Broad scientists win innovation, transformative research grants

Five scientists from the Broad Institute and its partners have won federal grants to pursue projects with the potential to transform scientific research and more rapidly bring biomedical advances to patients.

The National Institutes of Health is awarding approximately $155 million to 81 researchers across the country who are pursuing visionary science through its High Risk High Reward program, supported by the NIH Common Fund.

Feng Zhang, Broad core faculty member, an assistant professor at MIT in the departments of brain and cognitive sciences and biological engineering, and an investigator at the McGovern Institute for Brain Research at MIT, has won one of 10 NIH Director's Pioneer awards for a project titled "Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome Engineering." Emily Balskus, Broad associate member and assistant professor of chemistry and chemical biology at Harvard, has received one of 50 New Innovator awards for "Biocompatible Chemistry for In Vivo Metabolite Modification."

Zhang is also one of four key investigators in a seamless partnership spanning the Broad, Harvard, MIT, Massachusetts General Hospital, and Brigham and Women's Hospital. A five-year Transformative Research Project award has been made to the team, which is also jointly led by David Altshuler, founding core faculty member at the Broad and professor of genetics and of medicine at Harvard Medical School and at Massachusetts General Hospital; Chad Cowan, assistant professor of stem cell and regenerative biology and co-leader of the Harvard Stem Cell Institute's diabetes program; and Kiran Musunuru, assistant professor of stem cell and regenerative Biology at Harvard University and an associate physician at Brigham and Women's Hospital.

Together their project aims to create better tools to better understand type 2 diabetes and heart attacks by doing experiments on human embryonic stem cells engineered to carry specific genetic mutations found in patients with these diseases. Diabetes affects 300 million people around the world, according to World Health Organization estimates, and heart attacks are the leading cause of death in the world.

The team will exploit recent advances in next-generation sequencing studies to read DNA, identifying potentially important genetic mutations in these common diseases. They will also build on innovative work by Zhang that makes it possible to edit the DNA of a patient. This will allow them to introduce any number of mutations into a human embryonic stem cell that has been transformed into one of four types of cells important in diabetes and heart attacks: muscle, fat, liver, and insulin-producing pancreatic beta cells.

Their hope is these human cells will make it possible to connect genetic mutations to defects in cell biology that result in patients' disease. Engineering human stem cells in this fashion offers the potentially major advantage of isolating genetic mutations that contribute to diabetes or heart disease, without having to tease out other, confounding factors.

The ultimate goal is to use this knowledge to improve therapies for diabetes and heart attacks.

"If successful, this has the potential to augment some of the studies currently done in animal models with comparably powerful human experimental studies," Altshuler said. "We hope that will translate in the long run into being able to treat or prevent these diseases in humans."

The goals are ambitious and potentially applicable to other diseases, Altshuler said, making the project ideal for the NIH program.

"The Common Fund High Risk High Reward program provides opportunities for innovative investigators in any area of health research to take risks when the potential impact in biomedical and behavioral science is high," NIH Director Francis S. Collins said in a statement announcing the awards.