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Gating Mechanisms Of The Canonical Trp Channel Isoform Trpc4, Dhananjay P. Thakur Aug 2015

Gating Mechanisms Of The Canonical Trp Channel Isoform Trpc4, Dhananjay P. Thakur

Dissertations & Theses (Open Access)

Non-selective cation channels formed by Transient Receptor Potential Canonical (TRPC) proteins play important roles in regulatory and pathophysiological processes. These channels are known to be activated downstream from phospholipase C (PLC) signaling. However, the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. Uniquely, TRPC4 is maximally activated only when two separate G protein pathways, Gq/11 and Gi/o, are co-stimulated, making it a coincidence detector of Gq/11- and Gi/o -coupled receptor activation. Using HEK293 cells co-expressing mouse TRPC4β and selected G protein-coupled receptors, I observed that coincident stimulation of Gi/o proteins and …


Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith Aug 2015

Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith

Dissertations & Theses (Open Access)

Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – …


Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen Aug 2015

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations & Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …