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Full-Text Articles in Molecular 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 ...


Novel Roles For The Tumor Suppressor Apc Through Regulation Of Gsk-3, Alexander James Valvezan Jan 2013

Novel Roles For The Tumor Suppressor Apc Through Regulation Of Gsk-3, Alexander James Valvezan

Publicly Accessible Penn Dissertations

Adenomatous Polyposis Coli (APC) is a tumor suppressor and essential negative regulator of the Wnt signaling pathway. Wnt signaling is crucial for proper patterning and cell fate specification during development and regulates stem cell homeostasis throughout adulthood. Mutations in Apc are strongly linked to human colorectal cancers and these mutations aberrantly activate Wnt signaling. How APC regulates the Wnt pathway and how oncogenic Apc mutations activate Wnt signaling and promote tumorigenesis are not fully understood. To address these questions, we utilized in vitro reconstitution assays, as well as Apc knockdown or mutation in human cells, zebrafish, and mice. We find ...


Development And Regulation Of Natural T Helper 17 Cells, Ji-Yeon Kim Jan 2012

Development And Regulation Of Natural T Helper 17 Cells, Ji-Yeon Kim

Publicly Accessible Penn Dissertations

CD4+ T helper (Th) cells are essential components of the adaptive immune system that orchestrate the immune response by producing a distinct array of cytokines specific to each subset. Th17 cells, the IL-17 producing subset of the CD4+ Th cell family, are critical for host defense again extracellular pathogens, especially at barrier and mucosal sites. Dysregulation of Th17 cells, meanwhile, leads to the pathogenesis of a number of autoimmune and inflammatory diseases, and modulating the development and/or function of these cells for therapeutic purposes are of great interest. The conventional paradigm dictated that all Th17 cells differentiate from naà ...