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Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations and Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Ut Gsbs News, Fall/Winter 2015, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

Efficacy Of Oral Anticoagulation In Stroke Prevention Among Sinus-Rhythm Patients Who Lack Left Atrial Mechanical Contraction After Cryoablation, José Martínez-Comendador, Javier Gualis, José Miguel Marcos-Vidal, Jonnatan Buber, Carlos Esteban Martín, Jesús Gomez-Plana, Miguel Angel Rodríguez, Ignacio Iglesias-Garriz, David Alonso, Carlos Soria, Eva Higuera Miguélez, Mario Castaño

The Texas Heart Institute Journal

The customary recommendation is that oral anticoagulation be withdrawn a few months after cryoablation for atrial fibrillation, independently of left atrial mechanical contraction in patients in sinus rhythm. Recently, a 5-fold increase in stroke has been described in sinus-rhythm patients who lack atrial mechanical contraction. One aim of this study was to evaluate the efficacy of oral anticoagulation in preventing postoperative stroke in such patients.

This prospective study divided 154 sinus-rhythm patients into 2 groups, depending on the presence (108 patients) or absence (46 patients) of left atrial mechanical contraction at 6 months after surgery, and monitored them annually for …

Underserved Adoptive Families: Disparities In Postadoption Access To Information, Resources, And Services, Robin M. Hartinger-Saunders Ph.D., Alex R. Trouteaud Ph.D.

Journal of Family Strengths

Parents who adopt children from the U.S. foster care system typically do so with assurances from the state that postadoption services will be accessible by the family, if needed, after the adoption is finalized. From the state’s perspective, the foremost purpose of these services is to ensure that the family remains intact, thereby avoiding adoption dissolution—a traumatic and costly outcome whereby the child is returned to state custody. This study looks specifically at underserved adoptive families—those who report needing specific services after adoption finalization, yet who are then unable to access these needed services through the state because of various …

Persistence, Motivation, And Resilience: Older Youth Aging Out Of Foster Care Attending Historically Black Colleges And Universities (Hbcus), Belinda Davis Smith Ph.D., Lcsw, Dana Burdnell Wilson Msw, Ph.D., Lcsw, Tiffany Y. Lane Ph.D., Msw, Sonja V. Harry Ph.D., Msw, Isiah Marshall Jr., Ph.D., Msw

Journal of Family Strengths

Persistence, Motivation and Resilience: Older Youth Aging Out of Foster Care

Attending Historically Black Colleges and Universities

ABSTRACT

Many young adults involved with the child welfare system have a unique set of circumstances and needs. As they come of age, separated from their families of origin, additional services and supports are warranted to achieve their goals in life. This qualitative study explores the experiences of youth who have been impacted by the foster care system and are enrolled at a Historically Black College and University (HBCU) in the Mid-Atlantic region. Using a phenomenological approach, participants were interviewed regarding their motivation …

"Then You Fall Off": Youth Experiences And Responses To Transitioning To Homelessness, Diane M. Santa Maria, Sarah C. Narendorf, Noel Bezette-Flores, Yoonsook Ha

Journal of Family Strengths

Introduction: This study aims to broaden our understanding of the experience of homelessness and unstable housing in youth. While quantitative research highlights risk factors associated with experiencing homelessness as a youth, little qualitative research has been conducted to explore the lived experience of this transition to homelessness or unstable housing and how youth respond to becoming homeless. This study utilizes data from youth descriptions of their experiences to understand the context of the transition to homelessness and how youth manage this transition.

Methods: A qualitative study with a quantitative component was conducted with a nonprobability sample of homeless youth aged …

Underserved Populations In The United States: Research, Response And Resilience, Robert Sanborn, Angelo P. Giardino, William V. Flores, E. Christopher Lloyd

Journal of Family Strengths

Angelo P. Giardino, Robert Sanborn, William V. Flores and E. Christopher Lloyd discuss the latest issue of the Journal of Family Strengths.

Stem Cell Banking: An Update On Current Scenario, Harshal Deshpande, Sreelatha Akkala, Suman Rasquinha, Smita Karpate

Faculty, Staff and Student Publications

The emerging medical science coupled with biotechnological innovations is paving way for an exciting science - stem cell research. The researchers in the area of stem cell banking are exploiting the factual impending market worldwide. The possible clinical application of stem cells has generated great curiosity amongst medical professionals and general public. No only this, but stem cell research can be used for the treatment of widespread diseases like diabetes, Parkinson's disease, severe aplastic anemia, leukeamias, etc. The present article highlights the historical perspective about the stem cell banking along with an overview of global scenario of stem cell banking …

Improving Attenuation Correction In Hybrid Positron Emission To Mography, Hua Asher Ai

Dissertations and Theses (Open Access)

Hybrid positron emission tomography imaging techniques such as PET/CT and PET/MR have undergone significant developments over the last two decades and have played increasingly more important roles both in research and in the clinic. A unique advantage PET has over other clinical imaging modalities is its capability of accurate quantification. However, as the most critical component of PET quantification, attenuation correction in hybrid PET systems is challenged in several different aspects, including the spatial- temporal mismatch between the PET emission images and the associated attenuation images provided by the complementary modality, and the difficulty in bone identification in the MR-based …

Gating Mechanisms Of The Canonical Trp Channel Isoform Trpc4, Dhananjay P. Thakur

Dissertations and Theses (Open Access)

Non-selective cation channels formed by Transient Receptor Potential Canonical (TRPC) proteins play important roles in regulatory and pathophysiological processes. These channels are known to be activated downstream from phospholipase C (PLC) signaling. However, the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. Uniquely, TRPC4 is maximally activated only when two separate G protein pathways, G_q/11 and G_i/o, are co-stimulated, making it a coincidence detector of G_q/11- and G_i/o -coupled receptor activation. Using HEK293 cells co-expressing mouse TRPC4β and selected G protein-coupled receptors, I observed that coincident stimulation of G_i/o proteins and …

Investigating The Role Of Cholesterol Metabolism And Synthesis In Metastasis And Radiation Response In Aggressive Subtypes Of Breast Cancer, Adam Wolfe

Dissertations and Theses (Open Access)

Aggressive breast cancers, triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC), metastasize at a high rate and are notoriously resistant to standard treatments. Research has shown diets high in cholesterol increase the incidence of aggressive breast cancers and pre-clinical research has shown cholesterol can fuel the growth of breast cancer in vivo. Studies at MD Anderson have shown that IBC patients taking cholesterol lowering drugs, statins, have improved survival outcomes, and also statins can improve the response to radiation in vitro. Furthermore, statins have been shown to target the cells with stem like-properties called cancer stem cells (CSCs) which …

New Insights On The Role Of Jmjd2a In Cancer Progression, Yuan Gao

Dissertations and Theses (Open Access)

Changes in chromatin architecture are known to be one of the underlying causes of cancer because of its ability to alter gene transcription. Histone methylation is one of the most intricate epigenetic marks because it adds multiple layers of modification on the targeted sites. Therefore, many studies have brought histone methylases and demethylases into focus, hoping to decipher their roles in cancer progression. Among these enzymes, JMJD2A is the first to shown to have demethylation activity against trimethylation, and to regulate gene expression, development, and cancer progression. While many studies have mainly focused on its role in transcriptional regulation, only …

Identification Of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing, Timothy B. Palculict

Dissertations and Theses (Open Access)

Wilms tumor, a childhood tumor arising from undifferentiated renal mesenchyme, is diagnosed in North America at a frequency of 1 in 10,000 live births and accounts for 5% of all pediatric cancers. The etiology of Wilms tumor is heterogeneous with multiple genes known to have an effect on Wilms tumor development; however, these genes are rarely associated with familial Wilms tumor. Gene mutations in WT1, WTX, CTNNB1 and TP53 are observed in a third of sporadic tumors, while the causative gene(s) responsible for familial Wilms tumor are largely unknown. Approximately 2% of Wilms tumor patients have a family …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations and Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Merlin Mediated Regulation Of Hair Follicle Morphogenesis, Megan K. Fentress

Dissertations and Theses (Open Access)

Epidermal homeostasis is paramount for the ongoing function of the skin as the primary barrier between a mammalian organism and the external environment. Homeostasis is achieved through a complex and delicate balance of cell death, cell proliferation and cell differentiation. Critical for regeneration and maintenance of the skin are epidermal stem cells. Within the epidermis two distinct stem cell compartments exist, the bulge and interfollicular/basal stem cell niches, which play a central role in the regeneration of the epidermis through self-renewal and contribution to the differentiated cells of the epidermis. The bulge stem cell niche is established early in epidermal …

Ex Vivo Expanded Cord Blood Natural Killer Cells As A Novel Therapeutic For Multiple Myeloma, Nina Shah

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is the second most common hematologic malignancy in adults and, to date, is incurable. Allogeneic natural killer (NK) cells are active in various hematologic malignancies and may have a role against MM. Umbilical cord blood is a potential source for allogeneic NK cells and ex vivo expanded umbilical cord blood-derived NK (CB-NK) cells demonstrate activity comparable to that of peripheral blood-derived NK cells. However, large-scale expansion of these cells is required for clinical translation. Here we studied a potential method for ex vivo expansion of NK cells from fresh and cryopreserved CB. Using artificial antigen presenting cells …

In Vivo Significance Of The Mdm4 And P73 Interaction During Development And Tumorigenesis, Mehrnoosh Tashakori

Dissertations and Theses (Open Access)

The tumor suppressor protein p53 is negatively regulated by Mdm4 protein. The significance of such regulation was determined from mouse models. Mdm4-deficient mice are embryonic lethal at E7.5 in a p53-dependent manner. p73, a member of the p53-family, is a transcription factor with tumor suppressor activity. In vitro studies show that Mdm4 binds to p73 and, further, comprehensive biochemical studies revealed that Mdm4 has higher affinity for p73 than p53. However, little is known about the significance of the Mdm4 and p73 interaction in vivo. This study aimed to elucidate the biological consequences of this interaction during embryogenesis …

Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao

Dissertations and Theses (Open Access)

Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment …

Investigating The Interaction Of Aurka And Ube2c In Colorectal Cancer Cells, Apurva M. Hegde

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Among the many genomic aberrations previously implicated in colorectal cancer, recurrent amplification of chromosome 20q is frequently associated with liver metastasis. Previous research in our lab identified a gene signature on chromosome 20q associated with colorectal cancer progression. In this study, one of the genes in the signature, the ubiquitin conjugating enzyme UBE2C, was identified through preliminary bioinformatics analysis as a candidate for further examination of its role in CRC progression. Co-expression analysis of UBE2C in tumor-normal datasets from the public database Oncomine revealed all the …

Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith

Dissertations and Theses (Open Access)

Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations and Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li

Dissertations and Theses (Open Access)

A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.

Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …

Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases, Donghyun Joo

Dissertations and Theses (Open Access)

Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a role in various cellular processes such as proliferation, differentiation (mainly through NF-κB signaling) and death (via apoptosis signaling). Recently, linear ubiquitination by LUBAC (linear ubiquitin chain assembly complex) was reported to have a regulatory function in TNF-α mediated NF-κB activation. Although LUBAC is suggested to control not only NF-kB signaling but also the apoptosis pathway, the precise mechanism of apoptosis regulation remains unknown. Moreover, NF-κB and apoptosis pathways have opposed but fundamental functions for various cellular processes. Although these two pathways actively interplay to balance the death and survival, the …

Histone H3 K4 Methylation Regulates The Spindle Assembly Checkpoint Through Direct Binding Of Multiple Checkpoint Components And Cdc20, Andria C. Schibler

Dissertations and Theses (Open Access)

Histone H3K4 methylation is conserved across species and is associated with active transcription. By using Saccharomyces cerevisiae, we found histone H3K4 methylation has a previously unknown role in regulating mitosis through the Spindle Assembly Checkpoint. The Spindle Assembly Checkpoint ensures duplicated chromosomes are segregated correctly and each daughter cell receives one full copy of the genome. Our data show SET1 mutants and histone H3K4 mutants display a resistance to the mitotic poison, benomyl. Moreover methylated histone H3 directly binds to Spindle Assembly Checkpoint proteins Bub3 and Mad2 as well as the activator of the Anaphase Promoting Complex (APC) protein …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

Regulation Of Autoimmune Germinal Center Reaction By Tfh Cells And Application Of Tfr-Like Cells For The Treatment Of Autoimmune B Cell Responses, Young Uk Kim

Dissertations and Theses (Open Access)

Excessive follicular helper T (Tfh) cell responses to self-antigens are associated with antibody-mediated autoimmune diseases in humans including systemic lupus erythematosus (SLE). Numeral and functional aberrations of T regulatory T (Treg) cells are common in patients with autoimmune diseases. Although different types of immunosuppressive agents have been used clinically to treat antibody-mediated autoimmune diseases, they generally have side effects due to the lack of target-specificity. To minimalize the adverse effects, there is a need to develop target-specific therapeutics which specifically control auto-reactive B cell responses and auto-reactive Tfh cell responses. Recent studies unveiled that Foxp3⁺ Treg cells expressing CXCR5 …

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

Dissertations and 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 …

Yap1 Expression Predicts Sensitivity To Dual Akt/P70s6k Inhibition In Ovarian And Uterine Malignancies, Rebecca A. Previs

Dissertations and Theses (Open Access)

Purpose: The PI3K/AKT/P70S6K pathway is an attractive therapeutic target in ovarian and uterine malignancies due to its high rate of dysregulation and key roles in tumor growth. Here, we examined the biological effects of MSC2363318A, which is a novel inhibitor of AKT1, AKT3, and P70S6K.

Experimental Design: Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. Moreover, in vitro experiments (MTT, Western blot analysis, plasmid transfection, and reverse phase protein array [RPPA]) were carried out to characterize underlying mechanisms and potential biomarkers of response.

Results: MSC2363318A decreased tumor growth …

Assessment Of Uncertainty In Planning And Dose Delivery Of Proton Therapy In An Iroc- Houston Qa Phantom Due To Variable Ct Technique And Proton Energy, Mattie M. Mcinnis

Dissertations and Theses (Open Access)

As proton therapy increases in popularity, so does the need for effective quality assurance. Proton therapy institutions participating in NCI funded clinical trials rely heavily on the credentialing and auditing services of IROC-H and therefore the process must be well understood. The purpose of this project is to understand the uncertainties in proton therapy treatment planning for the IROC-H proton phantom QA program due to variations in CT technique and proton energy. It was hypothesized that variations in CT technique and proton energy will alter the delivered dose distributions of typical proton treatments by reducing the percent of passing pixels …