Medical Molecular Biology Commons^™

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Investigations In The Cellular And Molecular Biology Of Human Airway Mucociliary Tissue, Vincent Manna

Graduate School of Biomedical Sciences Theses and Dissertations

Our laboratory has integrated the use of a human-derived, in vitro model of airway mucociliary tissue. We isolate human nasal epithelial cells (HNECs) from the nasal mucociliary tissue of donors with a small brush and expand the airway progenitor cells in culture. The HNECs are then seeded onto semi-permeable transwell inserts. The inserts are in contact with the media in the lower chamber but don’t contain media in the upper chamber therefore the cells are exposed to the air while drawing nutrients from the media below, this is called the Air-Liquid Interface (ALI). HNECs cultured at the ALI initiate a …

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …

Lipocalin-2 Ameliorates The Signs And Outcomes Of Diabetes Mellitus In An Animal Model, Saeeda Mohammed Al Jaberi

Theses

Lipocalin-2 (LCN2) is a new adipocytokine consisting of 198 amino acids. It is also referred to as neutrophil gelatinase-associated lipocalin, siderocalin, uterocalin, α1-microglobulin related protein, or 24p3. LCN2 belongs to a large group of transport proteins that are capable of carrying small and lipid-soluble molecules in blood circulation. It has two membrane receptors, megalin/glycoprotein GP330, which binds human LCN2 and SLC22A17 or 24p3R, which forms complexes with mouse Lcn2 protein. LCN2 is encoded by a gene located at chromosome locus 9q34.11. LCN2 was initially isolated from neutrophil granules released at the site of infection and inflammation in humans and from …

Replication Protein A (Rpa) Targeting Of Uracil Dna Glycosylase (Ung2), Derek Chen, Brian P Weiser

Rowan-Virtua Research Day

Replication Protein A (RPA) is a single stranded DNA binding protein which stabilizes ssDNA for replication and repair. One function of RPA is to bind the DNA repair enzyme uracil DNA glycosylase (UNG2) and direct its activity towards ssDNA dsDNA junctions.

UNG2 removes uracil bases from DNA which can appear through dUMP misincorporation or through cytosine deamination. If uracil is present instead of a cytosine, then the original GC pair becomes a GU pair. The uracil will then base pair to adenine in the replicated daughter strand. This results in a GC → AT mutation that could contribute to cancer …

Substrate-Dependent Modulation Of Sirt2 By A Fluorescent Probe, 1-Aminoanthracene, David Bi, Prashit Parikh, Jie Yang, Brian P Weiser

Rowan-Virtua Research Day

Sirtuin isoform 2 (SIRT2) is an enzyme that catalyzes the removal of acyl groups from lysine residues. SIRT2’s catalytic domain has a hydrophobic tunnel where its substrate acyl groups bind. Here, we report that the fluorescent probe 1-aminoanthracene (AMA) binds within SIRT2’s hydrophobic tunnel in a substrate-dependent manner. AMA’s interaction with SIRT2 was characterized by its enhanced fluorescence upon protein binding (>10-fold). AMA interacted weakly with SIRT2 alone in solution (Kd = 37 μM). However, when SIRT2 was equilibrated with a decanoylated peptide substrate, AMA’s affinity for SIRT2 was enhanced ∼10-fold (Kd = 4μM). The peptide’s decanoyl chain and …

Cyclin C Determines Cell Fate In Response To Oxidative Stress And Proteasome Inhibition, David C. Stieg

Graduate School of Biomedical Sciences Theses and Dissertations

In response to various sources of cellular stress, the coordination of intracellular events is necessary to elicit the appropriate molecular response. In particular, the reprogramming of gene expression by stress-specific transcription factors drives the activation of signaling pathways, triggering either cell survival or regulated cell death pathways. The Cdk8 kinase module (CKM) is a highly conserved transcriptional regulatory complex with a role in this decision. The CKM is composed of Cdk8, its activating partner cyclin C, and two scaffold proteins, Med12 and Med13. The CKM is a detachable subunit of the Mediator complex, which interacts with RNA polymerase II to …

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Publications

Biological Sciences; Physiology; Molecular Biology; Cell Biology

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …