Areas of Investigation

At Gladstone, we attack the whole spectrum of cardiovascular disease—from congenital heart disease that children are born with to acquired, adult conditions such as congestive heart failure. Our weapons against these illnesses include developmental, chemical and stem cell biology, as well as genomics. With these approaches, combined with ongoing advancements in the study of obesity, we have created a rich and fertile environment for advances in human health.

For example, Gladstone scientists are unraveling every biological step in the embryonic development of a human heart in order to see what genes, RNAs or proteins can be targeted as a way to prevent or treat congenital heart disease. We are also working on showing how changes in the structure of chromosomes are vital for heart development, and to determine how immune cells contribute to the build-up of plaque in arteries. We are working on ways to improve the reprogramming of human skin cells into heart cells, while we investigate how cells form lipid droplets—which are essential for storing fats and providing energy to the human body. We are also investigating the most rapidly evolving areas of the human genome as a way to improve our understanding of human disease and evolution.

Many of our areas of research build on the pioneering stem cell work of Gladstone Senior Investigator Shinya Yamanaka, MD, PhD. After completing his postdoctoral training at Gladstone, Dr. Yamanaka went on to discover a revolutionary technology for transforming ordinary adult skin cells into stem cells that, like embryonic stem cells, are capable of developing into virtually any cell type in the human body. His discovery of induced pluripotent stem cells, or iPS cells, has since revolutionized the fields of developmental biology and stem cell research, opening promising new prospects for the future of both personalized and regenerative medicine.

While Dr. Yamanaka achieved his iPS breakthrough by introducing four factors into adult cells, at Gladstone we’re working on additional ways to transform adult cells into stem cells—such as with chemical compounds. And rather than using such compounds to reprogram cells all the way back to the pluripotent state, we are also working on more direct ways to transfer one type of cell directly into another. For example, we are reprogramming cardiac fibroblasts—the heart’s connective tissue—directly into beating cardiac-muscle cells. We are also using cellular reprogramming to create heart cells from skin samples of patients with many cardiovascular diseases, such as calcification of the aortic valve, in order to test the safety and efficacy of new or existing drugs to treat or prevent the condition.