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

Cell Biology Commons

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

Articles 1 - 4 of 4

Full-Text Articles in Cell Biology

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 ...


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 ...


Defective Autophagy In Neurodegeneration: Novel Roles For Huntingtin And Optineurin In Regulating Autophagosome Dynamics, Chyi Haw Yvette Wong Jan 2015

Defective Autophagy In Neurodegeneration: Novel Roles For Huntingtin And Optineurin In Regulating Autophagosome Dynamics, Chyi Haw Yvette Wong

Publicly Accessible Penn Dissertations

Autophagy is an essential cellular degradative process that has been implicated in the pathogenesis of several neurodegenerative diseases including Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). During autophagy, autophagosomes form around cargo such as mitochondria, and subsequently fuse with lysosomes to acidify and acquire enzymes to degrade internalized cargos. In neurons, constitutive autophagosome biogenesis preferentially occurs at the axon tip, followed by the robust retrograde axonal transport of autophagosomes back to the cell body. The mechanisms regulating both the axonal transport of autophagosomes and the selective degradation of damaged mitochondria have not yet been determined. Here, I report novel ...


The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik Jan 2013

The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik

Publicly Accessible Penn Dissertations

Cytoplasmic alpha-synuclein (a-syn) aggregates, including Lewy bodies (LBs), are pathological hallmarks of a number of neurodegenerative diseases, most notably Parkinson's disease (PD). Activation of intracellular protein degradation pathways (Pdps) to eliminate these aggregates has been proposed as a therapeutic approach for PD and other synucleinopathies, but the interplay between LB-like a-syn aggregates and Pdps is not completely understood. Here, we investigate this interplay by utilizing a recently developed cellular model in which intracellular LB-like a-syn inclusions accumulate after delivery of pre-formed a-syn fibrils (Pffs) into a-syn-expressing HEK293 cells or cultured primary neurons. This thesis describes the interplay between LB-like ...