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Articles 1 - 7 of 7
Full-Text Articles in Medicine and Health Sciences
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Arts & Sciences Electronic Theses and Dissertations
Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …
A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey
A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey
Arts & Sciences Electronic Theses and Dissertations
Molluscum contagiosum virus (MCV) is a common human-specific poxvirus with a proclivity for
infecting children and the immune-compromised. A characteristic MCV infection is restricted to
the epidermal layers of the skin and can persist for weeks to years in an otherwise healthy
individual. The high clinical burden of MCV is at odds with our limited knowledge regarding how
it successfully evades the human immune response, which is in part due to the lack of an animal
model or cell line to propagate the virus. Through this dissertation, we have uncovered and
characterized a novel mechanism by which MC80, a protein …
Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal
Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal
Arts & Sciences Electronic Theses and Dissertations
The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …
A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey
A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey
Arts & Sciences Electronic Theses and Dissertations
The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …
Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar
Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar
Arts & Sciences Electronic Theses and Dissertations
Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …
Discovering Rare Hematopoietic Clones Harboring Leukemia-Associated Mutations Using Error-Corrected Sequencing, Andrew Lee Young
Discovering Rare Hematopoietic Clones Harboring Leukemia-Associated Mutations Using Error-Corrected Sequencing, Andrew Lee Young
Arts & Sciences Electronic Theses and Dissertations
Cancer is a heterogeneous group of diseases that currently takes over half a million lives per year in the United States alone. Our understanding of cancer has improved dramatically over the last forty years, beginning with the discovery that cancer is a disease of the genome. Currently, the set of somatic mutations found in malignancy are largely known. The specific somatic mutations driving an individual’s disease can be readily assessed at clinical presentation. Additionally, the functional consequences for many of these mutations are known as well as their role in tumorigenesis. Despite this understanding, a cure for cancer remains elusive. …
Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry
Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry
Arts & Sciences Electronic Theses and Dissertations
Various thymic APC subsets have been invoked in deletional tolerance and Treg cell induction, but previous studies either assessed total T cell numbers or used TCR transgenic lines, obscuring roles that individual thymic APC subsets might serve for particular antigen-specific T cell populations. Utilizing T cell receptor sequencing, we found that medullary thymic epithelial cells (mTECs) and bone marrow-derived (BM) APCs delete or select unique conventional and Treg cell TCR repertoires, demonstrating distinct roles for these APCs. We show that BM APCs and mTECs each contribute to Aire-dependent T cell tolerance development, albeit through either cooperative or autologous antigen presentation …