Cell and Developmental Biology Commons^™

Lof1 And Interacting Transcription Factors In Plant Development And Crop Yield, Zoe Yeoh, Elizabeth Luscher, Patricia Springer

Student Publications

Transcription factors (TFs) help ensure proper gene expression in developing tissues, and thus play a role in plant development and plant architecture. LATERAL ORGAN FUSION1, or LOF1, is a TF expressed in the organ boundaries of Arabidopsis thaliana. lof1 mutants have fused axillary branches and cauline leaves, which indicates importance in boundary development. Because transcription factors are known to act in complexes, we wanted to discover what other proteins interact with LOF1. We executed a yeast-2-hybrid (Y2H) screen that identified several TFs as potential interactors: WHIRLY 3 (WHY3), MYB DOMAIN PROTEIN32 (MYB32), HOMEOBOX-LEUCINE ZIPPER PROTEIN4 (HB4), and LIGHT RESPONSE BTB2 …

Selfish Mutations: The Genetic Basis Of The Paternal Age Effect, Eoin C. Whelan

Biological Sciences Theses & Dissertations

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring.

I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain …

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity Via Interferon-Beta And Indoleamine-2,3-Dioxygenase, Michael B. Cheung

USF Tampa Graduate Theses and Dissertations

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in young children worldwide, accounting for an estimated 33.8 million cases of respiratory disease, over 3 million of which require hospitalization, and between 66,000 and 199,000 deaths in this susceptible population. Additionally, severe RSV infection early in life is associated with an increased risk of wheeze and other airway disorders later in life. Despite this, there is currently no vaccine or economically reasonable prophylactic regimen to prevent infection. While disease is typically more severe in infancy RSV can infect throughout the lifespan repeatedly as the …

Cell Cycle Arrest By Tgfß1 Is Dependent On The Inhibition Of Cmg Helicase Assembly And Activation, Brook Samuel Nepon-Sixt

USF Tampa Graduate Theses and Dissertations

Tumorigenesis is a multifaceted set of events consisting of the deregulation of several cell-autonomous and tissue microenvironmental processes that ultimately leads to the acquisition of malignant disease. Transforming growth factor beta (TGFß) and its family members are regulatory cytokines that function to ensure proper organismal development and the maintenance of homeostasis by controlling cellular differentiation, proliferation, adhesion, and survival, as well as by modulating components of the cellular microenvironment and immune system. The pleiotropic control by TGFß of these cell intrinsic and extrinsic factors is intimately linked to the prevention of tumor formation, the specifics of which are dependent on …

Determination Of Glut1 Oligomerization Parameters Using Bioluminescent Förster Resonance Energy Transfer, Brendan D. Looyenga, Calvin Vanopstall, Zion Lee, Jed Bell

University Faculty Publications and Creative Works

The facilitated glucose transporter GLUT1 (SLC2A1) is an important mediator of glucose homeostasis in humans. Though it is found in most cell types to some extent, the level of GLUT1 expression across different cell types can vary dramatically. Prior studies in erythrocytes - which express particularly high levels of GLUT1 - have suggested that GLUT1 is able to form tetrameric complexes with enhanced transport activity. Whether dynamic aggregation of GLUT1 also occurs in cell types with more modest expression of GLUT1, however, is unclear. To address this question, we developed a genetically encoded bioluminescent Förster resonance energy transfer (BRET) assay …

Anticancer Activities Of Resveratrol In Colorectal Cancer, Evelien Schaafsma, Tze-Chen Hsieh, Barbara B. Doonan, John T. Pinto, Joseph M. Wu

NYMC Faculty Publications

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a dietary polyphenolic phytochemical that has demonstrated health benefits such as cardioprotection, the prevention of neurodegeneration and chemoprevention. Resveratrol has shown great potential in the prevention and treatment of carcinomas and clinical trials support resveratrol as anticancer compound in colorectal carcinoma. Colorectal cancer remains a major cause of cancer-related deaths for both men and women in industrialized countries. Because of this widespread prevalence, identifying major risk factors and initiating colorectal screening procedures provide the distinct advantage for recognizing early disease and addressing treatable forms of CRC. Epidemiological studies of fruit and vegetable consumption in relationship to developing …

Staphylococcus Aureus Coordinates Leukocidin Expression And Pathogenesis By Sensing Metabolic Fluxes Via Rpirc, Divya Balasubramanian, Elizabeth A Ohneck, Jessica Chapman, Andy Weiss, Min Kyung Kim, Tamara Reyes-Robles, Judy Zhong, Lindsey N. Shaw, Desmond S. Lun, Beatrix Ueberheide, Bo Shopsin, Victor J Torres

Molecular Biosciences Faculty Publications

Staphylococcus aureus is a formidable human pathogen that uses secreted cytolytic factors to injure immune cells and promote infection of its host. Of these proteins, the bicomponent family of pore-forming leukocidins play critical roles in S. aureus pathogenesis. The regulatory mechanisms governing the expression of these toxins are incompletely defined. In this work, we performed a screen to identify transcriptional regulators involved in leukocidin expression in S. aureus strain USA300. We discovered that a metabolic sensor-regulator, RpiRc, is a potent and selective repressor of two leukocidins, LukED and LukSF-PV. Whole-genome transcriptomics, S. aureus exoprotein proteomics, and metabolomic analyses revealed that …

Loss Of Cell Adhesion Increases Tumorigenic Potential Of Polarity Deficient Scribble Mutant Cells, Indrayani Waghmare, Madhuri Kango-Singh

Biology Faculty Publications

Epithelial polarity genes are important for maintaining tissue architecture, and regulating growth. The Drosophila neoplastic tumor suppressor gene scribble (scrib) belongs to the basolateral polarity complex. Loss of scrib results in disruption of its growth regulatory functions, and downregulation or mislocalization of Scrib is correlated to tumor growth. Somatic scribble mutant cells (scrib-) surrounded by wild-type cells undergo apoptosis, which can be prevented by introduction of secondary mutations that provide a growth advantage. Using genetic tools in Drosophila, we analyzed the phenotypic effects of loss of scrib in different growth promoting backgrounds. We investigated if a central …

Dynamic Surfaces For The Study Of Mesenchymal Stem Cell Growth Through Adhesion Regulation, Jemma N. Roberts, Jugal Kishore Sahoo, Laura E. Mcnamara, Karl V. Burgess, Jingli Yang, Enateri V. Alakpa, Hilary J. Anderson, Jake Hay, Lesley-Anne Turner, Stephen J. Yarwood, Mischa Zelzer, Richard O.C. Oreffo, Rein V. Ulijn, Matthew J. Dalby

Advanced Science Research Center

Out of their niche environment, adult stem cells, such as mesenchymal stem cells (MSCs), spontaneously differentiate. This makes both studying these important regenerative cells and growing large numbers of stem cells for clinical use challenging. Traditional cell culture techniques have fallen short of meeting this challenge, but materials science offers hope. In this study, we have used emerging rules of managing adhesion/ cytoskeletal balance to prolong MSC cultures by fabricating controllable nanoscale cell interfaces using immobilized peptides that may be enzymatically activated to change their function. The surfaces can be altered (activated) at will to tip adhesion/cytoskeletal balance and initiate …

Nfat5/Stat3 Interaction Mediates Synergism Of High Salt With Il-17 Towards Induction Of Vegf-A Expression In Breast Cancer Cells, Suneetha Amara, Dalal Alotaibi, Venkataswarup Tiriveedhi

Biology Faculty Research

Chronic inflammation has been considered an important player in cancer proliferation and progression. High salt (sodium chloride) levels have been considered a potent inducer of chronic inflammation. In the present study, the synergistic role of high salt with interleukin (IL)‑17 towards induction of the inflammatory and angiogenic stress factor vascular endothelial growth factor (VEGF)‑A was investigated. Stimulation of MCF-7 breast cancer cells with high salt (0.2 M NaCl) and sub‑minimal IL‑17 (1 ng/ml) enhanced the expression of VEGF-A (2.9 and 2.6-fold, respectively, P<0.05) compared with untreated cells. Furthermore, co‑treatment with both high salt and sub‑minimal IL‑17 led to a 5.9‑fold increase in VEGF‑A expression (P<0.01), thus suggesting a synergistic role of these factors. VEGF‑A promoter analysis and specific small interfering RNA knock‑down of transcription factors revealed that high salt induced VEGF‑A expression through nuclear factor of activated T‑cells (NFAT)5, while IL‑17 induced VEGF‑A expression via signal transducer and activator of transcription (STAT)3 signaling mechanisms. Treatment of normal human aortic endothelial cells with the supernatant of activated MCF‑7 cells enhanced cell migration and induced expression of migration‑specific factors, including vascular cell adhesion protein, β1 integrin and cluster of differentiation 31. These data suggest that high salt levels synergize with pro‑inflammatory IL‑17 to potentially induce cancer progression and metastasis through VEGF‑A expression. Therefore, low‑salt diet, anti‑NFAT5 and anti‑STAT3 therapies may provide novel avenues for enhanced efficiency of the current cancer therapy.

Intronic Cleavage And Polyadenylation Regulates Gene Expression During Dna Damage Response Through U1 Snrna, Emral Devany, Ji Yeon Park, Michael R. Murphy, George Zakusilo, Jorge Baquero, Xiaokan Zhang, Mainul Hoque, Bin Tian, Frida E. Kleiman

Publications and Research

The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3ʹ untranslated region is substantial, leading to both shortening and lengthening of 3ʹ untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5ʹ end of genes and affect gene groups with important functions in DNA damage …

Hexavalent Chromium Induces Malignant Transformation Of Human Lung Bronchial Epithelial Cells Via Ros-Dependent Activation Of Mir-21-Pdcd4 Signaling, Poyil Pratheeshkumar, Young-Ok Son, Sasidharan Padmaja Divya, Lilia Turcios, Ram Vinod Roy, John Andrew Hitron, Lei Wang, Donghern Kim, Jin Dai, Padmaja Asha, Zhuo Zhang, Xianglin Shi

Center for Research on Environmental Disease Faculty Publications

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with an increased risk of lung cancer. However, the mechanisms underlying Cr(VI)-induced carcinogenesis remain unclear. MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. Studies have shown that miR-21 exerts its oncogenic activity by targeting the tumor suppressor gene programmed cell death 4 (PDCD4). The present study examined the role of miR-21-PDCD4 signaling in Cr(VI)-induced cell transformation and tumorigenesis. Results showed that Cr(VI) induces ROS generation in human bronchial epithelial (BEAS-2B) cells. Chronic exposure to Cr(VI) is able to cause malignant transformation in BEAS-2B cells. Cr(VI) caused a significant increase of …

Klf4 Deletion Alters Gastric Cell Lineage And Induces Muc2 Expression, Tianxin Yu, Xi Chen, T. Lin, J. Liu, M. Li, W. Zhang, X. Xu, W. Zhao, M. Liu, Dana L. Napier, Chi Wang, B. Mark Evers, Chunming Liu

Markey Cancer Center Faculty Publications

Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4^fl/fl and Lgr5-Cre;Klf4^fl/fl. KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous …

Semaphorin3a Increases Focal Adhesion Formation To Shift The Relationship Between Cell Migration And Substratum Concentration Through A Rock-Dependent Mechanism, Frances V. Compere, Scott Gehler

Celebration of Learning

Cell migration is essential for many life processes, including wound healing, embryonic development and cancer metastasis. Cells move across a surface by interacting and forming adhesions with the molecules in their environment, specifically the extracellular matrix. Past studies have shown that there is an optimal level of cell-substratum adhesive strength that allows for the most cell migration and spreading (DiMilla et al., 1993; Gaudet et al., 2003). The mechanism by which this works is not well understood, however. Semaphorin 3A (Sema3A) has been shown to increase the expression of integrin receptors, which help mediate the formation of the adhesions between …

Cmg Helicase Assembly And Activation: Regulation By C-Myc Through Chromatin Decondensation And Novel Therapeutic Avenues For Cancer Treatment, Victoria Bryant

USF Tampa Graduate Theses and Dissertations

The CMG (Cdc45, MCM, GINS) helicase is required for cellular proliferation and functions to unwind double-stranded DNA to allow the replication machinery to duplicate the genome. Cancer cells mismanage helicase activation through a variety of mechanisms, leading to the potential for the development of novel anti-cancer treatments. Mammalian cells load an excess of MCM complexes that act as reserves for new replication origins to be created when replication forks stall due to stress conditions, such as drug treatment. Targeting the helicase through inhibition of the MCM complex has sensitized cancer cells to drugs that inhibit DNA replication, such as aphidicolin …

Mof Acetylates The Histone Demethylase Lsd1 To Suppress Epithelial-To-Mesenchymal Transition., Huacheng Luo, Anitha K Shenoy, Xuehui Li, Yue Jin, Lihua Jin, Edward Seto, +10 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby …

Human Glia Can Both Induce And Rescue Aspects Of Disease Phenotype In Huntington Disease, Abdellatif Benraiss, Su Wang, Stephanie Herrlinger, Xiaojie Li, Devin Chandler-Militello, Jian Kang, Steven Goldman, Martha S. Windrem, Ignacio Munoz-Sanjuan, Maiken Nedergaard, Steven A. Goldman

NYMC Faculty Publications

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, …

Genetic Analysis Reveals A Hierarchy Of Interactions Between Polycystin-Encoding Genes And Genes Controlling Cilia Function During Left-Right Determination, Daniel T. Grimes, Jennifer L. Keynton, Maria T. Buenavista, Xingjian Jin, Saloni H. Patel, Shinohara Kyosuke, Jennifer Vibert, Debbie J. Williams, Hiroshi Hamada, Rohana Hussain, Surya M. Nauli, Dominic P. Norris

Pharmacy Faculty Articles and Research

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca²⁺ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we …

Trypanosoma Brucei Tif2 And Trf Suppress Vsg Switching Using Overlapping And Independent Mechanisms, Sanaa E. Jehi, Vishal Nanavaty, Bibo Li Ph.D.

Biological, Geological, and Environmental Faculty Publications

Trypanosoma brucei causes debilitating human African trypanosomiasis and evades the host's immune response by regularly switching its major surface antigen, VSG, which is expressed exclusively from subtelomeric loci. We previously showed that two interacting telomere proteins, TbTRF and TbTIF2, are essential for cell proliferation and suppress VSG switching by inhibiting DNA recombination events involving the whole active VSG expression site. We now find that TbTIF2 stabilizes TbTRF protein levels by inhibiting their degradation by the 26S proteasome, indicating that decreased TbTRF protein levels in TbTIF2-depleted cells contribute to more frequent VSG switching and eventual cell growth arrest. Surprisingly, although TbTIF2 …

Identification Of Genes That Are Essential To Restrict Genome Duplication To Once Per Cell Division., Alex Vassilev, Chrissie Y. Lee, Boris Vassilev, Wenge Zhu, Pinar Ormanoglu, Scott E. Martin, Melvin L. Depamphilis

Biochemistry and Molecular Medicine Faculty Publications

Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53- cells to reveal the relevance of this ubiquitous tumor suppressor …

Inflammatory Bowel Disease, Colorectal Cancer And Type 2 Diabetes Mellitus: The Links., Abdo Jurjus, Assad Eid, Sahar Al Kattar, Marie Noel Zeenny, Alice Gerges-Geagea, Rosalyn A. Jurjus, +10 Additional Authors

Anatomy and Regenerative Biology Faculty Publications

The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others. This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases. The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array …

Oncogenic Pik3ca Mutations Reprogram Glutamine Metabolism In Colorectal Cancer, Yujun Hao, Yardena Samuels, Qingling Li, Dawid Krokowski, Bo-Jhih Guan, Chao Wang, Zhicheng Jin, Bohan Dong, Bo Cao, Xiujing Feng, Min Xiang, Claire Xu, Stephen Fink, Neal J. Meropol, Yan Xu

Chemistry Faculty Publications

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not …

Oligodendrocyte Ablation As A Tool To Study Demyelinating Diseases, Ahdeah Pajoohesh-Ganji, Robert H. Miller

Anatomy and Regenerative Biology Faculty Publications

Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.

Generation Of Organ-Conditioned Media And Applications For Studying Organ-Specific Influences On Breast Cancer Metastatic Behavior, Matthew M. Piaseczny, Graciella M. Pio, Jenny E. Chu, Ying Xia, Kim Nguyen, David Goodale, Alison Allan

Anatomy and Cell Biology Publications

Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. …

Orrm6 Is A Novel Organellar Rna Recognition Protein Involved In Plastid Rna Editing In Arabidopsis Thaliana, Justin B. Hackett

Masters Theses

RNA editing is a conserved mechanism of post-transcriptional modification in eukaryotes that changes specific nucleotides in RNA transcripts. In flowering plants, this is limited to cytidine to uridine deaminations. Plastid RNA editing events are critical for plastid development and the loss of editing can result in untranslated or non-functional proteins. There have been 40 RNA editing events discovered in the Arabidopsis thaliana plastid. Recently organellar RNA recognition motif (ORRM) proteins have been shown to broadly affect plastid RNA editing and interact with sequence specific trans-factor pentatricopeptide repeat proteins (PPR). ORRM proteins contain a canonical RNA recognition motif that has been …

Characterization Of Nuclear Factor-Kappab Binding Sites In The Freshwater Snail, Biomphalaria Glabrata, Laura E. Deneckere

Lawrence University Honors Projects

Biomphalaria glabrata is an intermediate snail host for the digenean trematode, Schistosoma mansoni, which causes the human disease schistosomiasis. A lot of research has focused on the snail-schistosome interaction, especially in regards to the immune response of the snail. The nuclear factor-kappaB (NF-κB) pathway, which is involved in regulating the immune response, can be triggered by the Toll-like receptor (TLR) signaling pathway. However, not much is known about the specific molecular mechanisms regulating these responses. Both NF-κB and TLR homologues have recently been reported in B. glabrata so it is of great interest to determine if BgNF-κB can regulate …

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez

Electronic Theses, Projects, and Dissertations

Conventional medical treatments fail to address the underlying problems associated with the damage inflicted by a coronary event. Thus, the long-term prognosis of patients admitted for heart failure is disheartening, with reported survival rates of 25 percent. Recent advances in stem cell research highlight the potential benefits of autologous stem cell transplantation for stimulating repair in heart tissue. However, a majority of those suffering from cardiovascular diseases are older adults whose autologous cells no longer possess optimum functional capacity. Additional work is needed to identify the optimal cell types or conditions that will promote cardiovascular regeneration across all age groups. …

Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill

Electronic Theses, Projects, and Dissertations

Ovarian cancer is the fifth leading cause of cancer death in women between the ages of 35 and 74. With 22 thousand new cases and 15 thousand deaths annually ovarian cancer is among the most deadly cancers with a death to incidence ratio of 68%. With 70% of cases High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer and causes 90% of ovarian cancer deaths. 80% of patients have reoccurrence within five years and only 15-30% of patients with recurrent metastatic ovarian cancer respond to current therapies, chemotherapy and surgery. One reason for the high …

Melanocortin 1 Receptor: Structure, Function, And Regulation, Erin M. Wolf Horrell, Mary C. Boulanger, John A. D'Orazio

Physiology Faculty Publications

The melanocortin 1 receptor (MC1R) is a melanocytic G_s protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV …