SB’s Entcheva explores a bright idea for arrhythmias

SB’s Entcheva explores a bright idea for arrhythmias

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Emilia Entcheva with her daughter, Anna Konova. Photo from Entcheva

What if a miniature tornado inside your chest threatened to kill you? What if, instead of waiting for a doctor or emergency worker to shock you with a defibrillator to restart your heart, doctors were able to use a series of lights to control that electric wave?

Emilia Entcheva, a professor of biomedical engineering at Stony Brook University, and Gil Bub from the University of Oxford, are in the early stages of understanding how to take just such an approach.

Working with cells in a lab, they used optogenetics, in which they directed a programmed sequence of lights on altered test cells, to see if they could affect this signal.

“We were able to speed up, twist and otherwise manipulate the electrical waves directly, using a computer-controlled light projector,” Entcheva said. They published their results recently online in the journal Nature Photonics, which will release a print version of the paper in December. “Because of the essential role of these waves in cardiac arrhythmias, this new approach suggests a completely different way of controlling these arrhythmias,” Entcheva said.

While using light to control cells presents a possible alternative some time in the future, the technique is far from any application in a human body, with scientists facing numerous, significant obstacles along the way, including how to get light into the body.

“The clinical translation to humans is not around the corner, but cannot be ruled out,” Entcheva said.

Still, as a concept, the field of optogenetics is showing promise. Thus far, neurologists have studied optogenetics for about a decade, while the field of researchers in cardiology using the same technique is smaller.

“People were taking a wait-and-see approach” with optogenetics and cardiology, said David Christini, a professor of medicine at Weill Cornell Medical College, who has known Entcheva for more than a decade and is collaborating on another project with her. “She was pretty bold in going after this and it proved to be a good move.”

Christini called the work Entcheva has done with optogenetics “groundbreaking” and said it was “of great general interest to the field.”

In optogenetics, most cells don’t typically respond to changes in light in their environment. The way scientists have altered this, however, is by inserting the genes that express a light-sensitive protein into the cell. The benefit of light-triggered channels over hormones or drugs is that the researchers can target individual cells or subcellular regions, while controlling the length of time these cells change their property. Researchers can also use different types of proteins to turn light activated switches on and off, potentially giving them additional control over these processes.

Entcheva started working on optogenetics around 2007, with graduate students in her lab. Her current postdoctoral researcher, Christina Ambrosi, and current doctoral students Aleks Klimas and Cookie Yu, as well as former students Harold Bien, Zhiheng Jia, John Williams and others contributed to this effort.

Entcheva, who paints nature scenes when she is not working, and described herself as a visual person, said the waves that determine heart rhythm can form a “spiral” that leads to an arrhythmia. “Like a tornado, such a spiraling wave can be quite destructive and even deadly,” she said.

When waves change from their normal path, they make the heart beat faster or irregularly, Entcheva said, which prevents it from working correctly.

To move these waves around, the scientists projected movies of light patterns using a technology that is common in projectors, called a digital micromirror device. A computer controls mirrors to affect the light they reflect at each point.

The light-sensitive proteins used in these experiments come from algae. Human cells don’t have them. Entcheva and her colleagues developed viruses that make cardiac cells start producing these proteins. Heart cells that express these proteins seem to act normally, other than developing a desired sensitivity to light, she said.

Entcheva and Bub had nightly Skype sessions while they conducted their transcontinental experiments. Bub said Entcheva was one of the “pioneers of the use of bioengineered cardiac tissues for the investigation of cardiac arrhythmia.”

Entcheva’s lab “did all the ground work developing ontogenetic constructs that made these experiments possible,” said Bub.

While Entcheva has been at Stony Brook since 2001, she plans to move to George Washington University at the beginning of 2016. “Stony Brook has been good to me, professionally and personally,” she said. “It helped me launch my academic career.”

She came to the United States 21 years ago from Bulgaria, after the Cold War ended. With a suitcase and $700 in her possession, she left her 10-year old daughter and husband at home. They joined her half a year after she arrived in Memphis. They couldn’t afford a car for a year, so they walked with their backpacks to Piggly Wiggly to buy groceries.

Her daughter, Anna Konova, followed in her mother’s scientific footsteps and is now a neuroscientist who studies the human brain in addiction. She works as a postdoctoral researcher at NYU.

As for the work Entcheva and Bub have done on optogenetics, Christini said they are “pushing the field forward in terms of implementing a tool that is of great value to biologists and experimentalists in illuminating and uncovering mechanisms of arrhythmias.”