Cell and Developmental Biology Commons^™

Characterizing The Combination Of Rpa Inhibitors With Parp Inhibitors In High-Grade Serous Ovarian Cancer, Yat Tang

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) is the most common and deadly gynecologic malignancy. HGSC patients with BRCA1/2 mutations have homologous recombination deficiency (HRD), requiring parallel pathways to maintain genome integrity (e.g., PARP1, PARP2). Approximately 50% of ovarian carcinomas are estimated to exhibit HRD. For the remaining 50% and the large percentage of HRD patients with acquired or innate resistance to single-agent PARP inhibitors, there is a need to develop alternative therapeutic strategies.

Replication Protein A (RPA) is a heterotrimeric protein crucial for genome maintenance. Phosphorylation of RPA in DNA damage response (DDR) is a negative regulator of DNA end resection. …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

A Transcriptomic Exploration Of Hawaiian Drosophilid Development And Evolution, Madeline M. Chenevert

LSU New Orleans Theses and Dissertations

One in four known species of fruit flies inhabit the Hawaiian Islands. From a small number of colonizing flies, a wide range of species evolved, some of which managed to reverse-colonize other continental environments. In order to explore the developmental pathways, which separate the Hawaiian Drosophila proper and the Scaptomyza group that contains reverse-colonized species, the transcriptomes of two better-known species in each group, Scaptomyza anomala and Drosophila grimshawi, were analyzed to find changes in gene expression between the two groups. This study describes a novel transcriptome for S. anomala studies as well as unusual changes in gene expression …

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

The Role Of E3 Ubiquitin Ligase Fbxo9 In Normal And Malignant Hematopoiesis, R. Willow Hynes-Smith

Theses & Dissertations

Hematopoiesis is a critical system that provides blood cells necessary for nutrient and oxygen transfer throughout an organism and for protection from harmful agents. It is maintained throughout life by the hematopoietic stem cells (HSCs) that reside within the bone marrow (BM) and are responsible for providing billions of new cells each day. HSCs maintain a careful balance between a quiescent state, that sustains the integrity of the stem cells, and a proliferative state, that provides new cells to replenish those that undergo apoptosis. Hematopoiesis is regulated by a variety of intrinsic pathways and extrinsic signals such as cytokine signaling, …

Hdac1 Is A Required Cofactor Of Cbfβ-Smmhc And A Therapeutic Target In Inversion 16 Acute Myeloid Leukemia, Lisa E. Richter

Theses & Dissertations

Acute myeloid leukemia (AML) is a neoplastic disease characterized by the uncontrolled proliferation and accumulation of immature myeloid cells. A common mutation in AML is the inversion of chromosome 16 [inv(16)], which generates a fusion between the genes for core binding factor beta (CBFB) and smooth muscle myosin heavy chain (MYH11), forming the oncogene CBFB-MYH11. The expressed protein, CBFβ-SMMHC, forms a heterodimer with the key hematopoietic transcription factor RUNX1. Although CBFβ-SMMHC was previously thought to dominantly repress RUNX1, recent work suggests that CBFβ-SMMHC functions together with RUNX1 to activate transcription of specific target genes.

Targeting the …

Ecdysoneless, A Novel Regulator Of Ca2+ Homeostasis And Metabolism, Aniruddha Sarkar

Theses & Dissertations

The hallmarks of cancer include sustained proliferation and survival in the face of cellular stresses imposed by the oncogenic drive, as well as metabolic rewiring for tumor growth under adverse nutritional conditions. Adaptive alterations in key biochemical networks that underlie metabolic rewiring represent potential opportunities to develop new therapeutic strategies against cancer.

My thesis focuses on mammalian Ecdysoneless (ECD), a conserved homolog of the fly Ecdysoneless gene product, which engages fundamental cell biological processes of ER stress, Ca²⁺ signaling and metabolism to help sustain the oncogenic drive in tumor cells. Recent studies from our laboratory provide a clear evidence …

Molecular Insights Into Major Peripheral T-Cell Lymphoma Entities With Advances In A Representative Model System, Tayla B. Heavican

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a group of complex clinicopathological entities associated with an aggressive clinical course. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the two most frequent categories accounting for more than 50% of PTCLs. Gene expression profiling (GEP) defined molecular signatures for AITL and delineated biological and prognostic subgroups within PTCL-NOS (PTCL-GATA3 and PTCL-TBX21). Genomic copy number analysis and targeted sequencing revealed unique genomic abnormalities and oncogenic pathways, indicating distinct oncogenic evolution. PTCL-GATA3 exhibited higher genomic complexity characterized by frequent loss or mutation of tumor suppressor genes targeting the CDKN2A/B-TP53 axis and PTEN-PI3K pathways. …

Mechanism Of Bax/Bak Activation In Apoptotic Signaling, Kai Huang

Theses & Dissertations

The Bcl-2 family proteins, including the anti-apoptotic members, pro-apoptotic effectors Bax/Bak, and the BH3-only proteins, are key components of the mitochondrial apoptotic pathway. The BH3-only protein Bid is critical for the mitochondrial pathway of apoptosis after TRAIL-induced death receptor activation. However, the mechanism of Bid activation during TRAIL-induced apoptosis is unclear. By putting back wild-type and mutants of Bid in Bid deficient (Bid KO) and Bid/Bax/Bak TKO colon cancer cells, we demonstrated that cleavage by caspase 8 and mitochondrial targeting are critical events for Bid activation. One of the biggest mysteries in apoptosis is how Bax/Bak was activated by BH3-only …

A "Choose-Your-Own" Classroom-Based Activity That Promotes Scientific Inquiry About Rna Interference, Jeremy L. Hsu

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

RNA interference (RNAi), the process that results in the degradation of a target gene’s mRNA, is a fundamental part of eukaryotic gene regulation and is also an important molecular technique that allows for experimental manipulation of gene expression without altering DNA sequences. Despite the importance of RNAi, there have been relatively few lecture-based activities designed to teach about the consequences of this process and counter common misconceptions. I present here an inquiry-based activity that is centered around a “choose your own experiment” design where students generate hypotheses and critically evaluate their ideas by choosing several simulated experiments. The activity presents …

‘Am I Turning Into A Man?’ Experiences Of Pakistani Women With Pcos, Rida E Zehra Zaidi

MSJ Capstone Projects

According to the National Institutes of Health, 20 – 25% of all regularly ovulating women have PCOS. This disorder has a range of visible symptoms including excessive weight gain, hirsutism, acne, and hair loss among others. These symptoms make it difficult for women with the syndrome to fit the femininity ideals of the society, as it demands female bodies to be slim, smart, hair less, and to have porcelain skin and regular menstrual cycles. Women with PCOS and other health problems in Pakistan spend all their lives fighting unnecessary battles. This struggle has severe impacts on their physical and mental …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

Investigating The Relationship Between Hormone Receptors Dax-1 And Estrogen Receptor Within Prostate Cancer Cell Lines, Meghana G. Vijayraghavan

Master's Theses

Prostate cancer (PCa) is estimated to be the second leading cause of cancer-related deaths among men in the United States in 2019. While most prostate tumors rely on androgens for growth signaling, there are subsets of tumors that become androgen-resistant, therefore resisting conventional androgen-depravation therapy. Consequently, research has focused on targeting different hormone receptors for novel therapeutics. One such receptor is Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1). DAX-1 is known to interact with other hormone receptors, such as androgen receptor (AR) and estrogen receptors (ERs) to suppress the proliferative effects …

Maternal Immunity: Preimplantation Preparation And Spatial Distribution Of Ccl19, Ashleigh Elbert

Electronic Theses & Dissertations

Maternal Immunity: Preimplantation preparation and the role of CCL19

An Abstract of the thesis by

Ashleigh R. Elbert

The maternal uterus in mammals undergoes extensive remodeling in preparation for implantation of the semi-allogenic embryo. Activation of the T cell homing receptor, CCR7, regulates multiple aspects of adaptive immunity. Genetic deletion of CCR7 reduces T regulatory (T Reg) cell migration into mouse uteri and decreases embryo implantation. CCL19 and CCL21 are the sole ligands for CCR7. It is hypothesized that CCL19 expression could attract T reg cells into the pre-implantation uterus and provide local immune suppression prior to implantation. Sprague Dawley …

Genetics With Nettie And Friends: An Exploration Of Genetics In Children's Literature, Erin Soule, Madeleine Gray Burland

Honors Projects

Genetics with Nettie and Friends is an exploration of chromosomal disorders and its place within children's literature. The book provides a comprehensive examination the genetic composition of Downs syndrome, Williams Syndrome, and Duchenne muscular dystrophy at a level to increase understanding in children. This paper provides an insight to the development and construction of the children's book that is available for purchase on Barnes and Noble as well as why representation of genetic disorders in children's literature is needed.

The Black Identity, Hair Product Use, And Breast Cancer Scale, Dede Teteh, Marissa Ericson, Sabine Monice, Lenna Dawkins-Moultin, Nasim Bahadorani, Phyllis Clark, Eudora Mitchell, Lindsey S. Treviño, Adana Llanos, Rick Kittles, Susanne Montgomery

Health Sciences and Kinesiology Faculty Articles

Introduction
Across the African Diaspora, hair is synonymous with identity. As such, Black women use a variety of hair products, which often contain more endocrine-disrupting chemicals than products used by women of other races. An emerging body of research is linking chemicals in hair products to breast cancer, but there is no validated instrument that measures constructs related to hair, identity, and breast health. The objective of this study was to develop and validate the Black Identity, Hair Product Use, and Breast Cancer Scale (BHBS) in a diverse sample of Black women to measure the social and cultural constructs associated …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Gmr36a08, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 49927

• ID - GMR36A08
• Location - 2R: 18120673, 18124576
• Base pairs - 3903

Gmr40e08, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 41238

• ID - GMR40E08
• Location - 2R: 18162090, 18165058
• Base pairs - 2968

Gmr36a10, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 49373

• ID - GMR36A10
• Location - 2R: 18116788, 18120701
• Base pairs - 3913