Cardiovascular disease continues to be the leading cause of death in the U.S., claiming more than 900,000 American lives annually. High blood pressure, coronary heart disease (heart attack and angina), congestive heart failure, stroke, and congenital heart defects account for more deaths than all other major causes combined.

For more than 25 years, through its research and educational outreach programs, the Gladstone Institute of Cardiovascular Disease has been dedicated to reducing the loss of life and quality of life caused by these diseases.

In June 2005, Deepak Srivastava, MD, an internationally recognized cardiologist, developmental biologist and geneticist assumed the leadership of GICD. Before coming to Gladstone, Dr. Srivastava was professor of pediatrics and molecular biology at the University of Texas Southwestern Medical Center at Dallas where he held two endowed chairs and was co-director of the March of Dimes Birth Defects Research Center. His laboratory has made seminal contributions to the understanding of the molecular cues governing cardiac muscle formation from embryonic progenitor cells and in the genetics of human cardiac malformations and disease.

Dr. Srivastava will build on the solid foundation of excellence established by the founding director, Robert W. Mahley, MD, PhD. Currently, Dr. Mahley is president of The J. David Gladstone Institutes and continues as a senior investigator in GICD and the Gladstone Institute of Neurological Disease and as a professor of medicine and pathology at UCSF. He is a member of the National Academy of Sciences and the Institute of Medicine.

Cardiovascular disease is a complicated, multifactorial disease, and GICD emphasizes a multidisciplinary research approach. The research focus includes the following areas and is supported by three core laboratories.

Developmental and Stem Cell Biology. Studies in this area focus on determining the molecular and cellular cues that instruct a stem or progenitor cell to adopt the cardiac cell fate and then differentiate into cardiac myocytes. GICD investigators use mouse and human embryonic stem cell lines in an attempt to harness the potential of stem cell biology for cardiovascular therapeutics. Scientists in this group are also studying the three-dimensional morphogenesis of the heart to determine the underlying mechanisms of cardiac malformations that affect newborns and often have sequelae later in adulthood. This information will be vital to future attempts to fashion embryonic stem cells into functioning organs. Numerous model organisms are utilized, including mouse, chick and fruitflies, along with tools of molecular biology and biochemistry. The investigators in this area are Dr. Srivastava, Bruce R. Conklin, MD, Benoit G. Bruneau, Ph.D., and Shinya Yamanaka

Clinical Molecular Genetics. Patient studies and national and international population screening projects conducted by Gladstone researchers aim to identify unique genetic abnormalities that cause heart disease. These include genetic causes of common cardiac malformations and adult-onset calcification of cardiovascular tissue that contributes to disease. In addition, the genetic contributors of hypercholesterolemia and premature myocardial infarction are a focus in the GICD. Researchers operate the Lipid Disorders Training Center, which trains medical personnel to manage dyslipidemic patients, and the Lipid Clinic, which provides consultation on disease management to SFGH patients and to private, referring physicians. This unit also conducts the Turkish Heart Study, which investigates cardiovascular risk factors in a developing nation with a high incidence of heart disease. Dr. Srivastava, Thomas P. Bersot, MD, PhD, and Dr. Mahley are the investigators in this group.

Fat metabolism. Scientists in this unit apply the current techniques to understand the role of enzymes important in controlling cholesteryl ester and triglyceride production. This work has direct relevance for adipose tissue metabolism and obesity, one of the most significant health problems of the western world. Genetically altered mice are used to create animal models of human diseases and to understand the mechanism underlying fat deposition. Scientists in this area include Robert V. Farese, Jr., MD, and John M. Taylor, PhD.

Vascular Biology. This research aims to elucidate how monocyte/macrophages are attracted to sites of atherosclerotic lesion formation and to delineate the role of platelets in forming the occlusive thrombus that leads to myocardial infarction. Chemokine signaling is studied with respect to the atherosclerotic process. Another research goal is to elucidate cell-signaling pathways that can be used to confer proliferative advantages to genetically modified cells. The investigators in this unit are Israel Charo, MD, PhD, and Dr. Conklin.

Lipoprotein Biochemistry and Metabolism.A major focus of research in this area is to correlate the structure and function of the apolipoproteins involved in cholesterol transport, with particular emphasis on apoE.  One of the structural tools that scientists in this unit use is x-ray crystallography to determine the three-dimensional structures of proteins.  The investigators in this unit are Dr. Mahley and Karl H. Weisgraber, PhD.

Cell Biology of Cholesterol Deposition. Studies in this unit examine how the body’s various cells regulate the storage and use of cholesterol as it relates to the development of atherosclerosis.  The focus is on the roles of apoB, apoE, and class A scavenger receptors in cellular cholesterol metabolism and atherogenesis.  The investigators in this unit are Robert E. Pitas, PhD, and Yadong Huang, MD, PhD.

Gladstone Genomics Core.  The Genomics Core assists scientists with the unprecedented research opportunities presented by the decoding of the mouse and human genomes.  Directed by Christopher S. Barker, PhD, this laboratory provides state-of-the-art technologies in the area of functional genomics for Gladstone scientists and other investigators at SFGH.  The core focuses on DNA microarray technology, including the preparation of custom oligonucleotide microarrays and customized microarray hybridization, array scanning, and data analysis.

Gladstone Transgenic Core. The GICD also maintains a sophisticated transgenic core facility that is heavily used by investigators of all three institutes. The core’s activities are coordinated by Dr. Taylor.

Gladstone Microscopy Core.  The Microscopy Core, under the direction of Dr. Weisgraber, provides expertise, instrumentation, service, and training for the generation and capture of research data in the form of microscopic images and for the quantitation, analysis, and interpretation of those images to all three institutes.

Gladstone Stem Cell Core. The Stem Cell Core, under the direction of Dr. Conklin, is intended to expedite the vast potential of stem cell biology for human disease. The core provides expertise and training in the use and handling of mouse and human embryonic stem cells. In addition it provides technologies for encouraging stem cell differentiation into specific lineages for all three institutes.