Angel Baldan
Ph.D., University of Barcelona (Molecular Pathology)
Department: Biochemistry and Molecular Biology
Academic Rank: Assistant Professor
Phone: 314-977-9227 Fax: 314-977-9206
E-mail: abaldan1@slu.edu
Lab Web Page Links: http://biochemweb.slu.edu/people/faculty/baldan.shtml
Primary Area of Cardiovascular Research Interest
- Control of Sterol Homeostasis by miRNA. Impact on Atherosclerosis
Related Areas of Cardiovascular Research Interest
-Control of Pulmonary Surfactant by Sterol Transporters
-Macrophage Function: Atherosclerosis and Inflammation
-Hepatocyte Function: Lipoprotein Metabolism and Bile Excretion
Summary of Cardiovascular Research Interest
Altered cholesterol homeostasis lies at the base of multiple human disorders, including atherosclerosis and cholestasis. The transcription factors SREBP-2 and LXR have been proposed as “intracellular sterol sensors” that function to ensure the levels of these sterols are kept within a narrow, physiological window. In general, these latter proteins are thought to promote antagonistic, complementary transcriptional programs that stimulate cholesterol synthesis and uptake, or efflux, respectively. We have recently found a novel miRNA, miR-33, that is expressed from intron 16 within SREBP-2, and controls the expression of several classic LXR targets, such as the sterol transporters ABCA1 (essential for HDL lipidation and deficient in Tangier disease patients) and ABCG1 (also involved in HDL lipidation). Since patients with hypercholesterolemia (i.e. with high levels of plasma LDL-cholesterol) are usually put on Statins, and these drugs promote increased expression of SREBP-2, we anticipate that these patients will have increased levels of miR-33 in multiple tissues. Our main goal is to study the effects of altered miR-33 expression in liver and macrophages, two tissues that play key roles in multiple aspects of cholesterol homeostasis. Our current data suggest that the cholesterol–miR-33 axis controls key aspects of cell biology, sterol homeostasis, and lipoprotein metabolism. We are currently focused on experiments aimed at determining the role of miR-33 in reverse cholesterol transport from peripheral tissues to the liver, and in lipoprotein and bile metabolism. Ultimately, we hypothesize that modulation of miR-33 levels might offer a novel therapeutical approach to manage patients with hypercholesterolemia and/or intrahepatic cholestasis.
