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Articles 1051 - 1080 of 7399
Full-Text Articles in Cell and Developmental Biology
Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim
Graduate Theses, Dissertations, and Problem Reports (ETD)
Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …
Immunomodulation In Osteosarcoma: From Therapy To Diagnostics, Ryan Austin Lacinski
Immunomodulation In Osteosarcoma: From Therapy To Diagnostics, Ryan Austin Lacinski
Graduate Theses, Dissertations, and Problem Reports (ETD)
Osteosarcoma (OS) is a rare pediatric bone malignancy. Those who develop advanced disease, often in the form of metastasis to the lung, experience poor five-year survival rates near approximately 25%. Considering minimal-to-no therapeutic breakthroughs have occurred for treatment of this disease since the 1980s, efforts to develop new therapeutics are underway. The goal of this dissertation was to initiate the preclinical efforts necessary to reinvigorate the use of immunostimulatory cytokine therapy for the treatment of OS and other solid tumors. This effort would not only include the development of the immunotherapeutic known as IL12ns, but also the clinical diagnostic tools …
Identification And Therapeutic Targeting Of Metabolic Alterations In Estrogen Receptor-Positive Breast Cancer, Steven Tau
Dartmouth College Ph.D Dissertations
Estrogen receptor-positive breast cancer remains one of the most frequently diagnosed cancers in women. Despite adjuvant endocrine therapy reducing the rate of recurrence, there remains a significant proportion of patients whose breast cancer will recur years to decades after the initial diagnosis. The underlying biology of tumor cells in the period between initiation of adjuvant therapy and recurrence is relatively unexplored, preventing the development of better treatment options. From a genome-wide screening approach, we identified and characterized broad metabolic reprogramming associated with the persistent cell state. We demonstrate that a decreased ability to metabolize glucose in turn pushes a higher …
Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng
Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng
Dartmouth College Ph.D Dissertations
Accurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.
Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To …
Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang
Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang
Dartmouth College Ph.D Dissertations
The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …
Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin
Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin
Dissertations, Master's Theses and Master's Reports
Synthetic long oligodeoxynucleotides (ODNs) have found wide applications in diverse fields such as chemical biology, synthetic biology, and genes and genomes synthesis. Those applications leading to a significant demand for their production. However, traditional methods for purifying synthetic ODNs present notable drawbacks, particularly their inability to purify long ODNs, rendering long ODN synthesis challenging. To address these issues, chemical synthesis techniques for long ODNs coupled with non-chromatographic purification methods have been developed. This technology makes the purification of long synthetic ODNs feasible and offers a viable pathway for producing genes and genomes with extensive repeats or stable secondary structures, which …
Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens
Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens
Undergraduate Research Posters
Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.
To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …
A Comparison Of Three Dna Extraction Methods On 45-Year-Old Pupae Cases, Ananya Udyaver, Casey Flint, Jeffery Tomberlin, Baneshwar Singh
A Comparison Of Three Dna Extraction Methods On 45-Year-Old Pupae Cases, Ananya Udyaver, Casey Flint, Jeffery Tomberlin, Baneshwar Singh
Undergraduate Research Posters
Blow flies are the primary colonizers of human cadavers. In many death investigations, insect evidence can help in prediction of minimum post-mortem interval (PMImin) but to do that, the first step is to identify collected insect evidence. For immature stages, morphological keys are either limited or incomplete and hence DNA based identification is used. For DNA based ID, DNA extraction is the first and the most important step, especially when collected evidence is highly degraded. The main aim of this study was to compare three DNA extraction methods (QIAgen Blood and Tissue Kit, organic, and QIAgen DNA Investigator Kit) to …
Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil
Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil
Biology Faculty Publications
In this paper, we examined the degree to which inherent spatial structure in soil properties influences the outcomes of machine learning (ML) approaches to predicting soil spatial variability. We compared the performances of four ML algorithms (support vector machine, artificial neural network, random forest, and random forest for spatial data) against two non-ML algorithms (ordinary least squares regression and spatial filtering regression). None of the ML algorithms produced residuals that had lower mean values or were less autocorrelated over space compared with the non-ML approaches. We recommend the use of random forest when a soil variable of interest is weakly …
Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder
Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological …
27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland
27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.
METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …
Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka
Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE2/EP2 feedforward loop, …
Melittin: A Natural Component Of Honeybee Venom As A Potential Anti-Cancer Therapy, Niamh Donnellan, Anne M. Friel
Melittin: A Natural Component Of Honeybee Venom As A Potential Anti-Cancer Therapy, Niamh Donnellan, Anne M. Friel
SURE Journal: Science Undergraduate Research Experience Journal
Cancer is a major cause of death worldwide and while chemotherapy is the main approach there are many negative associations in current treatment procedures. These include lack of selectivity, side effects and drug resistance. The hallmarks of cancer are a fundamental concept which aids the development of new means to treat human cancers through the understanding of the acquisition of these hallmarks from cells.
Melittin is a major peptide component of bee venom which has shown to be efficacious as an anticancer agent in preclinical and animal models. Melittin has many biological functions including pore formation in the phospholipid bilayer …
Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu
Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …
Regulation Of Mrna And Circrna As A Cause And Consequence Of Aging In Caenorhabditis Elegans, Rebekah Napier-Jameson
Regulation Of Mrna And Circrna As A Cause And Consequence Of Aging In Caenorhabditis Elegans, Rebekah Napier-Jameson
Biological Sciences Theses and Dissertations
A role for RNA binding proteins in regulating lifespan has emerged. We identified a pair of neuronal RBPs, exc-7 and mbl-1, which display synthetic lifespan defects. Such a strong synthetic phenotype represented an opportunity to use transcriptomics to search for potential causative targets that are synthetically regulated. We identified a small handful of genes synthetically dysregulated in double mutants and systematically tested each candidate gene for functional contribution to the exc-7; mbl-1 lifespan phenotype. We identified one such gene, the ion transporter nhx-6, which is highly upregulated in double mutants. Overexpression of nhx-6 causes reduced lifespan, and deletion …
Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump
Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump
Electronic Theses and Dissertations
Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …
Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty
Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty
Theses & Dissertations
Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.
Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …
Role Of The Ganglioside Gd2 And Its Biosynthetic Enzyme Gd3 Synthase In Prostate Cancer Tumorigenesis, Aaqib Bhat
Role Of The Ganglioside Gd2 And Its Biosynthetic Enzyme Gd3 Synthase In Prostate Cancer Tumorigenesis, Aaqib Bhat
Theses & Dissertations
Despite significant advancements in managing localized prostate cancer (PC), which have notably increased survival rates, advanced PC continues to be a leading cause of cancer- related fatalities. The discovery of new pathways that can be targeted to inhibit tumor growth in PC could pave the way for innovative treatment strategies. The disialylganglioside GD2 is an FDA-approved target for antibody therapies in neuroblastoma and has not been extensively studied in the context of PC. The work done in this thesis reveals that GD2 is present on a minor subset of PC cells in certain patients and is more prevalent in metastatic …
Synergetic Signaling Between The Chlamydia Secreted Effectors Tarp And Tmea Regulates Actin Kinetics And Efficient Entry, Matthew Romero
Synergetic Signaling Between The Chlamydia Secreted Effectors Tarp And Tmea Regulates Actin Kinetics And Efficient Entry, Matthew Romero
Theses & Dissertations
Chlamydia trachomatis is both the leading cause of non-congenital preventable blindness in developing nations and the leading source of bacterial sexually transmitted infections. As an obligate intracellular pathogen, Chlamydia has an absolute requirement on gaining entry into its host, which is accomplished by manipulating the host actin cytoskeleton to assemble engulfment structures that drive pathogen entry. In support of this, Chlamydia secretes the effectors TarP and TmeA via a type-III secretion system, whose respective signaling outputs operate synergistically to generate rapid actin kinetics and efficient pathogen engulfment. Rapid actin recruitment characteristic of invading Chlamydia is derived from a collaborative interaction …
Role Of Gonadotropin-Releasing Hormone 2 And Its Receptor In Human Reproductive Cancers, Dr. Amy T. Desaulniers, Brett White
Role Of Gonadotropin-Releasing Hormone 2 And Its Receptor In Human Reproductive Cancers, Dr. Amy T. Desaulniers, Brett White
School of Veterinary and Biomedical Sciences: Faculty Publications
Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues …
Deep Learning Image Analysis To Isolate And Characterize Different Stages Of S-Phase In Human Cells, Kevin A. Boyd, Rudranil Mitra, John Santerre, Christopher L. Sansam
Deep Learning Image Analysis To Isolate And Characterize Different Stages Of S-Phase In Human Cells, Kevin A. Boyd, Rudranil Mitra, John Santerre, Christopher L. Sansam
SMU Data Science Review
Abstract. This research used deep learning for image analysis by isolating and characterizing distinct DNA replication patterns in human cells. By leveraging high-resolution microscopy images of multiple cells stained with 5-Ethynyl-2′-deoxyuridine (EdU), a replication marker, this analysis utilized Convolutional Neural Networks (CNNs) to perform image segmentation and to provide robust and reliable classification results. First multiple cells in a field of focus were identified using a pretrained CNN called Cellpose. After identifying the location of each cell in the image a python script was created to crop out each cell into individual .tif files. After careful annotation, a CNN was …
Pathogenicity Of Acinetobacter Calcoaceticus, Kaitlan A. Sullivan
Pathogenicity Of Acinetobacter Calcoaceticus, Kaitlan A. Sullivan
MUSC Theses and Dissertations
Acinetobacter is a genus of gram-negative bacteria that have been appearing frequently in hospitals contributing to infections in the blood, lungs, urinary tract, and other parts of the body. It infects patients with weakened immune systems that are placed on ventilators, after the use of catheters, or have any other open wounds produced by prolonged hospital stays. This genus of bacteria is problematic due to its high probability of becoming resistant to multiple classes of antibiotics. Thus, we are determining the pathogenicity of clinical isolates of Acinetobacter calcoaceticus using the organism Caenorhabditis elegans as a model.
We are testing …
Pediatric Parosteal Osteosarcoma Of The Distal Radius Causing Extensive Erosive Mass Effect Of The Adjacent Ulna: A Case Report, Andrea Perloff, Sehoon Park, Robert Panganiban, John Devries
Pediatric Parosteal Osteosarcoma Of The Distal Radius Causing Extensive Erosive Mass Effect Of The Adjacent Ulna: A Case Report, Andrea Perloff, Sehoon Park, Robert Panganiban, John Devries
Department of Orthopaedics Faculty Research
Introduction: Parosteal osteosarcomas are low-grade bony malignancies that are treated primarily with surgical resection and reconstruction. This report discusses a unique case of a pediatric patient who presented with a parosteal osteosarcoma of the distal radius causing extensive erosive mass effect and growth disturbance of the adjacent ulna. Likely due to their slow-growing nonaggressive nature, parosteal osteosarcomas have not been previously described to abut adjacent bony structures through direct contact. The patient presented in a significantly delayed manner due to social circumstances, inadvertently revealing this novel behavior. This report reviews this rare case and describes the current understanding of this …
Mitochondrial Gtp Metabolism Controls Reproductive Aging In C. Elegans, Yi-Tang Lee, Marzia Savini, Tao Chen, Yang, Jin, Qian Zhao, Lang Ding, Shihong Max Gao, Jessica N. Sowa, Jue D. Wang, Meng C. Wang
Mitochondrial Gtp Metabolism Controls Reproductive Aging In C. Elegans, Yi-Tang Lee, Marzia Savini, Tao Chen, Yang, Jin, Qian Zhao, Lang Ding, Shihong Max Gao, Jessica N. Sowa, Jue D. Wang, Meng C. Wang
Biology Faculty Publications
Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP (mtGTP) metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP-but not ATP-specific succinyl-CoA synthetase (SCS) promotes reproductive longevity in Caenorhabditis elegans. We further identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion …
Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto
Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto
Kimmel Cancer Center Faculty Papers
Raf-1, a multifunctional kinase, regulates various cellular processes, including cell proliferation, apoptosis, and migration, by phosphorylating MAPK/ERK kinase and interacting with specific kinases. Cellular Raf-1 activity is intricately regulated through pathways involving the binding of regulatory proteins, direct phosphorylation, and the ubiquitin-proteasome axis. In this study, we demonstrate that PHI-1, an endogenous inhibitor of protein phosphatase-1 (PP1), plays a pivotal role in modulating Raf-1 proteostasis within cells. Knocking down endogenous PHI-1 in HEK293 cells using siRNA resulted in increased cell proliferation and reduced apoptosis. This heightened cell proliferation was accompanied by a 15-fold increase in ERK1/2 phosphorylation. Importantly, the observed …
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman
Chemistry & Biochemistry Undergraduate Honors Theses
The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.3 To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …
Cell Aggregation Activates Small Gtpase Rac1 And Induces Cd44 Cleavage By Maintaining Lipid Raft Integrity, Dong Li, Younhee Park, Hami Hemati, Xia Liu
Cell Aggregation Activates Small Gtpase Rac1 And Induces Cd44 Cleavage By Maintaining Lipid Raft Integrity, Dong Li, Younhee Park, Hami Hemati, Xia Liu
Markey Cancer Center Faculty Publications
Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell detachment from the extracellular matrix (ECM) triggers lipid raft disruption and anoikis, which is a barrier for cancer cells to metastasize. Compared to single circulating tumor cells (CTCs), our recent studies have demonstrated that CD44-mediatd cell aggregation enhances the stemness, survival and metastatic ability of aggregated cells. Here, we investigated whether and how lipid rafts are involved in CD44-mediated cell aggregation. We found that cell detachment, which mimics the condition when tumor cells detach from the ECM …
Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley
Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley
Saha Cardiovascular Research Center Faculty Publications
Background and aims: Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role of liver-specific CPT1a on hepatic lipid metabolism.
Approach and results: Male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (60% kcal fat) for 15 weeks. Mice were necropsied after a 16 h fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging, kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine …
Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil
Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil
Electronic Theses and Dissertations
Understanding how innocuous organisms can evolve to be pathogenic to humans is of increasing global concern. Further, understanding how existing pathogens may evolved to be more virulent is also vital to our ability to provide healthcare to people afflicted with diseases that promote chronic bacterial infections, such as cystic fibrosis. With the rise of antibiotic resistance in both bacteria and fungi it is paramount that new therapeutics are identified. Understanding what mutations occur that result in increased virulence in microbes can potentially provide new targets for antimicrobial drugs to combat antibiotic resistance. The Coincidental Evolution Hypothesis is a fundamental hypothesis …
Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi
Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi
Graduate Theses and Dissertations
Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …