Cell and Developmental Biology Commons^™

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria ...

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated ...

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at ...

Genetically Explicit Model May Explain Multigenerational Control Of Emergent Turing Patterns In Hybrid Mimulus, Emily Simmons

Biology and Medicine Through Mathematics Conference

No abstract provided.

Identifying A Novel Hsp40/J-Domain Protein Inhibitor That Depletes Mutant P53 To Inhibit Cancer Malignancy, Shigeto Nishikawa

Research Days

Background: Accumulation of oncogenic mutant p53 (mutp53) greatly contributes to cancer progression. DNAJA1, which is a member of heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), plays a crucial role in the stabilization of misfolded forms of mutp53. Knockdown of DNAJA1 results in proteasomal degradation of misfolded mutp53, leading to tumor suppression. Currently, no HSP40/JDPs inhibitors are available in clinics.

Objectives/Goal: The goal of this study is to identify and characterize potential anti-cancer compounds which can induce mutp53 degradation by inhibiting HSP40/JDPs.

Methods/Design: To identify compounds that potentially bind to DNAJA1, we performed ...

Targeting Stress Granule Inhibition As A Novel Vulnerability Of Mutant P53, Elizabeth Thoenen

Research Days

Background: Tumor suppressor p53 (p53) inhibits cancer progression by transactivating genes involved in cell cycle arrest and apoptosis. P53 is mutated in half of all human tumors, which is well correlated with poor patient outcomes. Most of p53 mutations are missense mutations. Missense mutant p53 protein (mutp53) not only loses wild-type p53 (wtp53) transcription factor activity, but also shows oncogenic gain of function that enhances metastasis and drug resistance through protein-protein interactions. However, the exact mechanism by which mutp53 induces drug resistance is poorly described. Moreover, strategies that directly target mutp53 have been challenging.

Objectives/Goal: Our goal is to ...

Mdm2 Enhances Taxane Sensitivity By Inducing Stmn1 Degradation, Hongyi Ren

Research Days

Background: MDM2, a major E3 ubiquitin ligase of p53, is overexpressed in ~30% of human cancers. Evidence showed that overexpressed MDM2 has p53-independent oncogenic functions and is correlated with poor prognosis. Given that MDM2 overexpression is cancer-specific, therapies targeting vulnerabilities imposed by MDM2 overexpression may cause cell death specifically in cancer cells with minimum side effects.

Objectives/Goal: Our goal is to identify drugs that specifically kill MDM2-overexpressing cancer cells in a p53- independent manner.

Methods/Design: We generated p53-knockout (p53KO) and p53/MDM2-double knockout (DKO) SJSA-1 osteosarcoma cells in which MDM2 gene is amplified by using the CRISPR-Cas9 system ...

Segmentation Of Dna Lesions In Irradiated Mouse Brain Sections, Nicholas Cirone

Honors Capstones

The impacts of microscopy image analysis have resulted in better visualization of foci (spots) in cell nuclei. However, manual analysis of microscopy images is challenging regarding subjectivity in structure counting and identification. Recent computer algorithms have enabled cellular analysis through automatic segmentation that uses computational edges in digital images. In this project, the automatic segmentation workflow in the Zeiss Zen Blue 3.3 software was adapted to more closely reflect visualized foci in a cell. The foci represent DNA double strand breaks. The Zeiss LSM 900 microscope was used to collect maximal intensity projection images of γH2AX foci and super-resolution ...

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We ...

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the ...

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure ...

Exploring The Effects Of Varied Land Use On Elemental Concentrations Within Streams, Logan Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

It is well documented that human activity influences the chemistry of surrounding waters. As such, it is possible that there is a link between land use within a watershed and the chemical composition of the stream. The objectives of this study are to determine if varied land use does affect the concentrations of macronutrients and trace elements present in the streams of Northwest Arkansas, and if so, to determine what extent urban and agricultural development are responsible for these changes. Water samples were collected across 19 streams in the Northwest Arkansas region between January and March of 2022. Water samples ...

Investigating The Potential Role For The Nervous System In Controlling Regeneration In Nematostella Vectensis, Kristen Malir

Biological Sciences Undergraduate Honors Theses

Nematostella vectensis is a marine sea animal that has become a model for developmental and evolutionary research. Included in the phylum Cnidaria, N. vectensis’ was chosen as the model for this research. Not only can this animal go through asexual and sexual reproduction, but it also has the ability to regenerate. Although much research has been put forth in an effort to understand regeneration better, much is still unknown. The underlying mechanisms of regeneration in Cnidaria are illusive; however, studies within vertebrates have shown the substantial role of the nervous system. The objective of this experiment is to test if ...

Utilizing Pharmacology To Target Transcription Factors Involved With Cancer Onset And Development, Tristan D. Sanders

Mountaineer Undergraduate Research Review

Transcription factors (TFs) are a vital part of every living organism on earth, as they allow for the correct genes to be expressed while much of the genome is never used. They can fall victim to mutations or manipulations that lead to the deregulation of many genes within a cell. If specific genes are over/under-expressed, a cell may become cancerous and begin replicating into a tumor. It has been demonstrated that common TFs associated with cancer can be targeted using small molecule drugs, and a popular target of these drugs is the DNA binding site on the TF along ...

The Central Dogma: Gene Expression, Ayisha Sookdeo

Open Educational Resources

In this lesson plan, students will learn the basic structure and function of DNA and RNA. They will also learn the process of gene expression. Finally, students will learn about the scientific contributor, Ernest Everest Just, and his contributions to the field of Biology.

Zntppea As A Potential Photosensitizer In Photodynamic Therapy, Marly Welborn, Joseph E. Bradshaw

Scholars Day Conference

Photodynamic therapy (PDT) is an emerging treatment that is used against certain types of cancer and other diseases. It functions using a photosensitizer in the presence of light that contributes to cell death in the desired tissues. This research centered on the development of a novel water-soluble porphyrin that could be utilized as a photosensitizer. Using ethanolamine the resulting compound, ZnTPP-EA, was created. Purification and characterization was carried out. The ZnTPP-EA was tested on the A549 lung cancer cell line using an MTT assay under light and dark conditions to assess the compound's effectiveness as a photosensitizer for PDT.

Jag1 Role In The Extravasation Of Metastasized Tnbc Tumor Cells, Bhavya Vegesna '23

Student Publications & Research

Breast cancer is the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) is an aggressive subclass defined by its lack of hormonal receptors and HER2 amplification. Although TNBC only accounts for 15% of all invasive breast cancers, there are limited therapeutic options for patients with TNBC. Although breast cancer patients have a favorable prognosis if their tumor is detected early, patients with TNBC are prone to earlier recurrence and local/distant metastasis. Consequently, patients with metastatic TNBC have <15% relative 5-year survival rate. The development of metastasis in TNBC is a complex and poorly understood process that includes multiple steps such as genetic and epigenetic alterations, angiogenesis, epithelial-to-mesenchymal transition (EMT), intravasation, and extravasation. Expression of JAGGED-1 (JAG1), a Notch ligand, correlates with metastatic status and poor survival in clinical data. However, the exact mechanism in which JAG1 increases metastasis is unknown. We hypothesize that JAG1 increases metastasis by interacting with endothelial cells. In order to test this idea, we generated JAG1-knockout cells using CRISPR/Cas9 technologies and then modeled the extravasation of these cells compared to JAG1-positive cells. Specifically, we interrogated lung capillary extravasation after intravenous injection of TNBC cells. The lung was chosen due to the propensity of TNBC cells to invade the lung. Preliminary data demonstrates that JAG1 presented in tumor cells acts as a signaler to permit and promote extravasation and metastasis of the cancer cells. For further studies, the long term effects of tumor derived JAG1 will be studied to understand the consequences of JAG1 mediated extravasation on metastatic burden and survival.

Aeromonas Phage Research And The Public Health Impact Of Antibiotics In Aquaculture Workers, Madelyn Merchant

Honors Projects

One of the most common fish diseases in aquaculture is Aeromonas infection. The most common way to treat this infection is through antibiotics. The bacteria in the fish can become antibiotic-resistant and perpetuate the disease. The diseases in fish create a huge financial loss and the industry loses $6 billion per year due to diseases in fish. An alternative to antibiotics is bacteriophage which causes less environmental degradation and is better for human gut flora. In aquaculture there have been examples of aquaculture workers becoming sick from the water in aquaculture ponds as well as from people eating the fish ...

Exchange Protein Directly Activated By Camp (Epac1) Protects Human Endothelial Cells From Tumor Necrosis Factor-⍺ (Tnf-⍺) Induced Cell Death, Anh Luu, Abigail Carpenter, Rosetta Tolley

ONU Student Research Colloquium

Millions of people are affected by diseases involving inflammatory states such as sepsis. Sepsis is associated with elevated tumor necrosis factor alpha (TNF-⍺) which mediates inflammation. Excessive TNF-⍺ contributes to death of endothelial cells (EC) with subsequent disruption of vascular endothelial function. Exchange Factor Directly Activated by cAMP (EPAC1) is a cyclic-AMP (cAMP) sensor that regulates multiple EC functions. We hypothesized that EPAC1 activation affects the response of EC to TNF-a. Microvascular EC were pretreated for 45 minutes with 100 mM 8-pCPT-2′-O-Me-cAMP (8-CPT, specific EPAC1 activator) or 10 mM forskolin (adenylyl cyclase activator that increases cAMP), then exposed to ...

Bis-Cinnamamide Derivatives As Ape/Ref-1 Inhibitors For The Treatment Of Human Melanoma, Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlain, Keykavous Parang, Sun Yang

Pharmacy Faculty Articles and Research

Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed. We ...