Cell and Developmental Biology Commons^™

Investigating Smooth Muscle Myosin Dynamics And Assembly In Physiology And Pathology, Maggie Bennett

Dissertations

Vascular smooth muscle cells (SMCs) surround many blood vessels throughout the body,where they dynamically alter vessel diameter to regulate blood pressure, provide structural integrity, and absorb shock on a beat-to-beat timescale. As smooth muscle function fails, profound vascular disease ensues, often with tragic results- even death. Smooth muscle myosin 2 (SM2) is the dominant motor protein that actuates contractility and allows SMCs to perform these vital functions. To function, SM2 monomers dynamically assemble into filaments, which upon SMC activation, associate with filamentous actin to drive contractility. Despite the critical contribution of SM2 to SMC function, foundational aspects of SM2 assembly …

Assessing The Roles Of Myc And Egr1 In Endoderm Differentiation, Sadaf R. Shahebrahimi, Joseph Nguyen, Kyra Skye Thomas, Erick Spears

Science University Research Symposium (SURS)

The Wnt signaling pathway is evolutionarily conserved from fruit flies to humans. Strongly associated with development and embryonic morphogenesis, it is known to be required for early endoderm and later hindgut development in mammals. In adults, the Wnt signaling pathway is required for the proper maintenance of the intestinal epithelium and mutations in critical Wnt signaling pathway components are initiating events in the development of essentially all colorectal cancers. An important target gene whose expression is upregulated by Wnt signaling pathway activation is the oncogene MYC. This gene produces a transcription factor whose typical cellular role is to stimulate …

Testing Ssa4:Ade3 Reporters For Mcs Screening, Karah Edmonds, Rebecca Adams

Science University Research Symposium (SURS)

In eukaryotic cells, after transcription, mRNA is escorted from the nucleus to the cytoplasm to be translated. This process, called mRNA export, is essential for gene expression. However, when the cell exists in stressful conditions, mRNA export becomes regulated, and only select transcripts, including the stress-responsive SSA4 mRNA, can be exported. This project aims to uncover the mechanism of selective SSA4 mRNA export by generating a reporter that enables phenotypically visible expression under stressful conditions. Specifically, the ADE3 ORF was placed under the regulatory sequence of SSA4, which was anticipated to induce a red color for colonies only following stress. …

Epigenetic Regulation Of Insect Development, Yaoyu Jiao

Theses and Dissertations--Entomology

Insects undergo a series of distinct life stages such as egg, larva and pupa to develop into mature adults capable of reproduction throughout their life cycle. In the larval stage, insects experience the fastest growth with voracious feeding and multiple cuticle shedding resulting in hundreds-of-fold increasing of size. During metamorphosis, insects stop increasing body size but go through dramatic tissue transformation, developing wings and other adult features. The characteristic mode of insect development, especially the metamorphosis, makes insects the most successful group of animals on the earth. However, the epigenetic mechanisms behind insect development remain elusive. Studying the epigenetic regulation …

Parental Instincts: The Neurological And Biological Factors Associated With Parenthood, Jared Reeder

Undergraduate Honors Theses

The following project involves a systematic review of the scientific literature on neural and biological changes of mothers and fathers in parenthood. Until very recently, little scientific research was devoted to studying how bearing children affects a man or woman’s long-term biology. Over the last twenty years, studies of neuroplastic changes in new mothers show specific neural mechanisms responsible for altering the behaviors of mothers during and after pregnancy. These changes in neuroplasticity alter behavior in such a way that led to mothers requiring less sleep and being more prone to hearing the cries of their children. In addition to …

Measuring How Kinetochore-Microtubule Detachment Contributes To Chromosome Movement And The Correction Of Attachment Errors, Melissa K. Parks

Dartmouth College Ph.D Dissertations

The goal of mitosis is to achieve faithful chromosome segregation; ensuring that the daughter cells inherit equal numbers of chromosomes. This is vital to cell health and viability and if mis-regulated can result in birth defects and disease such as cancer. There are many intricately regulated processes that occur throughout mitosis to achieve proper chromosome segregation, and one such example is the dynamic attachments formed between cytoskeletal structures, known as microtubules, and chromosomes, the carriers of genetic material. These attachments occur at structures called kinetochores, and the microtubules attached here are referred to as kinetochore-microtubules (k-MTs). These k-MTs are inherently …

The Effect Of E-Cigarette Vape On Oral Cell Proliferation Using 3d Spheroids As A Preclinical Model, Vikram Chinnaiyan

Honors Undergraduate Theses

E-cigarettes have recently become increasingly popular, especially amongst middle and high school students. Although they are marketed as safer alternatives to tobacco cigarettes, they produce toxic metals and carcinogenic nitrosamines. This thesis studies the effects of e-cigarette aerosol on the growth and proliferation of oral epithelial cells because the consequences of vaping, including a potential risk for aberrant growth leading to cancer, are not well understood. Cells were grown in matrigel, causing the formation of three-dimensional spheroids modeling the physiological architecture of the oral epithelium. Those spheroids were chronically exposed to vape with different treatment conditions to study the functional …

Combined 3d Bioprinting And Tissue-Specific Ecm System Reveals The Influence Of Brain Matrix On Stem Cell Differentiation, Martina Zamponi, Peter A. Mollica, Yara Khodour, Julie S. Bjerring, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures …

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood

Bioelectrics Publications

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and …

The Effect Of Larval Competition On Adult Life History Traits And The Immune Response Of Adult Cat Fleas (Ctenocephalides Felis), Piper N. Zellner, Lisa D. Brown

Honors College Theses

In holometabolous insects, conditions during the larval stage can affect the adult stage. For instance, in mosquitoes, reduced larval food and high density can make adults more susceptible to infection. Fleas (Siphonaptera), like mosquitoes, go through complete metamorphosis and have adult stages that exclusively feed on the blood of vertebrates, including humans. However, flea larvae have chewing mandibles and rely on nutrients from dried fecal matter containing vertebrate blood proteins. Their limited mobility and unique nutritional needs confine their development to specific areas, likely leading to frequent larval competition in natural conditions. Yet, the influence of larval density on the …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Characterization Of Parp1-Dependent Poly-Adp-Ribosylation Of Sprtn, Quincee Simonson

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) are a type of DNA lesion that form when proteins become covalently linked to DNA. It is estimated that replicating cells experience approximately 6,000 DPCs per day per genome during exponential growth (Ruggiano & Ramadan, 2021). If left unrepaired, DPCs can be lethal to cells. For this reason, cells have evolved multiple pathways to repair or bypass DPCs to survive. One such pathway involves SPRTN, a nuclear metalloprotease that plays a key role in the repair of DPCs through direct proteolysis (Lopez-Mosqueda et al., 2016; Vaz et al., 2016). Once SPRTN degrades the bulky protein component of …

Characterizing The Developmental Role Of Autism-Risk Gene Adnp In A Zebrafish Model For Autism, Vaishnavi Balaji

Master's Theses

Autism spectrum disorder is a complex neurodevelopmental disorder characterized by impaired social

skills, restricted/ repetitive behaviors, and developmental delay. The disease has a genetic component,

and mutations in the adnp gene have been found in 0.17% of non-inherited genetic cases of the disorder. The exact molecular mechanism by which adnp is involved in the development of autism is not known. This study aimed to use zebrafish to determine the phenotypic effects of adnp mutations using two adnp paralogs- adnpA and adnpB to understand the underlying mechanism. Novel zygotic adnp double heterozygous mutants (A+/- B+/-) were previously generated using …

Understanding The Role Of Peroxiredoxin Iv In Colorectal Cancer Development, Pratik Thapa

Theses and Dissertations--Toxicology and Cancer Biology

Reactive oxygen species (ROS) are oxygen-containing free radicals and/or molecules that are more reactive than O₂. ROS such as hydroxyl radical (•OH) and hydrogen peroxide (H₂O₂) are produced naturally in the body as a result of reactions such as aerobic respiration and oxidative protein folding. ROS undergo reduction-oxidation (redox) reactions and mediate cell signaling. Accumulation of excessive ROS can damage DNA, RNA, protein and lipids. Antioxidants are enzymes and small molecules that react with ROS to modulate redox signaling and to prevent and repair oxidative damage. Examples of antioxidants include glutathione, thioredoxin, superoxide dismutase, …

Targeting Ezh2 To Improve Outcomes Of Lung Squamous Cell Carcinoma, Tanner Ducote

Theses and Dissertations--Toxicology and Cancer Biology

Only 20% of patients diagnosed with lung squamous cell carcinoma (LSCC) respond to immunotherapy. Anti-PD1 immunotherapy is most commonly prescribed to these patients; however, most will become refractory. It is important to understand the mechanisms underlying this problem to increase durability and survival. Building upon the work of other groups, our lab has demonstrated that the inhibition of the histone methyltransferase, EZH2, is crucial to maintaining an immunologically responsive microenvironment. Based on our data, we hypothesize that combining EZH2 inhibitors with anti-PD1 therapy will increase response and durability. To study non-small cell lung cancers (NSLC) our lab uses a variety …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee

Dartmouth College Ph.D Dissertations

Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (⁹⁰Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …