Molecular Biology Commons^™

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu

USF Tampa Graduate Theses and Dissertations

Melanoma incidence and mortality rates are historically higher for men than women, with an estimated ~47% more new cases and twice the lethality in men in the US in 2023. Consistent with these discrepancies, emerging studies have highlighted the tumorigenic role of the male sex hormone androgen and its receptor (AR) in promoting melanoma aggressiveness. However, underlying cellular and molecular mechanisms and their precise pathological contributions are not well-defined. We recently discovered a sex-associated disparity in melanoma fucosylation, the post-translational modification of proteins with the dietary sugar L-fucose. Fucosylation, the conjugation of fucose moieties onto different glycan linkages on target …

Long Non-Coding Rna As A Potential Diagnostic Tool In Coronary Artery Diseases - A Systematic Review, Arthi Sri A.S, Vishnu Priya Veeraraghavan

Annual Research Symposium

POSTER - SYSTEMATIC REVIEW - LONG NON CODING RNAS AS DIAGNOSTIC MARKER FOR CAD

Correlation Between Salivary Levels And Tissue Expression Status Of Her2 In Breast Cancer Patients - A Cross-Sectional Study, Arthi Sri A.S, Massillamani F, Vinothkumar Thilla Sekar

Annual Research Symposium

The study aims to investigate if soluble salivary human epidermal growth factor receptor-2 (HER2) would play a role in the diagnosis of breast cancer patients and also to find out the influence of demographic and hormonal factors on the salivary HER2 levels in breast cancer.

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …

Cold-Inducible Rna Binding Protein Impedes Breast Tumor Growth In The Pymt Murine Model For Breast Cancer, Daniel A. Lujan, Joey L. Ochoa, Ellen J. Beswick, Tamara A. Howard, Helen J. Hathaway, Nora I. Perrone-Bizzozero, Rebecca S. Hartley

Markey Cancer Center Faculty Publications

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse …

Studying The Genes And Conditions That Influence Root Development, Tessa Holtkamp, Hannah Ordonez Webb

Undergraduate Research Symposium

Root development in plants is essential for their survival and understanding how hormones influence their development can explain how plants grow under different circumstances. Researching how Indole-3-butyric acid (IBA), a hormone that induces root production, affects the plant model Arabidopsis thaliana helps explain the hormone's effect in agricultural crop systems. To understand root pathways, we performed assays on mutant lines of Arabidopsis by growing plants on varying concentrations of IBA. For wild-type and mutant lines, phenotyping experiments like branching of roots, lengths of stems, and root length were conducted along with PCR and restriction digest genotyping experiments to compare their …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Identification Of Regulatory Elements In The Untranslated Regions Of Streptolysin S Associated Gene A Messenger Rna From Group A Streptococcus, Cameron R. Carroll, Sara G. Nibar, Alexis S. Brown, Lauren R. Angello, Gabriela C. Pérez-Alvarado, Brian M. Lee

Journal of the South Carolina Academy of Science

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a human pathogen associated with a variety of diseases such as strep throat, scarlet fever, toxic shock syndrome, and necrotizing fasciitis. One of the virulence factors released by GAS during an invasive infection is a cytotoxic peptide, streptolysin S (SLS), which inhibits the immune response to necrotizing fasciitis. The streptolysin S associated gene A product, SagA, is modified to produce SLS. Thesag operon includes sagA and the genes required for enzyme-mediated post-translational modifications of SagA and the export of SLS. The sagA gene is contained within the pleiotropic …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira Makarova, Eugene V Koonin, Satish Nair, Shunsuke Tagami, Konstantin Severinov, Maria Sokolova

Department of Biochemistry and Molecular Biology Faculty Papers

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Lipid Genetics In Pregnant Women: Maneuvering The Challenges Of Using Degraded Samples, Kylee Meece

Mahurin Honors College Capstone Experience/Thesis Projects

The results of this project will explore a novel approach to lipid metabolism in pregnant women by exploring the relationship between maternal gene expression of genes critical for fat metabolism, protein expression, and maternal and neonatal outcomes. The study will also examine gene expression in lean pregnant women compared to obese pregnant women, shedding light into the adverse pathology of obesity during pregnancy. These findings may uncover a mechanism related to gene-expression that connects unfavorable maternal fat metabolism to inflammation and/or insulin resistance, which may help to uncover future targets for interventions.

The analysis of lipid gene expression requires the …

Thymidine Phosphorylase Is A Promising Target In Sars-Cov-2 Spike Protein-Enhanced Thrombosis, Renat Roytenberg

Theses, Dissertations and Capstones

Thrombosis, as an underlying mechanism in cardiovascular diseases, is the leading global cause of death in the 21st century. Infection is a risk factor for thrombosis, and the coronavirus disease 2019 (COVID-19) pandemic has led to a rise in the incidence of thrombosis, thereby increasing mortality. In comparison to previous severe coronavirus outbreaks, rates of thrombosis in COVID-19 have been unprecedented. COVID-19 is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein (SP), the key used to enter host cells, is implicated in thrombosis pathology, though mechanisms are not fully understood. The SARS-CoV-2 …

Assessing The Role Of Kmt2b Knockdown In Rhabdoid Tumorigenesis Utilizing Crispri, Karah Edmonds, Andrea Florian Phd

Science University Research Symposium (SURS)

An aggressive blood cancer commonly observed in pediatric patients, Mixed Lineage Leukemia (MLL), has a regulatory MLL complex that promotes histone methyltransferation. Modifying histones utilizing histone methyltransferases like KMT2B (MLL2), is essential for gene expression by regulating transcription. Loss of function and inhibition of KMT2B leads to dysregulation of transcription and therefore promotes MLL tumorigenesis. To improve cancer-targeted therapies, we will use CRISPR interference (CRISPRi) to knock down the expression of KMT2B and measure levels of Rhabdoid tumor cell proliferation and apoptosis. Previous research surrounding the MLL complex suggests that decreased expression of KMT2B will lead to increased levels of …

Analysis Of Protein-Protein Interactions Between Legionella Pneumophilia Effectors, Briana Harness

Mahurin Honors College Capstone Experience/Thesis Projects

Legionella pneumophila an intracellular, opportunistic pathogen that is the causative agent of Legionnaires’ disease and Pontiac fever. A key component of Legionella’s pathogenicity is a series of effector proteins, which aid in the establishment of the Legionella-containing vacuole (LCV). The abundant library of effector proteins L. pneumophila has within its arsenal gives L. pneumophila the ability to infect several different hosts. The pathogenesis of L. pneumophila within various hosts depends on its ability to modulate the activity of its effector proteins through protein-protein interactions within effectors and eukaryotic host cell proteins. By understanding how L. pneumophila regulates its effectors, a …

Detecting Interactions Between Mps3 In Linc Complex And Ndj1 In Nuclear Pore Complex In Mechanically Stressed Yeast, Dean Boecher, Rebecca Adams

[Archive] Belmont University Research Symposium (BURS)

The mechanisms of how mechanical stress is translated into cellular action and structural reorganization within the nuclear envelope are largely unexplored. The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a transmembrane protein complex that connects the actin cytoskeleton to the lamin nucleoskeleton, enabling mechanical forces to be translated between the cytoplasm and the nucleus. A better understanding of the translation of physical forces into cell responses can be gained through confirming the existence of interactions between LINC complex proteins and nuclear pore complexes (NPCs), which control the exchange of biochemical signals and macromolecules in and out of the nucleus …

Long-Read Mdm4 Isoform Sequencing Reveals Aberrant Isoform Landscape In Metastatic Melanomas, Nehaal Rooha Patrick

Browse all Theses and Dissertations

The changes in splicing of MDM4 in human melanomagenesis are critical to p53 activity and represent potential therapeutic targets. Genomic characteristics of melanoma and precursor lesions, such as copy number variation and gene expression, have been investigated in detail. However, there has never been a detailed survey of splicing changes that occur during melanomagenesis. Splicing changes can be a very early event in melanoma tumor progression, with characteristic changes in the p53 pathway already in place in early nevi. MDM4 is upregulated in a strong majority of melanoma cases and has been described as a “key therapeutic target in cutaneous …

Microbial Prevalence And Antibiotic Resistance Associated With Urban Food Production Systems, Nirosha Ruwani Amarasekara

Wayne State University Dissertations

Despite the increasing popularity of urban agriculture and farmers’ markets, there is a lack of scientific data on microbial prevalence and antibiotic resistance associated with this unique food production system. The overall goal of this research is to understand antibiotic resistance and microbial prevalence in soil and fresh produce associated with urban agriculture. Specifically, we aim to investigate ARG in association with resistance genes to metals and other compounds in urban agricultural soil as well as antibiotic resistome and Listeria contamination in fresh produce distributed in urban communities.

In the initial phase of this research, soil samples were collected from …

The Role Of Uchl1 In Skeletal Muscle Development And Regeneration, Ryan Antony

Dissertations and Theses

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally discovered in neurons. UCHL1 is also expressed in skeletal muscle, but its functions remain to be fully understood. Myogenesis is a critical process involved in embryonic development, growth, and regeneration following injury. Skeletal muscle injury is prevalent in trauma and surgical procedures, and skeletal muscle ischemia-reperfusion (IR) injury is a common yet dangerous public health problem. Here we reported that UCHL1 negatively affects muscle growth during aging as well as the regeneration process following IR injury. First, we observed that UCHL1 knockdown in C2C12 myoblasts resulted in increased …

A New Model For Polar Growth In Mycobacteria: The Role Of Wag31 And Mmpl3 In Cell Wall Synthesis, Neda Habibi Arejan

Biology Dissertations - Archive

The disease Tuberculosis (TB) is caused by the pathogen Mycobacterium tuberculosis and was the cause of over one million deaths worldwide in 2023 (World Health Organization, 2023). TB treatment is difficult due to antibiotic tolerance and emerging resistance in Mtb strains. Mycobacterial cells have different regulatory mechanisms that allow them to adjust to myriad environmental stressors: these responses often lead to antibiotic tolerance. Therefore, studying responses to stress will lead to insights about antibiotic tolerance and treatment failure. Here, we specifically study two essential mycobacterial proteins, Wag31 and MmpL3, involved in cell wall metabolism. We show that Wag31 has distinct …