Cardiovascular Disease

Cardiovascular disease—including heart attacks, congenital heart defects and many other disorders—is the world’s leading cause of death. Heart failure alone afflicts more than 23 million around the world.

Regenerating Hearts at Gladstone

Nobel at GladstoneIn the three decades that Gladstone has worked to overcome cardiovascular disease, our scientists have made significant progress against this devastating illness. We’ve conducted foundational research into the metabolism of cholesterol, for example, contributing to today’s understanding of how cholesterol and heart disease are linked—and how to use that information to prevent adult heart disease. We have mapped out molecules that direct the development of fetal hearts—unraveling how nature tells a cell to become a heart cell. This has profoundly changed our understanding of congenital heart defects—leading to Gladstone investigators’ discovery of genetic causes of heart disease and paving the way to future prevention.

And in the past several years, much of our work has expanded on the revolutionary discovery from Shinya Yamanaka, MD, PhD, who is formerly a Gladstone postdoctoral fellow and currently a Gladstone senior investigator. Dr. Yamanaka’s discovery—of how to transform ordinary adult skin cells into stem cells that, like embryonic stem cells, are capable of developing into any cell in the human body—has fundamentally altered the fields of developmental biology and stem cell research. For Gladstone cardiovascular research, we see this promising technology in two main areas: Dr. Yamanaka’s induced pluripotent stem cell, or iPS, technology shows amazing promise for the future of regenerating damaged hearts—and the modeling of disease as a way to better discover and test new therapies in the laboratory.

Thanks to iPS technology, for example, we can run drug tests on heart cells created from a patient’s own skin cells—cells that contain a complete set of the genes that resulted in the disease. In the area of regenerative medicine, Gladstone scientists have already transformed skin cells into beating heart cells in a petri dish. Just recently our researchers demonstrated how to make non-muscle cells convert directly into new muscle to repair damage in the hearts of live animals.

Certainly, the need for such breakthroughs is urgent. So we are working with purpose and focus on transforming such game-changing research into therapies that help doctors restore hearts damaged by heart attacks and disease.

A key part of our work at Gladstone is training tomorrow’s cardiovascular physicians and researchers. Our faculty are professors at the University of California, San Francisco (UCSF). They train our curious, passionate and determined graduate students, medical students and postdoctoral fellows—showing them how to approach complex problems from multiple points of entry. To learn more about training at Gladstone, please visit the Training Programs section of our website.

Featured Publications

Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S. (2014) Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor. Cell Reports 6:951­960. View in: PubMed
Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, Ding S. (2014) Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature. 508:93-97. View in: PubMed
Miyaoka Y, Chan AH, Judge LM, Yoo J, Huang M, Nguyen TD, Lizarraga PP, So PL, Conklin BR. (2014) Isolation of single-base genome-edited human iPS cells without antibiotic selection. Nat Methods. 11:291-293. View in: PubMed
Worringer KA, Rand TA, Hayashi Y, Sami S, Takahashi K, Tanabe K, Narita M, Srivastava D, Yamanaka S. (2014) The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes. Cell Stem Cell. 14:40-52. 3982312. View in: PubMed
Devine WP, Wythe JD, George M, Koshiba-Takeuchi K, Bruneau BG. (2014) Early patterning and specification of cardiac progenitors in gastrulating mesoderm. eLife. 3. View in: PubMed

Theodoris CV, Li M, White MP, Liu L, He D, Pollard KS, Bruneau BG, Srivastava DS. (2015) Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency. Cell. 160:1072–86. View in: PubMed

Yu C, Liu Y, Ma T, Liu K, Xu S, Zhang Y, Liu H, La Russa M, Xie M, Ding S, Qi LS. (2015) Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell. 16:142–7. View in: PubMed