NHLBI grants will fund use of iPS cells to study insulin resistance and pulmonary hypertension

Marlene Rabinovitch

Two School of Medicine research teams have received funding from the National Heart, Lung and Blood Institute to use lab-made stem cells to study human disease.

One team — led by Marlene Rabinovitch, MD, professor of pediatric cardiology; Michael Snyder, PhD, professor and chair of genetics; and Joseph Wu, MD, PhD, associate professor of medicine and of radiology — will study a life-threatening lung disease. The other team — led by Thomas Quertermous, MD, professor of cardiovascular medicine, and Eric Schadt, PhD, chair of genetics at the Mount Sinai School of Medicine in New York — will examine insulin resistance.

Instead of isolating stem cells from embryos or umbilical cords, scientists can now create stem cells from adult tissues, such as the skin. The so-called induced pluripotent stem cells can then be transformed into a growing collection of cell types, including varieties that are otherwise difficult to obtain, such as neurons or blood vessel cells. The technique can be particularly useful for studying diseases with a genetic or other inheritable basis because an iPS cell and its offshoots carry the same genes that contribute to disease in the individual.

“The iPS cells really open up a new vista for us to be able to correlate cellular behavior to what we see in terms of individual risks for human disease,” said Quertermous.

Quertermous will receive $9.2 million over five years to study the genetic and cellular basis of insulin resistance. Insulin is a hormone that regulates how sugars and fats are burned and stored in the body. In a growing proportion of the U.S. population, the body begins to resist insulin’s signals, leading to diabetes and heart disease.

Thomas Quertermous

“Insulin resistance is probably the largest medical problem we face in the developed world,” said Quertermous. “We have very few tools to identify people who are insulin-resistant, and we don’t have drugs that can treat them just yet, so the need for information about this problem is gigantic.”

Quertermous and his lab will create iPS cells from hundreds of patients that represent the whole spectrum of human sensitivity to insulin. The nearly unlimited supply of cells will aid their search for the cellular basis for insulin sensitivity and therapeutics. “These cells will provide the opportunity to investigate compounds that might facilitate the cell’s ability to use insulin,” he said.

Rabinovitch, Snyder and Wu will receive $9.1 million over five years to study the inherited causes of pulmonary hypertension, a condition of abnormally high blood pressure in the arteries of the lungs that can lead to heart failure. The disease can affect patients as young as infants, and women are more than twice as likely to be affected. “Therapies are not curative and so the disease often leads to heart failure, necessitating lung transplantation,” said Rabinovitch.

The researchers will create blood vessel cells from patients with pulmonary hypertension to explore the hereditary causes of the condition. Key to the study is a collaboration with the Pulmonary Hypertension Breakthrough National Network, which will enable the Stanford team to work with cells from diseased lungs that were removed during a transplant operation. “The studies proposed will not only help uncover the genetic basis for pulmonary hypertension but will improve our understanding of the biological basis of the disease, which is necessary to develop diagnostic tools and personalized treatment strategies,” said Rabinovitch.

Seven other U.S. groups will also receive funding from the NHLBI, which is part of the National Institutes of Health, for iPS cell work. The grants were announced July 13.