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Articles 1 - 13 of 13
Full-Text Articles in Developmental Biology
Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley
Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley
Theses and Dissertations
Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …
Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales
Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales
Theses and Dissertations
Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …
Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer
Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer
Honors Scholar Theses
The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …
Understanding The Regulatory Context And Mechanism Of Hlh-25 Mediated Transcriptional Repression, Dagmawi Mamo
Understanding The Regulatory Context And Mechanism Of Hlh-25 Mediated Transcriptional Repression, Dagmawi Mamo
Masters Theses, 2020-current
The HES family of transcription factors are primarily repressors of transcription that play critical roles in mammalian embryogenesis by regulating cell differentiation and proliferation. Proper functioning of HES proteins is crucial in humans, as mutations or misexpression of HES1 is associated with lung, pancreas, colon, and other cancers. HES1 may mediate short-range or long-range repression through DNA-binding and or protein-protein interactions with other factors. However, prior genetic studies have not fully elucidated how the context-specific binding of HES1, or its C. elegans ortholog HLH-25, promotes the repression of transcription. Characterization of the cis-regulatory context and mechanism of HLH-25 mediated repression …
Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes
Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes
The Cardinal Edge
The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway …
Cop9 Signalosome Component Csn-5 Promotes Accumulation And Function Of Stem Cell Regulators Fbf-1 And Fbf-2, Emily Osterli
Cop9 Signalosome Component Csn-5 Promotes Accumulation And Function Of Stem Cell Regulators Fbf-1 And Fbf-2, Emily Osterli
Graduate Student Theses, Dissertations, & Professional Papers
RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for stem cell maintenance in C. elegans, although the mechanisms by which FBFs protein levels are regulated remain unknown. Using a yeast two-hybrid screen, we identified an interaction between both FBFs and CSN-5, a component of the COP9 (constitutive photomorphogenesis 9) signalosome. This highly conserved COP9 complex can affect protein stability through a range of mechanisms including deneddylation, deubiquitination, and phosphorylation (Wolf et al., 2003). Mapping protein-protein interactions between FBFs and CSN-5 suggested that the MPN (Mpr1/Pad1 N-terminal) metalloprotease domain of CSN-5 interacts with the RNA-binding domain of FBFs at physiologically …
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Dissertations and Theses (Open Access)
Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …
The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala
The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala
Dissertations, Theses, and Capstone Projects
All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in …
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
Electronic Theses and Dissertations
Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …
Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez
Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez
Dissertations and Theses (Open Access)
Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found …
Detection Of Ubiquitination On Syk And Documenting Syk Stability, Izabela Mazur, Wen Horng Wang, Robert J. Geahlen
Detection Of Ubiquitination On Syk And Documenting Syk Stability, Izabela Mazur, Wen Horng Wang, Robert J. Geahlen
The Summer Undergraduate Research Fellowship (SURF) Symposium
Post-translational modifications regulate the activities of proteins important to numerous diseases. Spleen Tyrosine Kinase (Syk) is particularly interesting to researchers because it modifies many targets and plays multiple roles in regulating cells in our bodies and its abnormal modifications may contribute to cancer, Alzheimer’s disease and allergies. In an attempt to study these modifications of Syk, we first looked at detecting ubiquitination on Syk protein. Ubiquitin, a small 8 kDa molecule, attaches to lysine residues on protein. The attachment of ubiquitin to Syk may cause Syk to either propagate signals onwards to activate other proteins or signal it to undergo …
Environmental Stimuli And Intragenerational Epigenetics, Nicholas J. Napier
Environmental Stimuli And Intragenerational Epigenetics, Nicholas J. Napier
Student Scholarship
Epigenetics is the study of any change in gene expression that is not mediated by DNA sequence. The effects of environmental stimuli on epigenetic changes have been studied extensively in recent years. Multiple reviews have provided comprehensive summations of the effects of environmental stimuli on transgenerational epigenetic changes, but few reviews have focused upon environment-induced intragenerational epigenetic changes. This review will summarize current knowledge of the intragenerational epigenetic changes that are induced by two groups of well-studied environmental stimuli: nutritional deficiencies and carcinogens. This survey of intragenerational epigenetic changes will focus upon the mechanisms behind them, the disorders associated with …
Developmental Deregulation And Tumorigenesis Inhibition In 14-3-3zeta Knockout Mouse, Jun Yang
Developmental Deregulation And Tumorigenesis Inhibition In 14-3-3zeta Knockout Mouse, Jun Yang
Dissertations and Theses (Open Access)
Cancer is second leading cause of death in the United States. Improving cancer care through patient care, research, education and prevention not only saves lives, but reduces health care cost as well. Breast cancer is the most leading cause of cancer incidence and cancer related death in women of the United States. 14-3-3s are a family of conserved proteins ubiquitously expressed in all eukaryotic organisms. They form complexes with hundreds of proteins by binding to specific phospho-serine/threonine containing motifs. In this way they regulate a variety of cellular processes and are involved in many human diseases especially cancer to our …