The researcher who ranked No. 6 among all U.S. neurologists in funding from the National Institutes of Health in 2013 is right here at the University of Cincinnati Neuroscience Institute. Daniel Woo, MD, MS, was propelled to that position by outstanding mentors, a brilliant theory, and a determination to advance science in a way that would help thousands of people he would never meet.

Dedicated to unraveling the genetic and environmental risk factors for intracerebral hemorrhage, a life-threatening type of bleeding stroke, Dr. Woo is principal investigator of three studies that were collectively funded at $5.65 million in 2013: the Genetics and Environmental Risk Factors of Hemorrhagic Stroke (GERFHS) study, the Ethnic/Racial Variations with Intracerebral Hemorrhage (ERICH) study, and the Stroke Genetics Network (SiGN) study.

Dr. Woo, Professor of Neurology and Rehabilitation Medicine and a member of the UC Comprehensive Stroke Center at the UC College of Medicine and UC Health, earns another accolade today as he assumes the role of Vice Chair of Clinical Research in the Department of Neurology. The announcement was made by Brett Kissela, MD, MS, Professor and Albert Barnes Voorheis Chair. In his new role, Dr. Woo will work with Kim Seroogy, PhD, Vice Chair of Basic Research, to advance scholarly activity and research within the department.

After graduating from the University of Virginia in 1990, Daniel Woo came to Cincinnati as a medical student, following a young woman he planned to marry. The relationship soon fizzled, but a lifelong passion for neurology began.

Dr. Woo vividly remembers a scene during his first year, when he and a few other medical students watched the legendary Thomas Brott, MD, conduct a neurologic exam. “I remember that he had never seen this patient before,” Dr. Woo says. “We examined the patient, and because of the way the patient’s eyes were moving and how one side of the face was weaker, Tom predicted the lesion would be in a specific location and what it would look like. He even drew a little picture. I remember that I was a little skeptical. And then he showed us the CT scan, and he was exactly correct. It wasn’t a huge stroke; it was a smaller stroke in a smaller location in the brain, and he had identified it perfectly. And that was it: I was hooked on neurology. I was fascinated by that.”

“I want to be like that guy someday.”

Two years later, during his neurology rotation, Dr. Woo studied under Joseph Broderick, MD, then a rising neurologist and today the internationally known Director of the UC Neuroscience Institute. “Joe was a young academician, but he had this wonderful bedside manner, really bringing medicine to patients so that they understood what he was saying,” Dr. Woo says. “I remember thinking, ‘I want to be like that guy someday.’”

After graduating, Dr. Woo did his residency at the Cleveland Clinic and then returned to UC for fellowship training in 1998. A native of Washington, D.C., he expected to stay in Cincinnati a year. But Drs. Brott and Broderick had recently pioneered the first effective treatment for acute ischemic stroke, a development that brought heightened prestige and energy to the program. Administered within a few hours of the stroke’s onset, tissue plasminogen activator (TPA) could break up clots that were blocking blood flow to the brain. Suddenly, people who previously would have died or become disabled by stroke were returning to their normal lives.

Dr. Woo witnessed such a recovery when he treated Zoltan Balogh, a math professor at Miami University who had collapsed from a massive stroke while riding his bike. “We flew him down here, and there was a big clot in the right side of his brain,” Dr. Woo recalls. “We cleared the clot very quickly. Less than three months later he solved a math problem he had been working on since the 1960s. It was a great feeling to make an impact like that.” People Magazine’s story about Professor Balogh hangs framed in Dr. Woo’s office.

Still, Dr. Woo sought something larger.

“During my fellowship year I realized, ‘I’m a fine doctor and I take very good care of my patients.’ But what Joe and Tom did when they brought TPA into the world was to help thousands of people they had never met before. I remember thinking to myself, ‘I’d like to do something like that. I’d like to use my wits and brains to make that kind of contribution to help people. To advance science like that would be tremendous.’ ”

A theory takes root

By 2001 Dr. Woo had developed a theory, based on his observations, about high blood pressure (hypertension). “Whether your blood pressure is 180 over 100, or 120 over 80, your brain wants exactly the same amount of blood flow,” he says. Regulating the amount of blood flow can be a challenging task for the brain, which is unique in its vascular design. Elsewhere in the body, large blood vessels branch into ever smaller vessels, so that the pressure on the main vessel is widely distributed, Dr. Woo explains. But in the brain, which developed rapidly during evolution, very small vessels come off the main trunk “like alleys off an interstate.” These sensitive junctures are where hypertensive strokes tend to occur.

Dr. Woo theorized that some people are well equipped to handle blood flow regulation, while others have a flaw in their DNA that makes them more at risk of mishaps, i.e., an intracerebral hemorrhage, or ICH. Only 60 percent of the risk for ICH can be attributed to high blood pressure and behavioral factors such as smoking and excessive alcohol consumption, Dr. Woo says. The other 40 percent remains unexplained.

With this theory in mind, Dr. Woo secured a career development grant from NIH and earned a master’s degree in molecular genetics at UC. His next step was to acquire the grants needed to pursue his theory. He was stunned to discover that although African Americans had twice the incidence of ICH as whites and suffered those hemorrhages an average of 10 years earlier, the nation’s repository of strokes contained only 170 ICH cases for blacks, compared with 2,000 for whites. Probing further, he found that the database contained fewer than 100 cases for Hispanics, who have almost double the incidence of ICH and tend to have strokes 7 to 10 years earlier than whites.

“We had known for 20 years that these differences existed,” Dr. Woo says, “and yet we had never collected the samples.”

The stars align for a “big-picture grant”

That would change. In October 2008, as Dr. Woo watched the presidential debates, he began connecting dots. He recalls thinking, “Barack Obama is going to win the presidency. This might be a good time to write a minority grant.”

NIH was still flush with grant money at that time, and grant submissions could run up to 25 pages (rather than the current 12), an advantage for a complex, multi-million-dollar “big-picture grant” like the one Dr. Woo envisioned. “I wanted 1,000 black ICH cases in the study and 1,000 Hispanics. And for comparison, I wanted 1,000 whites. I wanted to do the study correctly.” Using a population density heat map from the 2000 U.S. Census, Dr. Woo identified collaborators from academic health centers in major population centers and invited them to participate.

In a rare development, Dr. Woo’s grant was lauded, approved and funded on its first submission. And in 2010 the Ethnic/Racial Variations with Intracerebral Hemorrhage (ERICH) study was launched. Twenty of America’s most prestigious research institutions would participate.

What the researchers find, Dr. Woo says, could help people of all races. “Let’s say African Americans have a genetic predisposition to high blood pressure’s effects on the brain and they are more likely to suffer a hemorrhage. If we find what causes that to happen and can treat it, then we can treat everybody.”

He notes that statins, the cholesterol drugs, were discovered through research into a genetic defect that caused some people to have inordinately high levels of cholesterol. “But today anybody with high cholesterol takes statins, and practically none of them have the defect,” he says.

Results of ERICH have not been published, which means that any medication to reduce the risk of ICH is still a long way off. But the rails for that journey have been set.

“If I’m right, we will have something we can say made a big difference for patients at risk of hemorrhage,” Dr. Woo says. “It would be great. It would mirror something that I said about Joe Broderick when he brought TPA to the world: He helped thousands of people. It’s a great thing to accomplish in your career.”

– Cindy Starr