National Institute of Health (NIH), atherosclerosis is attributed to the majority of cardiovascular disease (CVD) cases and is the leading cause of mortality in the US and worldwide. Despite significant medical advancements, the risk of cardiovascular events remains, warranting further mechanistic and pathogenic investigation. Advances in high-resolution omics profiling and the development of novel data-analytic bioinformatic tools previously enabled the novel discovery of two distinct programs in foaming, the central process in atherogenesis. The programs are pathogenic and homeostatic foaming, with the pathogenic foaming program being positively associated with disease. Using single-cell RNA sequencing (scRNA-seq) data from …

Effect Of Heat Stress On The Expression Of Circulating Cyto(Chemo)Kine And Inflammatory Markers In Broiler Chickens Selected For High- Or Low-Water Efficiency, Elizabeth S. Greene, Travis Tabler, Walter G. Bottje, Sara Orlowski, Sami Dridi

Poultry Science Faculty Publications and Presentations

Background:

Water scarcity is a current, significant global concern that will only increase under the pressure of climate change. Improving water efficiency of poultry is a new and promising area to help temper agriculture's future impact on fresh water availability. Here, we explored the effects of acute heat stress (HS) on circulating stress and inflammatory markers in 2 lines of broilers divergently selected for water efficiency. Methods:

Male chicks from low (LWE) and high water efficient (HWE) lines were raised in 12 environmental chambers (2 pens/chamber, 6 chambers/line, 20 birds/pen) under normal conditions until day 28. On day 29, birds …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring

Biomedical Sciences Theses & Dissertations

The dynamic cellular microenvironment, made up of resident cells and various macromolecules, differs markedly across tissues in the body. The multidirectional signals that cells receive from this microenvironment, along with the signaling they send back, heavily influence their physiology and behavior. Recent important findings have further validated this notion as the mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) driving changes in metabolic reprogramming and cancer fate redirection is understudied. The work presented in this dissertation focuses on exploring the impact of …

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …

Enhanced Bmp Signaling Via Alk2 In Osteoclasts Decreases Bone Density In Mice, Yolanda V. Gutierrez, Hiroyuki Yamaguchi, Yuji Mishina, Yoshihiro Komatsu

Research Colloquium

Bone remodeling is a complex biological process that has been extensively studied. Bone Morphogenetic Proteins (BMPs) are recognized as one of the critical growth factors that coordinate bone remodeling. Previous studies have demonstrated that BMP signaling in osteoclasts has a positive effect on osteoclast function. However, little is known about how each BMP type I receptors control osteoclastogenesis. To investigate this question, we utilized the Cre-LoxP system to specifically activate BMP signaling through ALK2 in mice. We utilized Cathepsin K (Ctsk)-Cre driver to activate BMP signaling in osteoclasts in mice. Compared with aged- and gender-matched controls, gain-of-function of BMP mutant …

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …