Medicine and Health Sciences Commons^™

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 …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Evaluating Insurance Approval Rates Of Exome Sequencing And Its Effect On Minority Patients' Access To Genetic Care, Katlyn Frane

Dissertations & Theses (Open Access)

Exome sequencing (ES) is often a standard step in the genetic testing process for patients with rare or complex disease. Despite clinical implementation of ES, insurance companies (payers) continue to deny this test. We investigated if the payer barrier is influenced by payer type, and if other demographic or clinical information correlated to ES approval and obtainment. To do this, a retrospective chart and clinical database review was completed on patients seen at a tertiary care center and community-based clinic. Patient demographics, clinical indications, and testing recommendations and outcomes were used to assess ES approval and obtainment. We found that …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

10th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The Annual Postdoctoral Science Symposium (APSS) was initiated on August 4, 2011, by the MD Anderson Postdoctoral Association to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience.

APSS is a scientific symposium organized by postdoctoral fellows from The University of Texas MD Anderson Cancer Center that welcomes submissions and presentations from postdoctoral fellows from all Texas Medical Center affiliated institutions and other Houston area institutions. The APSS provides a professional venue for postdoctoral scientists to develop, clarify and refine their research as result of formal reviews and critiques …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Identifying Pathogenic Variants In Hereditary Cancer Syndrome Genes Via Tumor Molecular Profiling, Carol Nowlen

Dissertations & Theses (Open Access)

Tumor molecular profiling is often performed in order to direct cancer treatment options. However, because many of the genes analyzed on tumor molecular profiling overlap with genes known to be associated in the germline with hereditary cancer predisposition syndromes, tumor molecular profiling can unknowingly uncover germline predisposition to cancer development. In this study, we determined the number of patients with pathogenic variants (PVs) identified in BRCA1 and BRCA2 (BRCA1/2) via tumor molecular profiling at The University of Texas MD Anderson Cancer Center, then performed a retrospective chart review to determine the proportion of such patients that received germline …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations & Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations & Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Attitudes Of Clinicians Towards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations & Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations & Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …

Functional Analysis Of Synthetic Gene Circuits Controlling A Protein Pump In Yeast, Junchen Diao

Dissertations & Theses (Open Access)

Synthetic biology aims to build biological devices to understand living systems and explore new applications. Synthetic gene circuits such as genetic switches, oscillators and logic gates are at the core of many synthetic biology applications. These gene circuits often include a sensor/regulator protein capable to detect small molecules and then transduce them into a regulatory signal to generate measurable output. Similar signal transduction networks are also abundant in nature. However, in many natural and engineered scenarios, the output also affects the regulator/sensor protein. How such interactions between the regulator/sensor and the output affect synthetic gene circuit function has not been …

Spiritual Exploration In The Prenatal Genetic Counseling Session, Katelynn G. Sagaser

Dissertations & Theses (Open Access)

Religion and spirituality are important components of many individuals’ lives, and spiritual needs may present among persons receiving medical care. Spirituality has been demonstrated to be significant in the coping of women experiencing pregnancy complications (Breen et al. 2006; Price et al. 2007). To characterize the manner in which prenatal genetic counselors might address spiritual issues with their patients, we surveyed 283 patients receiving prenatal genetic counseling using the Brief RCope and a series of questions that examined interest in spiritual exploration. Counselors were concurrently surveyed to identify the spiritual language used within the session and the counselor’s perceived importance …