Leukemogenesis, uncontrolled proliferation of dysfunctional, transformed immature lymphocytes, appears, especially in children, to be associated with abrogation of normal lymphopoiesis, and thymopoiesis in the case of T cell leukemias. Sequence specific transcription factors (SSTFs) are nuclear control switches that respond to cellular signals to alter cell state and cell fate...
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...
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...
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...
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 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...
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...
Herbs have been used for many centuries in diverse civilizations for the treatment of heart disease. Only a few natural supplements claim to have direct cardiovascular actions including hawthorn (Crataegus spp.) and berberine derived from the Berberidaceae family. Several different studies indicate important cardiovascular effects of hawthorn and berberine. For...
The mechanisms by which the activities of phospholipase C-β (PLC-β) enzymes are negatively regulated have not been well defined. We used cardiac-derived ratmyoblast H9c2 cells to investigate possible modes of regulation of PLC-β3 enzymes,the only endogenous β isoform abundantly found in these cells. The PLC-β3population in these cells was detected...
Adverse effects of anti-epileptic (AED) medications on bone density have been reported since the 1960s. Phenytoin and carbamazepine, two commonly prescribed AED, are frequently associated with osteomalacia including fractures and reduced bone formation. The mechanism by which AED induces bone loss is not fully explained. We sought to determine the...