Cell and Developmental Biology Commons^™

Erecta Family Genes Regulate The Shoot Apical Meristem And Organ Formation, Daniel A. Degennaro

Doctoral Dissertations

Plants are sessile and must adjust their organ growth to their environments. A reservoir of stem cells in the shoot apical meristem (SAM) supplies cells for differentiation into organs. The SAM must balance organ production with stem cell maintenance. The ERECTA family (ERfs) encodes the leucine-rich repeat receptor-like kinases ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERL2. ERf signaling regulates organ initiation and stem cell maintenance. Results presented in this work include the following:

1) WUSCHEL (WUS) and CLAVATA3 (CLV3) make up a negative feedback loop to maintain SAM size. WUS and CLV3 expression localization is critical for …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Regulatory Non-Coding Rnas Modulate Transcriptional Activation During B Cell Development, Mary Attaway, Tzippora Chwat-Edelstein, Bao Q. Vuong

Publications and Research

B cells play a significant role in the adaptive immune response by secreting immunoglobulins that can recognize and neutralize foreign antigens. They develop from hematopoietic stem cells, which also give rise to other types of blood cells, such as monocytes, neutrophils, and T cells, wherein specific transcriptional programs define the commitment and subsequent development of these different cell lineages. A number of transcription factors, such as PU.1, E2A, Pax5, and FOXO1, drive B cell development. Mounting evidence demonstrates that non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), modulate the expression of these transcription factors directly by binding …

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is …

Determining The Primary Dna Substrates Of Shld2'S Ob-Fold Domains, Hari Patchigolla

Holster Scholar Projects

Failure to repair DNA double-stranded breaks leads to cell death. Radiation therapy is commonly used to kill cancer cells by inducing these breaks. However resistance to radiation therapy, due to a hyperactive DNA double-stranded break repair pathway, is a common occurrence that makes cancer patients more prone to relapse. The Shieldin complex is shown to promote DNA-double stranded break repair by binding to DNA at sites of damage. Thus, the objective of this project is to understand the affinity and type of DNA that Shieldin binds to, through gel-shift assays, for the eventual creation of an inhibitor for this protein …

Using Molecular Diagnostics To Develop Therapeutic Strategies For Carbapenem-Resistant Gram-Negative Infections, Fred C. Tenover

Biology Faculty Publications

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly …

Phenotypic/Genotypic Profile Of Oxa-10-Like-Harboring, Carbapenem-Resistant Pseudomonas Aeruginosa: Using Validated Pharmacokinetic/Pharmacodynamic In Vivo Models To Further Evaluate Enzyme Functionality And Clinical Implications, Fred C. Tenover, Christian M. Gill, Adrian Brink, Chun Yat Chu, Jennifer Coetzee, George Dimopoulos, Clinton Moodley, Christoffel Johannes Opperman, Spyros Pournaras, Isabella A. Tickler, Hafsah Deepa Tootla, Sophia Vourli, David P. Nicolau

Biology Faculty Publications

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of β-lactamase variants.

Unbiased Automated Quantitation Of Ros Signals In Live Retinal Neurons Of Drosophila Using Fiji/Imagej, Prajakta Deshpande, Neha Gogia, Anuradha Venkatakrishnan Chimata, Amit Singh

Biology Faculty Publications

Numerous imaging modules are utilized to study changes that occur during cellular processes. Besides qualitative (immunohistochemical) or semiquantitative (Western blot) approaches, direct quantitation method(s) for detecting and analyzing signal intensities for disease(s) biomarkers are lacking. Thus, there is a need to develop method(s) to quantitate specific signals and eliminate noise during live tissue imaging. An increase in reactive oxygen species (ROS) such as superoxide (O2•-) radicals results in oxidative damage of biomolecules, which leads to oxidative stress. This can be detected by dihydroethidium staining in live tissue(s), which does not rely on fixation and helps prevent stress on tissues. However, …

Understanding The Novel Role Of Checkpoint Protein Rough Deal In Homolog Orientation And Centromeric Cohesion In Drosophila Male Meiosis, Qiutao He

Doctoral Dissertations

Meiosis is a central mechanism in sexual reproduction, through which the diploid precursor cells in the germline produce haploid gametes. After fertilization, a new set of diploid genome forms in the offspring with the characteristics of mother and father. The faithful transmission of genetic material to next generation relies on the fidelity of chromosome segregation during meiosis. A variety of mechanisms regulate the chromosome segregations in meiosis, including homolog interaction, chromosome cohesion, and sister-chromatid orientation. In most eukaryotic organisms, homolog interactions are built by the formation of chiasmata resulted from crossovers, but it is absent in male Drosophila in which …

Effects Of Trans-Acting Factors On The Translational Machinery In Yeast, Brandon M. Trainor

Graduate School of Biomedical Sciences Theses and Dissertations

Synthesis of proteins, or translation, is a complex biological process requiring the coordinated effort of numerous protein and RNA factors. Central to translation is the ribosome, a complex macromolecular complex consisting of both ribosomal RNA (rRNA) and ribosomal protein (r-protein). Ribosomes are essential and are one of the oldest and most abundant biomolecules across all forms of life. In addition to the ribosome, translation requires messenger RNA (mRNA), transfer-RNA conjugated to an amino acid (aa-tRNA), translation factors, and energy in the form of ATP and GTP. Translation universally occurs in four major stages, initiation, elongation, termination, and recycling, with initiation …

Npsd4: A New Player In Sumo-Dependent Dna Repair, Erin Atkinson

Dissertations & Theses (Open Access)

The human genome is under constant threat from sources of damage and stress. Improper resolution of DNA damage lesions can lead to mutations, oncogene activation, and genomic instability. Difficult-to-replicate-loci present barriers to DNA replication that, when not properly resolved, lead to replication fork stalling and collapse and genomic instability.

DNA damage and replication stress trigger signaling cascades potentiated by multiple types of post-translational modifications, including SUMOylation. Through proteomic analysis of proteins involved in SUMOylation following DNA damage, our lab identified an uncharacterized protein that we named New Player in SUMO-dependent DNA damage repair 4 (NPSD4). Through an additional proteomic screen, …

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations & Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

Targeting Plasma Membrane Phosphatidylserine Content To Inhibit Oncogenic Kras Function, Walaa E. Kattan

Dissertations & Theses (Open Access)

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We therefore investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidylinositol-4-phosphate (PI4P) synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion …

Epithelial Memory Of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis, I-Lin Ho

Dissertations & Theses (Open Access)

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma. When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Analysis Of Differential Gene Expression Patterns During Spiral Intestine Development In Leucoraja Erinacea, Kelsey Cox

Honors Theses

The vertebrate gut is a specialized structure responsible for the intake and digestion of food, absorption of nutrients, and expulsion of waste products. The organs of the digestive tract have been conserved over time, but modifications to the size and shape of individual structures exist within the different vertebrate lineages. The skate’s spiral intestine has evolved to maximize nutrient absorption within a compact structure to create space in the body cavity for the organs needed for buoyancy. Studying the unique intestinal morphology of Leucoraja erinacea, or the little skate, provides an opportunity to understand the role of differential gene expression …

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …

Creating A Protein Chimera To Study Regulation Of Muscle Diversity, Shannon Scarboro

Symposium of Student Scholars

Creating a protein chimera to study regulation of muscle diversity.

Body muscles are made of many individual super-cells, called muscle fibers, that have distinct properties and determine every individual’s strength and endurance. Initially all muscle fibers have identical characteristics, but become differentiated into specific types in adults. The mechanism of such transition is not well understood, despite its obvious importance for shaping human physicality.

Remarkable conservation of the muscle tissue enables us to use fruit flies to study the mechanisms of muscle fiber diversity. We hypothesized that the transcription factor Mef2 acts as a molecular switch that activates structural genes …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Translational Fidelity And Its Role In Neuronal Homeostasis, Markus Terrey

Electronic Theses and Dissertations

The process of translation, which refers to decoding genetic information from mRNA to protein, is vital for all cellular function. Translational fidelity starts at the level of aminoacylation of transfer RNAs (tRNA). This reaction is catalyzed by aminoacyl tRNA synthetases where each amino acid is transferred to its corresponding cognate tRNA. Because tRNAs harbor the anticodon sequence to decodes a particular mRNA codon, the specific aminoacylation of the tRNA with a cognate amino acid establishes the rules of decoding genetic code into proteins. Aminoacylated tRNAs are then delivered to ribosomes, where ribosomes in a highly organized manner need to accurately …

The Analysis Of Folate-Dependent Transcription Factor Zinc Finger Protein 410, Feifan Xu

Senior Honors Theses

A previous study that introduced dietary folate to mice in the form of folic acid to determine if gene activity would be altered based on this biological molecule demonstrated that mice without folic acid had cognition deficits, and this phenomenon was correlated with altered gene expression in their brains. The included bioinformatic analysis revealed two main transcription factors that bind to proteins in the nucleus, and one is known as the Zinc Finger Protein 410 (Zfp410). Due to the lack of literature explaining the function of this transcription factor, this project is intended to analyze Zfp410 in detail from scratch. …

Zebrafish (Danio Rerio) Hoxb6: An Exploration Into The Divergence Of Genomic Dna Sequence And Gene Expression Across Teleost Fishes Post-Genome Duplication, Amber Lynn Rittgers, Pierre Le Pabic, Adam Davis

Georgia Journal of Science

Hoxb6 is an evolutionarily conserved developmental regulatory gene that functions, in part, to pattern several organs and organ systems within the embryonic trunk during vertebrate embryogenesis. The cis-regulatory circuitry mediating trunk expression in mouse (Mus musculus) may be conserved across gnathostome vertebrates, as several other species show similar trunk expression patterns, including chicken (Gallus gallus), dogfish shark (Scyliorhinus canicula), and several teleost fishes. A whole genome duplication event that occurred in the lineage leading to teleost fishes has generated at least two Hoxb6 genes, hoxb6a and b6b. Two teleost fishes of the …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

Expression And Function Of Transcription Factors Foxa1, Hoxb13 And Cdx2 In Prostate Cancer, Hamsat B. Anwar

University Honors Theses

Prostate cancer (PC) is the second leading cause of death in men, affecting around 190 thousand patients in 2020 alone (National Institute of Cancer, 2020). Much of the current research focuses on treatments for advanced PC, which is problematic due to the rapid evolution of tumors and development of treatment resistance. Cancer early detection presents a better approach to control and treat patients before they acquire an incurable disease. Earlier diagnosis of patients leads to better prognosis and a more comfortable treatment process (Etzioni et al., 2003). However, we currently lack molecular markers to stratify PC during its early stages. …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9/Syntenin, Jinkal Modi, Anjan Pradhan, Luni Emdad, Swadesh Das, Paul Fisher

Graduate Research Posters

Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify a new non-angiogenesis-dependent pathway vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like network, such as plasma and red blood cells. The co-generation of endothelial …

Transactivation And Mitochondrial Activity Are Affected By High Temperature In C. Elegans Sperm, Jacqueline Mcvay

Scripps Senior Theses

Sexual reproduction has a conserved flaw in that it is temperature sensitive. Exposure to high temperature leads to male infertility, but little is known about the underlying mechanism. Understanding these mechanisms is important for agriculture and reproductive medicine. Using C. elegans, we investigated two potential aspects of male fertility that may be affected by high temperature conditions: activation of sperm by seminal fluid and sperm mitochondrial activity. There are two pathways for sperm activation in C. elegans: the SPE-8 pathway in hermaphrodites and the TRY-5 pathway in male seminal fluid. Hermaphrodite sperm with a mutation in spe-8 can …