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Articles 31 - 60 of 277

Full-Text Articles in Cell and Developmental Biology

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner Feb 2024

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

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Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton Jan 2024

Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton

Dissertations and Theses

B cells excise and recombine the immunoglobulin heavy chain gene locus during class switch recombination (CSR). CSR is mediated by activation induced cytidine deaminase (AID) and results in a new immunoglobulin isotype that B cells will secrete and present. AID produces mutations that convert cytosines to uracils within the intronic switch regions that precede and follow the target immunoglobulin isotype coding sequence. To resolve the mutations, B cells conduct either base excision repair (BER) or mismatch repair (MMR). Inactivating genetic mutations in BER or MMR reduce CSR. For example, a knock-out of uracil DNA glycosylase (UNG) causes a 50% reduction …

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Synthesis Of Novel 5-Aryl 2’-Deoxyuridine And 2’-Deoxycytidine Analogues, Kevin E. Persaud Jan 2024

Synthesis Of Novel 5-Aryl 2’-Deoxyuridine And 2’-Deoxycytidine Analogues, Kevin E. Persaud

Dissertations and Theses

Briefly, the following report details a synthetic route to prepare 5-phenyl-2’-deoxycytidine analogues. This multistep synthesis began with silyl protection of the 3’- and 5’-hydroxyl groups of 5-iodo-2’-deoxyuridine. Next, the installation of a phenyl ring at the C5 position of the nucleobase via a Suzuki-Miyaura cross-coupling reaction, yielding 5-phenyl-2’-deoxyuridine (5-PdU). After that, modification of the obtained 5-PdU at the C4 position was performed with benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP, a peptide-coupling agent) and a base (cesium carbonate) to activate the amide group of the uridine nucleobase for subsequent displacement with a variety of amines. Modification of the C4 position resulted in protected 5-phenyl-2’-deoxycytidine …

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Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma Sep 2023

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

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Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem Sep 2023

Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that represents roughly 15% of all diagnosed breast cancers. TNBC is defined by the absence of expression of progesterone, estrogen, and human epidermal growth factor 2 receptors, and has a higher incidence rate in pre-menopausal women and women of African and of Hispanic ancestry. Due to the inability to target a receptor, treatment is limited to nonspecific chemotherapy or immunotherapy. Only one FDA approved therapy is available specifically to treat TNBC, which is antibody drug conjugate Sacitzumab-govitecan, given to patients who have already gone through two rounds of …

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Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu Sep 2023

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

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Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams Jun 2023

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …

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Examining Transcriptional Regulators During Muscle Development In Drosophila Melanogaster, Chaamy Yapa May 2023

Examining Transcriptional Regulators During Muscle Development In Drosophila Melanogaster, Chaamy Yapa

Student Theses and Dissertations

In Drosophila melanogaster embryos, a distinct approach to study the transcriptional regulation is to examine the larval somatic muscle development. Transcription factors are essential regulatory proteins that help to control gene expression and respond to signaling pathways and various cues. Today, there are at least twenty transcription factors that have been discovered to contribute to the development of the 30 distinct larval somatic muscles in each abdominal hemisegment of Drosophila melanogaster. Several studies have already been conducted on muscle regulatory transcription factors including midline and apterous. These transcription factors were shown to control the development of muscles through mutant …

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Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska May 2023

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

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The Effects Of Glycolytic Mutations In Drosophila Melanogaster Muscle Development, Coco Lim May 2023

The Effects Of Glycolytic Mutations In Drosophila Melanogaster Muscle Development, Coco Lim

Student Theses and Dissertations

Muscle atrophy, or muscle wasting, is caused due to lack of physical activity for an extended period of time, due to muscle diseases (such as muscle dystrophies), cancer chemotherapies, and aging. It is also extensively found on astronauts after spaceflight, particularly missions of long durations. Muscle cells are dependent on different metabolic pathways to optimize Adenosine triphosphate (ATP) production to compensate for muscle exertion. Glycolysis converts glucose into ATP producing pyruvate, which can be sent into the citric acid cycle or converted to lactate (lactic acid). Muscles preferentially use lactate production, despite the fact that fewer molecules of ATP are …

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Auditory Processing Deficits In Msh2-Ko Mice Are Linked To Aberrant Inhibitory Neuron Function In The Thalamic Reticular Nucleus, Sadia N. Rahman Jan 2023

Auditory Processing Deficits In Msh2-Ko Mice Are Linked To Aberrant Inhibitory Neuron Function In The Thalamic Reticular Nucleus, Sadia N. Rahman

Dissertations and Theses

DNA repair mechanisms are crucial for both cellular development and function. One highly conserved DNA repair factor is Mut-S Homolog 2 (Msh2), which corrects base-base mismatches and insertion/deletion loops. In humans, defects in this repair pathway are linked to diseases that have severe neurological pathologies. These include Lynch syndrome, Huntington’s disease and demyelination of the corpus callosum. The fundamental role of Msh2 in brain function is unknown. Using an Msh2-/- mouse model we began an exploration of its impact on the processing of sensory information, a crucial function to an animal’s survival. The goal of this …

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Mutant C. Elegans P53 Together With Gain-Of-Function Glp-1/Notch Decreases Uvc-Damage-Induced Germline Cell Death But Increases Parp Inhibitor-Induced Germline Cell Death, Jorge Canar, Prima Manandhar-Sasaki, Jill Bargonetti Oct 2022

Mutant C. Elegans P53 Together With Gain-Of-Function Glp-1/Notch Decreases Uvc-Damage-Induced Germline Cell Death But Increases Parp Inhibitor-Induced Germline Cell Death, Jorge Canar, Prima Manandhar-Sasaki, Jill Bargonetti

Publications and Research

The TP53 gene is mutated in over 50% of human cancers, and the C. elegans p53-1 (cep-1) gene encodes the ortholog CEP-1. CEP-1 is activated by ultraviolet type C (UVC)-induced DNA damage and activates genes that induce germline apoptosis. UVC treatment of gain-of-function glp-1(ar202gf)/Notch tumorous animals reduces germline stem cell numbers (and overall tumor size), while UVC treatment of double-mutant cep-1/p53(gk138);glp-1/Notch(ar202gf) increases DNA damage adducts and stem cell tumor volume. We compared UVC-induced mitotic stem cell death and animal lifespans for the two different C. elegans tumorous strains. C. elegans stem cell compartment death has never been observed, and we …

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Isolation And Characterization Of Fluorescent Proteins And Small Molecules From Marine Vertebrates, Sara Rose Krivoshik Sep 2022

Isolation And Characterization Of Fluorescent Proteins And Small Molecules From Marine Vertebrates, Sara Rose Krivoshik

Dissertations, Theses, and Capstone Projects

Fluorescence is a phenomenon in which a wavelength of light excites a fluorophore and then emits light at a higher, longer wavelength. This occurs throughout the biological world, in both the terrestrial and marine realms. Encompassing a diverse set of mechanisms from small molecules to large protein complexes; fluorescence has been used as a biological tool with a wide range of applications to study molecular and cellular biology for decades. This dissertation looks to identify and characterize novel fluorescent proteins and small molecules to allow for more efficient translation in developing new biotechnologies. Using a combination of RNA-Seq, Mass-Spec, protein …

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Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor Sep 2022

Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor

Dissertations, Theses, and Capstone Projects

The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target …

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Gamma Protocadherin Synaptic Localization And Intracellular Trafficking Is Consistent With Distinct Adhesive And Anti-Adhesive Roles In Development, Nicole Lamassa Sep 2022

Gamma Protocadherin Synaptic Localization And Intracellular Trafficking Is Consistent With Distinct Adhesive And Anti-Adhesive Roles In Development, Nicole Lamassa

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) constitute a family of cell adhesion molecules with approximately 60 Pcdh genes clustered in a 1 MB locus on chromosome 5q31 in humans. The Pcdh gene cluster is subdivided into α, β, and γ subclusters which encode related proteins. Individual neurons activate different subsets of Pcdh-α, Pcdh-β and Pcdh-γ genes by epigenetic mechanisms to generate distinct Pcdh adhesive units expressed by each neuron. This is thought to serve as a “surface barcode” for single-cell identity and synaptic recognition in the nervous system. The actual role for Pcdhs in neural development is still relatively unknown and different roles …

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Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik Sep 2022

Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) are a family of 60 adhesion-like molecules forming a neural barcode. In vertebrate neurons, 60 Pcdhs are coded by a large gene cluster. Numerous axons in the cluster are coding for the different extracellular, transmembrane, variable portion of the cytoplasmic and constant cytoplasmic domains where their expression is controlled epigenetically. These proteins mediate interactions between axons, dendrites, and glial cells during neural development. Yet, Pcdhs are not strictly adhesion molecules. In the amacrine cells of the retina, Pcdhs promote avoidance of the same cell dendrites, where in the cortex Pcdhs promote interactions between dendrites and astrocytes. In …

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Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible Sep 2022

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm-/- mice …

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Nup211 Plays An Important Role In Regulating Mrna Export And Stress Response, Ayana Ikenouchi Aug 2022

Nup211 Plays An Important Role In Regulating Mrna Export And Stress Response, Ayana Ikenouchi

Theses and Dissertations

Nup211 is a nuclear pore basket component in Schizosaccharomyces pombe and roles in the gating functions of NPCs. Using RT-qPCR, I found that in nup211-shutoff cells, the transcript levels of genes in mRNA export and stress-response pathways were significantly changed, suggesting nup211 is involved in regulating stress response pathways.

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The Molecular Mechanism Of Load Adaptation By Branched Actin Networks, Tai-De Li, Peter Bieling, Julian Weichsel, R Dyche Mullins, Daniel A. Fletcher Jun 2022

The Molecular Mechanism Of Load Adaptation By Branched Actin Networks, Tai-De Li, Peter Bieling, Julian Weichsel, R Dyche Mullins, Daniel A. Fletcher

Advanced Science Research Center

Branched actin networks are self-assembling molecular motors that move biological membranes and drive many important cellular processes, including phagocytosis, endocytosis, and pseudopod protrusion. When confronted with opposing forces, the growth rate of these networks slows and their density increases, but the stoichiometry of key components does not change. The molecular mechanisms governing this force response are not well understood, so we used single-molecule imaging and AFM cantilever deflection to measure how applied forces affect each step in branched actin network assembly. Although load forces are observed to increase the density of growing filaments, we find that they actually decrease the …

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Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip Jun 2022

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 …

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The Central Dogma: Gene Expression, Ayisha Sookdeo Apr 2022

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.

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A Novel Non‑Selective Atypical Pkc Agonist Could Protect Neuronal Cell Line From A Β ‑Oligomer Induced Toxicity By Suppressing A Β Generation, Dongmei Zou, Qian Li, Wenyang Pan, Peng Chen, Miao Sun, Xiaofeng Bao Feb 2022

A Novel Non‑Selective Atypical Pkc Agonist Could Protect Neuronal Cell Line From A Β ‑Oligomer Induced Toxicity By Suppressing A Β Generation, Dongmei Zou, Qian Li, Wenyang Pan, Peng Chen, Miao Sun, Xiaofeng Bao

Publications and Research

Atypical protein kinase C (aPKCs) serve key functions in embryonic development by regulating apical-basal polarity. Previous studies have shed light on their roles during adulthood, especially in the development of Alzheimer's disease (AD). Although the crystal structure of PKCι has been resolved, an agonist of aPKCs remains to be discovered. In the present study, by using the Discovery Studio program and LibDock methodology, a small molecule library (K66-X4436 KINA Set) of compounds were screened for potential binding to PKCι. Subsequently, the computational docking results were validated using affinity selection-mass spectrometry, before in vitro kinase activity was used to determine the …

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Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer Jan 2022

Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer

Advanced Science Research Center

Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane. Here we investigated the complex coacervation of anionic proteins with a block copolymer of opposite charge to form polyelectrolyte complex (PEC) micelles for use as a protein delivery vehicle. Using genetically modified variants of the model protein green fluorescent protein (GFP), …

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Oligomerization Of Mutant P53 R273h Is Not Required For Gain-Of-Function Chromatin Associated Activities, George K. Annor, Nour Elshabassy, Devon Lundine, Don-Gerard Conde, Gu Xiao, Viola Ellison, Jill Bargonetti Nov 2021

Oligomerization Of Mutant P53 R273h Is Not Required For Gain-Of-Function Chromatin Associated Activities, George K. Annor, Nour Elshabassy, Devon Lundine, Don-Gerard Conde, Gu Xiao, Viola Ellison, Jill Bargonetti

Publications and Research

The TP53 gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the C-terminal oligomerization domain (OD). These types of mutations are found in patients with the rare inherited cancer predisposition disorder called Li-Fraumeni syndrome. We previously found that mutant p53 (mtp53) R273H associates with replicating DNA and promotes the chromatin association of replication-associated proteins mini-chromosome maintenance 2 (MCM2), and poly ADP-ribose polymerase 1(PARP1). Herein, we created dual mutants in order to test if the oligomerization state of mtp53 R273H played a role in chromatin binding oncogenic gain-of-function (GOF) activities. …

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Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo Oct 2021

Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo

Publications and Research

Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …

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Regulatory Non-Coding Rnas Modulate Transcriptional Activation During B Cell Development, Mary Attaway, Tzippora Chwat-Edelstein, Bao Q. Vuong Oct 2021

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 …

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Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin Sep 2021

Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin

Publications and Research

Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was …

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Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine Sep 2021

Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine

Dissertations, Theses, and Capstone Projects

Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the chromatin localization of several DNA replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the castration-resistant prostate cancer cell line DU145, we examine two mutant p53 …

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The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber Sep 2021

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

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Analysis Of Transplantable Photoreceptor Replacement Cell Chemotactic Mechanisms In Retinal Biomimetic Ligand Gradients, Onyekwere Onwumere Sep 2021

Analysis Of Transplantable Photoreceptor Replacement Cell Chemotactic Mechanisms In Retinal Biomimetic Ligand Gradients, Onyekwere Onwumere

Dissertations, Theses, and Capstone Projects

Disease or trauma induced loss of rod and cone photoreceptors is a major cause of vision loss worldwide. To replace lost photoreceptors and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal injection of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). A major obstacle in the field is that transplanted photoreceptor replacement cells exhibit extremely limited migration into host retina following injection into the subretinal space. In this work, we show that PPCs and host retinal interaction bioinformatics modeling can identify key pathways involved in photoreceptor replacement cell migration and invasion behaviors. In addition, …

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