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Unveiling the secrets of the heart

Dr. Daniel J. Rader at his research lab at the University of Pennsylvania Medical Center.

Hidden away among piles of journals, books, and papers, in a hard-to-find office, in a hard-to-find building, on the campus of the University of Pennsylvania Medical Center, is an easygoing guy with a broad smile and infectious laugh who is on his way to making one of the greatest discoveries in the history of medicine: the cure for cardiovascular disease. His name is Dr. Daniel J. Rader '81, M.D.

Cardiovascular disease lurks behind the scenes of most heart attacks and strokes. "You hear a lot about cancer, a lot about HIV, a lot about other things, and they're all important problems," Rader says, "but they're dwarfed by this disease. Heart disease and stroke are the number one and number three killers in the U.S. and most of the world."

Rader specializes in the genetics of cholesterol metabolism and leads the field in developing new ways to raise blood levels of high density lipoproteins (HDL), the "good cholesterol." Low density lipoproteins (LDL) (the "bad cholesterol") deposit on the inner walls of your arteries and cause the formation of plaque, a condition called atherosclerosis, which can either thicken and block blood flow or rupture, causing life-threatening clots to form. On the other hand, HDL removes cholesterol from plaques and transports it back to the liver for removal from the body.

One obvious way to treat the condition is to reduce LDL levels in the bloodstream, but that's only half the battle. "Getting LDL cholesterol down to 70 or below is a pretty good way of preventing progression of the plaque," Rader says, "and we have good drugs to do that. But actually reversing atherosclerosis is the big goal. It's almost like the holy grail in the field."

Rader, with many of his colleagues, believes that raising levels of HDL could help reach that goal. But therapies that can do the job are still in the future.

"We don't yet have very good drugs to raise HDL, so that's been a major focus of my work," he says. "Right now in the HDL field, we are where we were in the LDL field about two decades ago, in the very early stage. We have some targets, some real legitimate places to start, but we need new drugs, and we need to test them and prove that they work. Once we've done that and then we combine lowering of the LDL with raising of the HDL, we're likely to see the rates of heart attack and stroke plummet."

That's more than just one researcher's pipe dream. Rader, who does basic scientific laboratory research as well as translational and clinical research at Penn, along with seeing patients one-half day per week, has already studied some novel approaches to solving the problem. A recent example involves a particular protein, called cholesteryl ester transfer protein (CETP), which normally siphons cholesterol out of HDL and therefore lowers HDL levels. The idea came from the discovery, more than a decade ago, of people in Japan who were genetically incapable of producing CETP and who had, on average, three times the normal levels of good cholesterol. As a result, CETP inhibitors were developed and Rader reported earlier this year in The New England Journal of Medicine their results with a CETP inhibitor in patients with low HDL levels.

"When we gave our patients the CETP inhibitor in this study, their HDLs more than doubled," Rader says. "It was really nice to see, and the patients were thrilled. But that was a short-term study. Now the question is whether CETP inhibitors actually reduce the risk for heart attack or stroke. From all we know, they should. But that's a study you just can't do in a couple of months. In fact, it will take several years. So that's kind of where we are now. If the results turn out to be positive, we'll have a tool that can make a big impact on public health."

Rader is involved in several other studies of novel HDL-raising therapies as well.

Mixing medicine and music

Dr. Rader's research focuses on lowering cholesterol.

Rader grew up in a suburban community, among the cornfields and country roads outside of Lancaster, Pennsylvania. His father, Glenn, was a minister in the United Church of Christ, and his mother, Janet, now deceased, was a nursery school teacher, although she was much better known locally for her singing. She had starred in both operas and musicals in the Lancaster area and passed on her vocal talents to her son, who has maintained a deep love of music all his life.

In school, Rader excelled in science and mathematics, but he also enjoyed interacting socially with other people. He wasn't sure which of those stars to follow. By his senior year of high school, he had begun to toy with the idea of becoming an engineer, but his mother came up with a more intriguing idea: Becoming a doctor might be a way to combine his love of science with his love of people.

When Lehigh accepted him into its BA/MD program, which would allow him to earn his bachelor's degree in two years and then guarantee him a spot at the Medical College of Pennsylvania (MCP), his mind was made up.

As it turned out, Lehigh had much more to offer Rader than a great education in science. It also gave him the opportunity to follow his other lifelong passion: music.

"I was on campus for only two years," he says, "and during that time, music was my avocation. When I was a freshman, I sang in the Lehigh Glee Club. That year happened to be the glee club's last. The administration had basically said 'no more all-male or all-female glee clubs. We're going to make a bigger choir and put everybody together next year.' So we had an amazing season. Bob 'Boss' Cutler, who was the musical director and sort of a mythical figure in the choral world, booked maybe three times as many concerts that year as the glee club had ever done before. Then we had an unbelievable concert at the end of the year."

The mixed chorus began the following autumn, and Rader was elected its president. "It was Boss's last year before retiring. We threw a tremendous surprise retirement party for him, which I helped organize. I also played in the orchestra, directed by Jerry Bidlack. My instrument was string bass, which I'd been playing since the third grade. I also took organ lessons from Jerry, and served as an organist for a small church in Bethlehem."

After completing his second year, Rader didn't feel he was quite yet ready for medical school, so he took advantage of a junior-year-abroad program and spent a year in Munich, Germany. The trip allowed him to relax his priorities a little.

"I had a great time," he says. "It was the one period of my life when academics wasn't the major thing for me. I really didn't study much at all, and often didn't even go to classes, but I did a lot of music. I sang in the chorus of one of the smaller opera houses in Munich, and I sang in another chorus that also did concerts."

After graduating summa cum laude from Lehigh, Rader moved to Philadelphia and joined a large chorus called Singing City. He also started his medical career at MCP.

During that first year, Rader discovered the work that remains his greatest passion to this day. "I worked at the lab="mailto:jacm@lehigh.edu">--E.A. Tremblay

Lehigh Alumni Bulletin
Winter 2005


Posted on Friday, January 21, 2005

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