Regulation of the Hepatic LDL Receptor and PCSK9:
High levels of LDL are well known to be associated with an increased risk for atherosclerosis. The key atherogenic property of LDL particles involves the formation of the atherosclerotic plaque. Since the hepatic LDL receptor is the major determinant of plasma LDL-cholesterol levels, direct regulation of the LDL receptor gene by factors such as cholesterol biosynthesis inhibitors, currently used to treat hypercholesterolemia, and hormones such as thyroid hormone and insulin, is expected. PCSK9 is a convertase that control the protein expression of the hepatic LDL receptor. The goal of our research is to characterize the molecular mechanisms involved in the regulation of the LDL receptor and PCSK9 genes.
Role of Hypothyroidism on Alzheimers Disease:
Alzheimers disease is a progressive neurodegenerative disorder that currently affects more than 18 million individuals worldwide. Among the risk factors that have been described for this disease is hypothyroidism, the second most common endocrine disorder in America. Thyroid hormone plays a key role in the development and maintenance of basal forebrain cholinergic neurons typically involved in Alzheimers disease. Furthermore, in vitro studies have shown that thyroid hormone regulates the expression of the APP gene, the precursor of A?, and the splicing of Tau protein at exon 10. Our goal is to determine whether there is a direct relationship between hypothyroidism and the appearance of Alzheimers disease markers.
Role of Hypothyroidism on Breast Cancer:
Breast cancer is the most common cancer among women and the second leading cause of cancer deaths in women after lung cancer. Extensive research is currently underway to identify agents that could induce apoptosis in breast cancer cells facilitating therapeutic intervention and potentially improve outcomes for breast cancer patients. A hormone that could be useful in the induction of apoptosis in breast cancer cells is thyroid hormone. Hypothyroidism and low-normal free thyroxine are related with an increased risk of breast cancer in post-menopausal women and with a reduction in the response to treatment. In this project, we are concentrating in determining the mechanisms involved in the control of breast cancer cell proliferation by thyroid hormone.