Cell and Developmental Biology Commons^™

Hematologic Manifestations Of Parvovirus B 19 Infection, Ghada Algwaiz, Abrar Alharbi, Khuloud Alsehaim, Ali Alahmari, Riad El Fakih, Mahmoud Aljurf

Hematology/Oncology and Stem Cell Therapy

Parvovirus B19 virus infection is widespread among humans because of its highly infectious and obstinate nature, with up to 80% of the population testing positive for IgG antibodies against the virus. Pronormoblasts observed in biopsy are the hallmarks of PVB19 infection. In addition, PVB19 affects the skin, heart, brain, joints, and liver and can be diagnosed through antibody detection or DNA detection via PCR. Due to its capsid proteins’ high affinity for bone marrow receptors, its main presentation is the suppression of bone marrow functions. It has been shown to affect patients with hemolytic anemia and patients with hematological malignancies, …

Modulation Of Polyamines To Elucidate Function Within Osteogenesis Of Mesenchymal Stromal Cells, Amin S. Cressman

Cal Poly Humboldt theses and projects

Snyder-Robinson Syndrome (SRS), an X-linked intellectual disability that arises in children, exhibits debilitating phenotypes like severe osteoporosis. These patients demonstrate an inability to produce mineralized new bone in comparison to the rate at which bone is resorbed, thus leading to weaker skeletal structure and atraumatic fractures. The known cause of SRS is due to loss-of-function mutations within the gene that encodes Spermine Synthase (SMS). Loss of SMS enzymatic activity, which catalyzes the conversion of polyamines spermidine into spermine, demonstrates an increase in the spermidine/spermine ratio in all documented cases of this disorder. The involvement of polyamines in osteogenesis is still …

Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie

Cal Poly Humboldt theses and projects

Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …

Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina

Electronic Theses and Dissertations, 2020-

Pancreatic cancer overall has a poor five-year survival rate of less than 8%. Well-tolerated regimens and immune cell infiltration to promote anti-cancer treatments are major challenges. Studies described herein leveraged testing different combinations/doses of polyamine targeting inhibitors to further understand the impact of targeting key polyamine pathway mediators in pancreatic ductal adenocarcinoma (PDAC). Placebo controls were compared to groups treated with difluoromethylornithine (DFMO, a polyamine biosynthesis inhibitor of ornithine decarboxylase), different polyamine transport inhibitors, and compound combinations in strategies for polyamine blockage therapy (PBT). Informatic analyses showed that the dysregulation of key polyamine pathway mediators are associated with poor patient …

Targeting The Bcl6 Transcription Factor In Ovarian Cancer, Harrison H. Parent

Honors Theses and Capstones

Ovarian cancer is one of the most common reproductive malignancies for women in the United States, as well as one of the deadliest. Many deaths attributed to ovarian cancer, as well as cancer generally, are due to metastasis of the original tumor to different tissues throughout the body. The BCL6 transcription factor has been identified to play a key role in the metastasis of these tumors, as well as the invasion of these cancer cells through mesothelial cell layers, which contributes to ovarian cancer’s unique metastatic behavior. In an attempt to target these metastases and prevent mesothelial penetration, drugs were …

Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma

Dissertations

Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …

Genetic Underpinnings Of Novel Trait Development In A Euwallacea-Fusarium Mutualism, Elaina J. Spahr

Graduate Theses, Dissertations, and Problem Reports

Evolutionary Developmental Biology seeks to answer fundamental questions about the mechanisms underlying the evolution and innovation towards increasing structural complexity within the body plan. The ambrosia symbiosis, a polyphyletic group of xylem-feeding beetles, provides a wealth of diversity in novel pouch-like structures called mycangia. This diversity could serve as a rich model for understanding how mutualisms may prompt structural innovation and diversification in a host organism. The ambrosia symbiosis has become a fast-growing research subject in entomology and forest pathology but has yet to experience the same attention under the lens of evolutionary developmental genetics.

Development of mycangia was examined …

Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, Mingxiang Zhang

Graduate Theses, Dissertations, and Problem Reports

Oocyte developmental competence or oocyte intrinsic quality describes the capability of oocytes to resume meiosis, cleave and develop to blastocyst stage after fertilization, implant and develop to term in a good health. A growing number of evidences indicate that the majority of embryonic mortality occurs during early embryonic development in different species, including human, horse and cattle primarily due to poor oocyte quality. Maternal effect genes are key aspects of oocyte quality, which are transcribed during the process of oogenesis and folliculogenesis. The maternal factors are accumulated in oocytes, orchestrating various early developmental events including fertilization, epigenetic reprogramming and zygotic …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Identifying Adp-Ribosylation As The Biochemical Signal That Marks Dna-Protein Crosslinks For Sprtn-Dependent Proteolysis, Katelyn Hurley

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) form when proteins covalently attach to DNA. It is estimated that hundreds of DPCs form in our cells each day. Because these lesions are cytotoxic, mammalian cells have evolved multiple intricate repair systems to remove DPCs and restore genome integrity. One mechanism mammalian cells rely on for DPC repair is direct proteolysis by the metalloprotease, SPRTN. While it is known that SPRTN degrades a heterogenous array of DPCs, including both naturally occurring and chemically induced, how SPRTN selects DPCs amongst chromatin-associated proteins remains unknown. Our main objective is to determine how DPC repair is regulated. In Chapter …

Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, Andrew Rhiner

Electronic Theses and Dissertations

A20 Inhibitor of NF-κB (ABIN1/TNIP1) is a known regulator of TNFα signaling induced cell death and inflammation. The regulatory activity has been attributed to ABIN1’s recruitment of the ubiquitin editing enzyme TNF-α-induced protein 3 (TNFAIP3/A20) to Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The regulation of RIPK1 by ABIN1 and A20 relies on a third player, linear ubiquitin chain assembly complex (LUBAC), which is involved in the recruitment of ABIN1 to RIPK1. Loss of LUBAC or ABIN1 is embryonic lethal, but loss of A20 is not embryonic lethal. The embryonic lethality due to loss of ABIN1, paired with the lack of lethality …

Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, Neysha Tirado-Class, Caitlin Hathaway, Wendy K. Chung, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

Chung–Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in PHIP (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two PHIP missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin …

Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart

Legacy Theses & Dissertations (2009 - 2024)

Cellular stress is something that a cell deals with on a regular basis. Fortunately, there are several different mechanisms that are set in place in order to deal with them. Depending on the stress present in the cell there will be different stress response pathways that are activated in order to mitigate the stress or initiate cellular death mechanisms. Transcription factors (TFs) are key components within these pathways, and this will be the focus of this thesis. TFs within mammalian stress response pathways are tasked with the essential regulation of multiple genes within these pathways and are oftentimes linked with …

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …