BCL11B, a gene regulatory transcription factor, is known to be a regulator of T cell development in the immune system, and has been identified as a tumor suppressor for T cell leukemias. Defining the molecular events that regulate the activity of BCL11B will provide potential drug targets that will aid...
Thymocytes, cells of the thymus gland, undergo developmental steps that
enable them to properly mature into T-cells. Errors in gene expression may lead to
improper maturation and potentially mass proliferation of dysfunctional thymocytes,
a hallmark of leukemia or lymphoma. BCL11B is a tumor suppressor and
transcriptional regulatory protein that is...
Phospholipase C-β (PLC-β) isozymes are key effectors in G protein-coupled
signaling pathways. Prior research suggested that some isoforms of PLC-β may exist
and function as dimers, but little is known about dimerization of PLC-β. Data from coimmunoprecipitation
assays of differentially-tagged PLC-β constructs and sizeexclusion
chromatography of native PLC-β support homodimerization...
Phospholipase C enzymes hydrolyze the rare membrane lipids phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) PIP into inositol triphosphate (IP3) and diacylglycerol (DAG). Phospholipase C enzymes of the β subtype (PLC-β) function specifically in the signal transduction pathways regulated by Gαq-coupled seven transmembrane receptors. These signaling pathways link plasma membrane receptor activation...
Atrial fibrillation is the most common cardiac arrhythmia, and the mechanisms that lead to this heart defect are not fully understood. Consequently, treatments for this defect do not currently reverse structural or molecular variations that lead to cardiac arrhythmia. Loss of the gene coding for the transcription factor Pitx2 leads...
Immature T cells, known as thymocytes, undergo development through successive stages in the thymus and the periphery to become functional mature T cells. These stages are regulated by sequence specific transcription factors (SSTFs). Two such SSTFs, BCL11B and TCF-1, are both known master regulators of thymopoiesis, which is also known...
The purpose of this honors thesis research project is to investigate the molecular causes of childhood and infant T-cell acute lymphoblastic leukemias. T-cells are the work horses of the immune system, and like any organ, must develop properly to be fully functional. Improper development of thymocytes into T-cells can lead...
Long-term stimuli of many systems leads to decreased cellular responsiveness, or desensitization. We characterized the desensitization of angiotensin II (Ang 11)-mediated inositol phospholipid (IP) hydrolysis in cultured human aortic smooth muscle cells (HASMC). Although it has been suggested that the desensitization induced by long-term Mg II exposure may result partially...
The experiments explained in this Honors thesis are focused on finding a cellular model for analyzing Bcl11b, a transcription factor dysregulated in 20% of cases of T-cell Acute Lymphoblastic Leukemia (T-ALL). Acute Lymphoblastic Leukemia is the most common childhood cancer. Because T-ALL is a result of incorrect thymocyte development, research...
Phospholipase C-Jβ (PLCβ) is an important effector enzyme in G-protein-coupled
signaling pathways. Activation of PLCβ by Gα and Gβy subunits has been fairly well
characterized, but little is known about other protein interactions that may also
regulate PLCβ function. A yeast two-hybrid screen of a mouse brain cDNA library
with...