Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

PDF

Autophagy

Discipline
Institution
Publication Year
Publication
Publication Type

Articles 1 - 30 of 44

Full-Text Articles in Cell Biology

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks Jan 2019

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine ...


Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham Dec 2018

Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Autophagy is a major degradation and recycling pathway in plants. It functions to maintain cellular homeostasis and is induced by environmental cues and developmental stimuli. Over the past decade, the study of autophagy has expanded from model plants to crop species. Many features of the core machinery and physiological functions of autophagy are conserved among diverse organisms. However, several novel functions and regulators of autophagy have been characterized in individual plant species. In light of its critical role in development and stress responses, a better understanding of autophagy in crop plants may eventually lead to beneficial agricultural applications. Here, we ...


The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman Nov 2018

The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman

Open Access Articles

Macroautophagy and cell death both contribute to innate immunity, but little is known about how these processes integrate. Drosophila larval salivary glands require autophagy for developmentally programmed cell death, and innate immune signaling factors increase in these dying cells. Here, we show that the nuclear factor kappaB (NF-kappaB) factor Relish, a component of the immune deficiency (Imd) pathway, is required for salivary gland degradation. Surprisingly, of the classic Imd pathway components, only Relish and the PGRP receptors were involved in salivary gland degradation. Significantly, Relish controls salivary gland degradation by regulating autophagy but not caspases. In addition, expression of either ...


Ire1b Degrades Rnas Encoding Proteins That Interfere With The Induction Of Autophagy By Er Stress In Arabidopsis Thaliana, Yan Bao, Yunting Pu, Xiang Yu, Brian D. Gregory, Renu Srivastava, Stephen H. Howell, Diane C. Bassham Aug 2018

Ire1b Degrades Rnas Encoding Proteins That Interfere With The Induction Of Autophagy By Er Stress In Arabidopsis Thaliana, Yan Bao, Yunting Pu, Xiang Yu, Brian D. Gregory, Renu Srivastava, Stephen H. Howell, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Macroautophagy/autophagy is a conserved process in eukaryotes that contributes to cell survival in response to stress. Previously, we found that endoplasmic reticulum (ER) stress induces autophagy in plants via a pathway dependent upon AT5G24360/IRE1B (INOSITOL REQUIRING 1–1), an ER membrane-anchored factor involved in the splicing of AT1G42990/BZIP60 (basic leucine zipper protein 60) mRNA. IRE1B is a dual protein kinase and ribonuclease, and here we determined the involvement of the protein kinase catalytic domain, nucleotide binding and RNase domains of IRE1B in activating autophagy. We found that the nucleotide binding and RNase activity of IRE1B, but not ...


Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu Jan 2018

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu

GSBS Dissertations and Theses

Proper functioning of endocrine cells is crucial for organismal homeostasis. The underlying mechanisms that fine-tune the amount, and the timing of hormone secretion are not clear. JIP1 / MAPK8IP1 (JNK interacting protein 1) is a scaffold protein that mediates cellular stress response, and is highly expressed in endocrine cells, including insulin secreting b-cells in pancreas islets. However, the role of JIP1 in b-cells is unclear. This study demonstrates that b-cell specific Jip1 ablation results in decreased glucose-induced insulin secretion, without a change in Insulin1 and Insulin2 gene expression. Inhibition of both JIP1-kinesin interaction, and JIP1-JNK interaction by genetic mutations also resulted ...


Investigating Autophagy, Extracellular Vesicles, And Glycobiology, Benjamin Cook Jan 2018

Investigating Autophagy, Extracellular Vesicles, And Glycobiology, Benjamin Cook

Master's Theses

Autophagy is a cellular process of degradation which degrades cellular materials in acidic organelles called lysosomes. Impairment of lysosomal degradation can lead to lysosomal storage disorders such as Parkinson's Disease. In Parkinson's Disease neurotoxic α-synuclein can spread from cell-to-cell via extracellular vesicles. We investigated the changes in extra vesicular glycans upon perturbation of autophagy using a class of glycan binding molecules termed lectins.

We found that upon induction of autophagy causes EV glycans to increase while others remained consistent. Additionally, we found that specific glycans are increased more than others. Conversely, when lysosomal degradation was impaired, we ...


Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley N. Munie Nov 2017

Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley N. Munie

Steeplechase: An ORCA Student Journal

Autophagy, the cell's recycling system, is a highly-conserved survival mechanism of the cell. Autophagy has been implicated in the mediation of the removal of cytotoxic aggregates, such as those linked to neurodegenerative disorders like Huntington and Alzheimer disease. Studies in several model organisms have identified numerous genes involved in mediating autophagy, including the Puromycin sensitive aminopeptidase (Psa). The Caenorhabditis elegans orthologue of Psa, pam-1, also governs fertility. Along with apoptosis, a form of regulated cell death, autophagy has been found to be required for efficient C. elegans oogenesis. When autophagy is suppressed through RNAi in worms harboring a pam-1 ...


Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder Aug 2017

Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder

UT GSBS Dissertations and Theses (Open Access)

MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine ...


Tor-Dependent And -Independent Pathways Regulate Autophagy In Arabidopsis Thaliana, Yunting Pu, Xinjuan Luo, Diane C. Bassham Jul 2017

Tor-Dependent And -Independent Pathways Regulate Autophagy In Arabidopsis Thaliana, Yunting Pu, Xinjuan Luo, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Autophagy is a critical process for recycling of cytoplasmic materials during environmental stress, senescence and cellular remodeling. It is upregulated under a wide range of abiotic stress conditions and is important for stress tolerance. Autophagy is repressed by the protein kinase target of rapamycin (TOR), which is activated in response to nutrients and in turn upregulates cell growth and translation and inhibits autophagy. Down-regulation of TOR in Arabidopsis thaliana leads to constitutive autophagy and to decreased growth, but the relationship to stress conditions is unclear. Here, we assess the extent to which TOR controls autophagy activation by abiotic stress. Overexpression ...


Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin Jun 2017

Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin

GSBS Dissertations and Theses

Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a ...


The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano Jun 2017

The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano

All Dissertations, Theses, and Capstone Projects

Autophagy and endocytosis are two cellular pathways that are vital to cell growth and homeostasis. Autophagy is a dynamic and catabolic process involving the formation of a double-membrane vesicle called the autophagosome, which engulfs long-lived proteins and damaged organelles. Endocytosis involves the uptake of extracellular material into the cell through the formation of intracellular vesicles termed endosomes. Although both endocytosis and autophagy are interconnected processes, the extent to which endocytic proteins and/or compartments contribute to autophagy, and how these endocytic components do so, is still unknown. To improve our understanding of the connections that exist between autophagy and endocytosis ...


The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher May 2017

The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher

Electronic Theses and Dissertations

Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line ...


Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley Munie May 2017

Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley Munie

Honors College Theses

Autophagy, the cell's recycling system, is a highly-conserved survival mechanism of the cell. Autophagy has been implicated in the mediation of the removal of cytotoxic aggregates, such as those linked to neurodegenerative disorders like Huntington and Alzheimer disease. Studies in several model organisms have identified numerous genes involved in mediating autophagy, including the Puromycin sensitive aminopeptidase (Psa). The Caenorhabditis elegans orthologue of Psa, pam-1, also governs fertility. Along with apoptosis, a form of regulated cell death, autophagy has been found to be required for efficient C. elegans oogenesis. When autophagy is suppressed through RNAi in worms harboring a pam-1 ...


The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton May 2017

The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton

UT GSBS Dissertations and Theses (Open Access)

DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the ...


Hlh-30/Tfeb-Mediated Autophagy Functions In A Cell-Autonomous Manner For Epithelium Intrinsic Cellular Defense Against Bacterial Pore-Forming Toxin In C. Elegans, Huan-Da Chen, Raffi V. Aroian, Chang-Shi Chen Feb 2017

Hlh-30/Tfeb-Mediated Autophagy Functions In A Cell-Autonomous Manner For Epithelium Intrinsic Cellular Defense Against Bacterial Pore-Forming Toxin In C. Elegans, Huan-Da Chen, Raffi V. Aroian, Chang-Shi Chen

Open Access Articles

Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways ...


Characterizing A Signaling Network That Maintains Hematopoietic Stem Cells, Michelle Nguyen-Mccarty Jan 2017

Characterizing A Signaling Network That Maintains Hematopoietic Stem Cells, Michelle Nguyen-Mccarty

Publicly Accessible Penn Dissertations

Hematopoietic stem cells (HSCs) are able to self-renew and to differentiate into all blood cells. HSCs reside in a low-perfusion niche and depend on local signals to survive and to maintain the capacity for self-renewal. HSCs removed from the niche can survive if they receive hematopoietic cytokines, but they then lose the ability to self-renew. However, we showed previously that simultaneous inhibition of glycogen synthase kinase-3 (GSK-3) and mammalian target of rapamycin complex 1 (mTORC1) maintains HSC function ex vivo without the need for exogenous cytokines. As these experiments were initially done in heterogeneous cell populations, I then showed that ...


Two Components Of Maintaining Developmental Competence: Microrna-21 In The Maturing Oocyte And Autophagy Induction In The Follicular Stage Ovary, Benjamin J. Hale Jan 2017

Two Components Of Maintaining Developmental Competence: Microrna-21 In The Maturing Oocyte And Autophagy Induction In The Follicular Stage Ovary, Benjamin J. Hale

Graduate Theses and Dissertations

This dissertation describes two processes that the oocyte and ovary potentially utilize to maintain reproductive competence: autophagy in response to heat stress and microRNA-21 function during meiotic maturation. Heat stress (HS) occurs when heat accumulation (from internal and external sources) exceeds heat dissipation. HS is associated with seasonal infertility and therefore is a production issue and profitability constraint in the swine industry. Autophagy is the process by which somatic cells recycle cellular components and it is activated by a variety of stressors. Therefore, characterizing autophagy in the ovary and oocyte is valuable because of the potential of autophagy to mitigate ...


Interaction Between Regulation Of Autophagy, Stress Responses And Growth In Arabidopsis Thaliana, Yunting Pu Jan 2017

Interaction Between Regulation Of Autophagy, Stress Responses And Growth In Arabidopsis Thaliana, Yunting Pu

Graduate Theses and Dissertations

Plants have evolved sophisticated mechanisms to balance between growth and stress tolerance upon changing environmental conditions. Autophagy is a critical process for recycling of cytoplasmic materials during nutrient remodeling and stress responses. Upon activation, the materials to be degraded are engulfed by a double-membrane vesicle called an autophagosome, which delivers the cargo to the vacuole for degradation and recycling. Studies in plants have revealed genes that are involved in the core machinery of autophagosome formation and delivery, and key regulators of autophagy. However, the upstream regulators of autophagy and the functions of autophagy in balancing growth and stress tolerance remain ...


Autophagy Activation By Transcription Factor Eb (Tfeb) In Striatum Of Hdq175/Q7 Mice, Petr Vodicka, Kathryn O. Chase, Maria Iuliano, Adelaide Tousley, Dana T. Valentine, Ellen Sapp, Kimberly B. Kegel-Gleason, Miguel Sena-Esteves, Neil Aronin, Marian Difiglia Oct 2016

Autophagy Activation By Transcription Factor Eb (Tfeb) In Striatum Of Hdq175/Q7 Mice, Petr Vodicka, Kathryn O. Chase, Maria Iuliano, Adelaide Tousley, Dana T. Valentine, Ellen Sapp, Kimberly B. Kegel-Gleason, Miguel Sena-Esteves, Neil Aronin, Marian Difiglia

Open Access Articles

BACKGROUND: Mutant huntingtin (mHTT) is encoded by the Huntington's disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy.

OBJECTIVE: To examine if increasing TFEB protein levels in HD mouse striatum induces autophagy and influences mHTT levels.

METHODS: We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7 mice using adeno-associated virus AAV2/9. The levels ...


Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan Aug 2016

Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan

Molecular, Cell and Cancer Biology Publications

BACKGROUND: ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer.

RESULTS: Here, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech Mar 2016

Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion ...


Decorin As A Multivalent Therapeutic Agent Against Cancer., Thomas Neill, Liliana Schaefer, Renato V. Iozzo Feb 2016

Decorin As A Multivalent Therapeutic Agent Against Cancer., Thomas Neill, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target-rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition ...


Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan Jan 2016

Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan

Cell Biology, Microbiology, and Molecular Biology Faculty Publications

Background: miRNAs can regulate cellular survival in various cancer cell types. Recent evidence implicates the formation of lipid droplets as a hallmark event during apoptotic cell death response. It is presently unknown whether MIR494, located at 14q32 which is deleted in renal cancers, reduces cell survival in renal cancer cells and if this process is accompanied by changes in the number of lipid droplets.

Methods: 769-P renal carcinoma cells were utilized for this study. Control or MIR494 mimic was expressed in these cells following which cell viability (via crystal violet) and apoptotic cell numbers (via Annexin V/PI staining) were ...


Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola Dec 2015

Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola

Theses and Dissertations

Autophagy or cellular self-digestion, a lysosomal degradation pathway that is conserved from yeast to human, plays a key role in recycling cellular constituents, including damaged organelles. It also plays a pivotal role in the adaptation of cells to a plethora of distinct stressors including starvation. Autophagy has been extensively studied in mammals and yeast, but little is known in avian species. Thus, the major objective of the present study was to determine the effects of leptin on autophagy-related genes in chicken hypothalamus, muscle and liver. Leptin is an adipocytokine that is mostly produced by white adipose cells in mammals (as ...


Current Questions And Possible Controversies In Autophagy, L M. Lindqvist, A K. Simon, Eric H. Baehrecke Nov 2015

Current Questions And Possible Controversies In Autophagy, L M. Lindqvist, A K. Simon, Eric H. Baehrecke

Open Access Articles

Interest in autophagy has exploded over the last decade, with publications highlighting crosstalk with several other cellular processes including secretion, endocytosis, and cell suicide pathways including apoptosis. Autophagy proteins have also been implicated in other cellular processes independently of their roles in autophagy, creating complexities in the interpretation of autophagy (Atg) mutant gene data. Interestingly, this self-eating process is a survival mechanism that can also promote cell death, but when and how autophagy may 'switch' its function is still under debate. Indeed, there are currently many models of how autophagy actually influences cell death. In this review, we highlight some ...


Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy Apr 2015

Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy

GSBS Dissertations and Theses

Autophagy is a conserved catabolic process that traffics cellular components to the lysosome for degradation. Autophagy is required for cell survival during nutrient restriction, but it has also been implicated in programmed cell death. It is associated with several diseases, including cancer. Cancer is a disease characterized by aberrant cell growth and proliferation. To support this growth, the tumor cell often deregulates several metabolic processes, including autophagy. Interestingly, autophagy plays paradoxical roles in tumorigenesis. It has been shown to be both tumor suppressive through cell death mechanisms and tumor promoting through its cytoprotective properties. However, the mechanisms regulating the balance ...


Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson Mar 2015

Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson

GSBS Dissertations and Theses

Autophagy delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. Although the regulation and role that autophagy plays in stress, infection, and survival is apparent, its involvement during cell death remains relatively unclear. In this thesis I summarize what is known about the roles autophagy can play in cell death, and the differences between the utilization of autophagy during nutrient deprivation and cell death. Utilizing Drosophila melanogaster as a model system, the roles autophagy plays in both of these contexts can be studied. The goal of this ...


Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi Jan 2015

Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi

GSBS Dissertations and Theses

Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of autophagy. However, the role of autophagy itself in tumorigenesis is context-dependent and can be both preventive and promoting. Due to its dual function in cancer a better understanding of this process is necessary to develop potential novel cancer therapies. To gain insight into the role of autophagy in breast carcinoma, I analyzed the autophagydependency of different subtypes of breast cancer. My results implicate that triple-negative breast carcinoma ...


Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa Jan 2015

Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa

Publicly Accessible Penn Dissertations

Soft tissue sarcomas (STS) are a group of malignancies that arise from mesenchymal tissue, consisting of over 50 distinct histiologic subtypes. Unfortunately, the five-year survival rate of sarcoma patients has remained relatively unchanged, and due to the rarity of the disease, research and development of adequate therapeutics for STS lags behind other cancers. Therefore, understanding the molecular drivers of STS is important in developing new therapeutics, as well as discovering druggable processes that occur across multiple subtypes. One feature common to STS is hypoxia, or low O2 conditions. Using molecular biology, biochemical approaches, genetically engineered mouse models, as well as ...