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University of Massachusetts Medical School

Cellular and Molecular Physiology

Cell Death

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Full-Text Articles in Life Sciences

Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma Oct 2019

Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma

Open Access Articles

BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- kappaB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice.

METHODS: Human IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKbeta in IEC (Ikkbeta(EE)(IEC)), Ripk1(D138N/D138N) knockin mice, and Ripk3(-/-) mice were injected with TNF or lipopolysaccharide. Enteroids were ...


Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko Sep 2015

Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade.

FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than ...


Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski May 2015

Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski

GSBS Dissertations and Theses

Sterile particles underlie the pathogenesis of numerous inflammatory diseases. These diseases can often become chronic and debilitating. Moreover, they are common, and include silicosis (silica), asbestosis (asbestos), gout (monosodium urate), atherosclerosis (cholesterol crystals), and Alzeihmer’s disease (amyloid Aβ). Central to the pathology of these diseases is a repeating cycle of particle-induced cell death and inflammation. Macrophages are the key cellular mediators thought to drive this process, as they are especially sensitive to particle-induced cell death and they are also the dominant producers of the cytokine responsible for much of this inflammation, IL-1β. In response to cytokines or microbial cues ...


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 ...


Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu Feb 2015

Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu

GSBS Dissertations and Theses

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration. Two causative genes have been identified so far, WFS1 and WFS2, both encoding endoplasmic reticulum (ER) localized transmembrane proteins. Since WFS1 is involved in the ER stress pathway, Wolfram syndrome is considered an ER disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome, the molecular mechanism linking ER to the death of β cells and neurons has not been elucidated.

The endoplasmic reticulum (ER) is an organelle that forms a network of enclosed sacs and tubes that connect the nuclear membrane and other organelles including Golgi and ...