At the University of Manitoba, researchers are zeroing in on a gene that kills heart cells
May 22, 2007
How do you mend a broken heart? Lorrie Kirshenbaum thinks he’s got the solution, and it doesn’t involve chocolate or flowers.

According to the University of Manitoba researcher, the answer lies in a powerful gene known as “Bnip3,” or “nip,” for short.

Five years ago, Kirshenbaum and his team cloned the nip gene, which they knew played an important role in the death of heart cells. Their research focuses on understanding the molecular signaling pathways in the heart that tell its cells when to live and when to die.

Kirshenbaum also refers to nip as the “death gene.” That’s because he’s discovered that decreased oxygen, which occurs during a heart attack, activates nip. Once nip is activated, the gene kills off heart cells.

Although there is a whole family of genes that cause cells to live or die, nip stands out because of its relationship to oxygen. Since heart attacks decrease the flow of blood carrying oxygen to the heart muscle, Kirshenbaum is figuring out ways to stop low oxygen from activating nip. That, in turn, would stop heart cells from dying, giving cardiac patients a better chance of recovery.

With such knowledge, “we could potentially design therapies to keep heart cells around longer,” explains Kirshenbaum, who is also an energetic and enthusiastic teacher.

Such therapies, likely delivered by modifying viruses to deliver specific genes to different cells, could revolutionize cardiac care. Eventually, Kirshenbaum hopes he and his fellow researchers around the world will harness nip’s properties and put them to work not only for cardiac patients, but for cancer sufferers too.

Cancer cells contain mutations that prevent them from dying. Essentially, they have lost their ability to stop dividing. They keep multiplying and form tumours. If researchers could activate nip within cancer cells, they could put the gene’s killing abilities to good use. Turning nip on would cause the cancerous cells to die before they multiplied. “We could put the death gene into potential cancer genes, as a way to block tumour formation and prevent the cancer from occurring,” Kirshenbaum says.

His work is an important step forward in the development of gene therapies that will modify heart and, eventually, cancer cells by manipulating them into living or dying to treat diseases.


Heart disease is the number one cause of death in North America. This places a major burden on the health care system, in part because people with heart failure require chronic therapies. By understanding what regulates the life and death of heart cells, Kirshenbaum and his research partners intend to design therapies to prolong the life of those heart cells. These gene therapies will improve heart function and reduce the treatment required for people with cardiac disease.

Kirshenbaum’s ultimate goal is “to prevent heart cells from dying.” In addition, the gene therapies could be applied to other diseases, like pulmonary hypertension, that influence oxygen delivery to the heart muscle. There is already some evidence that too much cell death affects the blood vessels in the lungs, impairing blood flow and oxygen. In the next decade, Kirshenbaum envisions emergency room physicians treating patients who arrive at the hospital in the throes of a heart attack, or those about to undergo bypass surgery, with an “anti-nip” gene. The therapy would stop their heart cells from dying and prevent further heart damage, in the same way that current therapies can reverse the effects of a stroke if they are applied soon after it occurs.


Understanding the role of crucial genes in the life and death of heart cells is a task that involves investigators at universities around the world. At the University of Manitoba, Lorrie Kirshenbaum understands the need for multidisciplinary work and collaboration to advance this science. One of his partners is Jennifer Hall, an assistant professor of medicine at the University of Minnesota.

As Kirshenbaum was piecing together the role of nip—the gene triggered by low oxygen to kill heart cells—Hall was concentrating on the role of another gene, known as “sprouty.” Sprouty is involved in inhibiting the heart’s function and size.

Sprouty and nip, the two researchers determined, talk to one another. Both are implicated in the process that causes heart cells to die, and regulate the heart’s response to cell deaths. Sprouty appears to induce cell death in both heart cells and blood vessels. Understanding the relationship between sprouty and nip is critical to helping researchers develop new drugs that will deactivate both genes, allowing the growth of new blood vessels and the preservation of heart cells.

“From a therapeutic standpoint, it may identify new drug targets to go after,” Hall says of her collaboration with Kirshenbaum.

Learn More

To find out more about Lorrie Kirshenbaum’s research visit his website at St. Boniface General Hospital Research Centre.