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Translational Medical Research Commons™
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Articles 1 - 6 of 6
Full-Text Articles in Translational Medical Research
Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw
Dissertations & Theses (Open Access)
Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …
Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson
Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson
Dissertations, Theses, and Capstone Projects
A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …
Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino
Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino
MSU Graduate Theses
Recent insights into the pathological role of Nucleotide P2Y2 receptor suggest P2Y2R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y2R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y2R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y2 in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …
Parp1-Targeted Radiotherapies, Stephen Jannetti
Parp1-Targeted Radiotherapies, Stephen Jannetti
Dissertations, Theses, and Capstone Projects
Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …
Transcriptomics Of Learning, Pablo Iturralde
Transcriptomics Of Learning, Pablo Iturralde
Theses
Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …
Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer
Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer
University Scholar Projects
Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …