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Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Biomedical Sciences ETDs
This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 …
Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini
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 …