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Articles 1 - 7 of 7
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam
Dissertations & Theses (Open Access)
ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …
Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj
Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj
Dissertations & Theses (Open Access)
Lung cancer is a highly aggressive disease responsible for ~25% of all cancer-related deaths, due in part to its proclivity to metastasize. Treating metastasis holds potential for improving patient survival but requires a deeper investigation into the underlying mechanisms. Some of these processes that can regulate metastasis are: (1) Oncogenic targets of epithelial micro-RNAs (miRNAs) are epigenetically de-repressed upon loss of the miRNAs during epithelial-to-mesenchymal transition (EMT) and in cancer. EMT confers plasticity and fitness to cancer cells promoting their survival through the metastatic cascade. This cascade and EMT are initiated by loss of the miRNA200 family (miR-200) and the …
An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan
An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan
Dissertations & Theses (Open Access)
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …
Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van
Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van
Dissertations & Theses (Open Access)
Plant Homeodomain Finger Protein 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known subunits of the Non-Specific Lethal (NSL) complex, which acetylates lysine residues on histone H4 and regulates gene expression. The current model assumes that PHF20 and PHF20L1 are present together in the NSL complex, although it has never been tested. Performing extensive biochemical analysis, we observed that PHF20 and PHF20L1 were exclusively and independently associated with the NSL complex. Our protein domain analysis showed that the C-termini of PHF20 and PHF20L1 are crucial for their interactions with the respective complexes. Furthermore, enrichment sites of PHF20 and …
Tissue-Specific Matrix Control Of Cell Cohesion And Migration Signaling Complexes, Tristen Tellman
Tissue-Specific Matrix Control Of Cell Cohesion And Migration Signaling Complexes, Tristen Tellman
Dissertations & Theses (Open Access)
The extracellular matrix (ECM) is a complex, interconnected network of three major constituents: collagens, glycoproteins, and proteoglycans, along with their enzyme modifiers. Within this network and beyond the structural role, each ECM molecule contributes a context-specific signal that influences cellular fate and behavior. Among these behaviors, cellular migration provides an essential function in developing tissues, wound healing, and cancer cell metastasis. Using two glandular organs, the normal salivary gland and the cancerous prostate, this dissertation describes the tissue-specific composition of two ECM signaling complexes (type I hemidesmosomes and the perlecan-semaphorin 3A-plexin A1-neuropilin-1 (PSPN) complex) and translates this knowledge into viable …
Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair
Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair
Dissertations & Theses (Open Access)
KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …