Profiles in research: Guido J. Falcone M.D., Sc.D., M.P.H.

Spontaneous intracerebral hemorrhage happens when a weakened vessel ruptures in the brain. It’s the most devastating stroke type. Nearly one-third of intracerebral hemorrhage patients die in the hospital and only one-third regain functional independence.

A neurologist also trained as a genetic epidemiologist, Guido J. Falcone M.D., Sc.D., M.P.H., has made it his goal to not only uncover common genetic mutations in intracerebral hemorrhage patients, but also better understand how the risk of this disease differs among ethnicities. The foundation of his research is today’s largest collection of genetic studies of intracerebral hemorrhage.

“The world of genomics and genetics has changed. It used to be that we thought DNA was a static thing and a mutation was a rare occurrence, and that people who had a mutation had a disease,” said Dr. Falcone, assistant professor of neurology at Yale School of Medicine.

Today, scientists know otherwise. Mutations aren’t rare and people who have them might be at higher disease risk but not ever get the disease. “What we know now is that if you look at the general healthy population, there are about 50 million common variations in our genome, also called common genetic variants. My research focuses on understanding how these common genetic mutations influence the occurrence, severity and recurrence of stroke—particularly intracerebral stroke,” Dr. Falcone said.

He aims to establish an association between one or more of these common mutations and intracerebral hemorrhage.

“That can tell us two things: by looking at the protein that is coded by the gene that contains the mutation, we can identify new biological mechanisms underlying the occurrence of intracerebral hemorrhage. And we can also use this genetic information to find new pathways to treat this type of stroke,” according to Dr. Falcone. “Once we identify one of these mutations, we can look at a combination of these mutations and try to gauge a person’s risk even before that person has the disease. That’s the world of precision medicine.”

Dr. Falcone has no plans to do his research in a vacuum. His goal, in fact, is to democratize the data, creating an open-source pipeline that make the information and tools to process it freely available investigators so they, too, can do research.

Dr. Falcone’s datasets of genomics and intracerebral hemorrhage are vital to stroke research also because they include different ethnicities. “Most genetic research so far has been done in whites. The data we’ll be working with contains almost equal portions of whites, blacks and Hispanics,” according to Dr. Falcone. “That’s important because we cannot assume that connections between mutations and disease identified for whites apply to other races.”

In fact, researchers already know the risk for intracerebral hemorrhage is not equal across races. The stroke type is more common among African Americans. The most important risk factor for intracerebral hemorrhage is hypertension, and this racial/ethnic group have a higher prevalence of hypertension.

This research could revolutionize the field of minorities’ research in intracerebral hemorrhage genetics by collecting, harmonizing and publicly sharing the largest trans-ethnic collection of genetic studies looking at this devastating disease to date, according to Dr. Falcone.