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Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini

Biomedical Sciences ETDs

Through their ability to self-renew and differentiate, hematopoietic stem/progenitor cells (HSPCs) maintain the adult blood and immune systems. The microenvironment, or niche, in which HSPCs reside, serves as a critical regulator of HSPC functions. As previous work has identified the tetraspanin CD82 as a mediator of HSPC-niche interactions, we aimed to determine the mechanism by which this occurs. Our data demonstrate that CD82 expression and scaffolding regulate HSPC interactions with niche components by organizing the α4 integrin subunit into tightly packed nanoclusters. The HSPC niche can also protect acute myeloid leukemia (AML) cells from therapeutics. Therefore, we next examined how …

The Prohibitin Protein Complex Promotes Mitochondrial Stabilization And Cell Survival In Hematologic Malignancies, Elisa Robles Escajeda

Open Access Theses & Dissertations

Lymphocyte proliferation and differentiation is coordinated with high precision in healthy humans and is vital to maintaining a normal immune system. Imbalance of these events can result in the development of autoimmune diseases, immunodeficiencies and hematopoietic malignancies. These pathologies, specifically leukemia and lymphoma have a high incidence of relapse and mortality due to limited treatment options. Therefore, there is a critical need to characterize the signal transduction pathways and understand molecular hallmarks that mediate T cell activation in order to develop new strategies for diagnosis and treatments of these diseases.

Prohibitins (PHB1 and PHB2) have been proposed to play important …

Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder

Graduate School of Biomedical Sciences Theses and Dissertations

Leukemia is the most common childhood cancer, with a combined 40,000 predicted new cases in the United States in 2016 [8]. The two most common subtypes are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) [9-11]. The commercially available inhibitor of Bruton’s tyrosine kinase (BTK) has shown promising results in clinical trials for CLL because of the importance of BCR signaling in CLL [12-15]. Recent studies suggest that the outgrowth of BTK inhibitor resistant clonal cells in some CLL patients results in a treatment-refractory phenotype [16-18]. MALT1, a protein involved in BCR activation of the NF-κB pathway that functions …