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Full-Text Articles in Molecular Biology

Targeting Pten For Therapy In Cancer And Ptenopathies, Emily Palumbo Jul 2019

Targeting Pten For Therapy In Cancer And Ptenopathies, Emily Palumbo

Graduate Theses and Dissertations

PTEN, a dual protein and lipid phosphatase, regulates a myriad of cellular functions including PI3K pathway signaling, cell migration, proliferation, invasion and apoptosis. PTEN mutations often lead to multiple malignancies, including prostate, breast, endometrial, skin and brain cancers, associated with hyperactive PI3K signaling. PTEN mutations have also been associated with a variety of other diseases, classified as PTEN Hamartoma Tumor Syndromes (PHTS). In addition, compromised function or reduced expression of PTEN due to non-genomic mechanisms are associated with many types of hyperproliferative diseases, such as restenosis and neoplastic diseases, including melanoma, lung, breast, prostate and colon cancers. Although PI3K pathway ...


Functional Characterization Of The Ovarian Tumor Domain Deubiquitinating Enzyme 6b, Jasmin M. D'Andrea Jun 2019

Functional Characterization Of The Ovarian Tumor Domain Deubiquitinating Enzyme 6b, Jasmin M. D'Andrea

Graduate Theses and Dissertations

The posttranslational modification ubiquitination is major regulatory mechanism used throughout cell signaling pathways such as cell cycle regulation and the DNA damage response. As such, the E3 ligases and their deubiquitinating enzyme counterparts, which conjugate and deconjugate ubiquitin to and from protein substrates respectively, must be tightly regulated to prevent aberrant cellular behaviors that could lead to diseases such as cancer.

Of the five families of deubiquitinating enzymes, the Ovarian Tumor Domain (OTU) family is fairly unique and under-studied; many of its family members hold a linkage specificity to certain ubiquitin chains and a number of them have been implicated ...


Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri Apr 2019

Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri

Graduate Theses and Dissertations

Genomic instability is a hallmark of disorders in which DNA replication and repair genes are dysfunctional. The tumor suppressor RECQ helicase gene BLM encodes the 3’-5’ DNA Bloom syndrome helicase BLM, which plays important roles during DNA replication, recombination and repair to maintain genome stability. Mutations within BLM cause Bloom syndrome, an autosomal recessive disorder characterized by growth defects, immunodeficiency, >10-fold higher sister chromatid exchange compared to normal cells, and an increased predisposition to a wide range of cancers from an early age. Single nucleotide polymorphisms or SNPs in BLM have been reported to be associated with susceptibility to ...


Conserved Glycine Residues Control Transient Helicity And Disorder In The Cold Regulated Protein, Cor15a, Oluwakemi Sowemimo Mar 2019

Conserved Glycine Residues Control Transient Helicity And Disorder In The Cold Regulated Protein, Cor15a, Oluwakemi Sowemimo

Graduate Theses and Dissertations

COR15A is a cold regulated disordered protein from Arabidopsis thaliana that contributes to freezing tolerance in plants by protecting membranes. It belongs to the (LEA) Late Embryogenesis Abundant group of proteins that accumulate during the later stage of seed development and are expressed in various parts of the plant. During freezing-induced cellular dehydration, COR15A transitions from a disordered structure to a mostly α-helical structure that binds and stabilizes chloroplast membranes when cells dehydrate due to freezing. We hypothesize that increasing the transient α-helicity of COR15A under normal conditions will increase its ability to bind and protect chloroplast membranes when cells ...


Biochemical And Proteomic Approaches To Determine The Impact Level Of Each Step Of The Supply Chain On Tomato Fruit Quality, Robert T. Madden Mar 2019

Biochemical And Proteomic Approaches To Determine The Impact Level Of Each Step Of The Supply Chain On Tomato Fruit Quality, Robert T. Madden

Graduate Theses and Dissertations

Fresh fruits and vegetables (FFVs) are the most frequently wasted foods because of their perishability and handling requirements. However, there is a lack of information on how much each step of the supply chain impacts FFVs quality, particularly on tomatoes, and what measures need to be taken for an immediate and effective impact on waste reduction. There is also no information on how the supply chain affects the proteome of the tomato and what proteins are differentially regulated by the most impactful steps of the supply chain. The objectives of the work presented on this thesis were to evaluate the ...


Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone Mar 2019

Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone

Graduate Theses and Dissertations

This dissertation covers a variety of the genetic and molecular abnormalities of lung adenocarcinoma with an emphasis on STK11 loss and its implications on immunotherapy response. Given that lung cancer is the leading cancer killer, novel therapies are in great demand. In particular, immunotherapy has shown some of the most promise in the last decade but remains limited due to nearly 80% of patients not significantly responding. This dissertation aims to molecularly characterize lung adenocarcinoma while attempting to explain the reason why patients with STK11 loss do not respond to immunotherapy.

In the first chapter we discuss the relationship between ...


Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher Jan 2019

Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher

Graduate Theses and Dissertations

Swine with severe combined immunodeficiency (SCID) are an emerging large animal model for biomedical research. There have been several SCID pig models described since our first discovery of naturally occurring SCID with mutations in Artemis (DCLRE1C) in 2012. SCID animals are particularly useful in biomedical research due to their lack of T, B, and sometimes NK cells. Absence of the adaptive immune system allows for human cell and tissue xenotransplantation into these SCID animals. The works described within this thesis are categorized under four main goals: (1) further characterization of the immune system of Art-/- SCID pigs, (2) development of ...


Ectopic Expression Of The Arabidopsis Homomeric Acetyl-Coa Carboxylase, Troy Matthew Bunch Jan 2019

Ectopic Expression Of The Arabidopsis Homomeric Acetyl-Coa Carboxylase, Troy Matthew Bunch

Graduate Theses and Dissertations

A number of economic and environmental imperatives have spurred an increased demand for biologically sourced, chemically reduced forms of carbon. Fatty acids, and closely related derivatives, represent an abundant form of such biological carbon. The biosynthesis of these molecules requires acetyl-CoA as a primer substrate, and malonyl-CoA as the extender substrate. Malonyl-CoA is generated by the carboxylation of acetyl-CoA, a reaction catalyzed by acetyl-CoA carboxylase (ACCase), which is thought to be an important determinant of the rate limiting reaction of fatty acid biosynthesis. In Arabidopsis, as in most dicotyledonous plants, two distinct isozymes catalyze this reaction, a cytosolic homomeric form ...