Eric J. Topol, M.D.

Chief Academic Officer, Scripps Health
Director, Scripps Translational Science Institute
Sr. Consultant, Division of Cardiology, Scripps Clinic
Professor of Translational Genomics, The Scripps Research Institute

Cardiologist Eric Topol has done much to expand our understanding of how genetics can determine a person’s health risks. In his productive career as a physician-scientist, he has built an international reputation for his ground-breaking research and expertise. Click here to get a complete biography for Dr. Topol.|

Nicholas Schork, Ph.D.

Director of Research
Scripps Genomic Medicine Program

Dr. Nicholas Schork has the innate ability to place his talents at the right place at the right time. He was a graduate student at the University of Michigan in the late 80’s, studying philosophy and statistics, when the science of genomics was being born. Dr. Francis Collins, who would later head the Human Genome Project, was on the faculty at Michigan. When Dr. Collins mapped the gene responsible for Cystic Fibrosis, it opened a new world of possibilities. However, genetic researchers soon learned that analyzing the genome produced reams of data, and that information needed to be carefully analyzed to be useful. Dr. Schork was working at Michigan’s medical school when the need became apparent. While earning his Ph.D. in epidemiology, he helped provide statistical support for these early studies.

Later, Dr. Schork worked with Dr. Eric Lander, MIT, another genomics pioneer. In 1994, the two co-authored a paper called “The Genetic Dissection of Complex Traits.” Published in the journal Science, the article detailed different methods to determine the relationships between genes and disease. A milestone in the early study of human genetics, the paper is still widely cited.

Dr. Schork continued his work in both corporate and academic settings. In 2001, he was appointed to the faculty at UCSD. While this new position offered him access to excellent research facilities, what he needed most was a large genetic sample to study.

“The research I wanted to pursue had to do with collecting patient data, seeing what diseases they have, seeing if we can find the mechanism, seeing if we can overcome the defects, seeing if the drugs work,” says Dr. Schork.

When Dr. Eric Topol approached him with Scripps’ plans to use its large patient base to facilitate genetic studies, Dr. Schork was ready.

“Blockbuster drugs work in very few people,” says Dr. Schork. “There’s enough benefit to justify their use, but we need to identify the people they’re most useful for. How can we improve the use of those existing drugs? We need to find markers that distinguish the people who will respond and won’t respond. If you’re looking at millions of spots on genome that may be associated with particular diseases, then how do you separate the ones that are associated from the ones that aren’t? It’s either a statistical nightmare or a lot of fun, depending on your outlook.|

Sarah Shaw Murray, Ph.D.

Director of Genetics
Scripps Genomic Medicine Program

For Dr. Sarah Shaw Murray, going full circle has been an incredible trip. After earning her Ph.D. in human genetics at the University of Pittsburgh, Dr. Murray did her post-doctoral work at Case Western Reserve University, where she first worked with Dr. Nicholas Schork.

The technology she was using was primitive compared to what we have today. Genetic studies identify specific genes, often referred to as markers, locating them on their chromosome and comparing the variations in that gene between different people. Researchers analyze the genetic make-ups of thousands of people to find these variations, called SNPs (single nucleotide polymorphisms). The breakthroughs come when a genetic variation can be linked to a specific disease, and the more markers we can identify, the easier it is to make that link. When Dr. Murray first started in the field, there were 400 markers. Now there are close to a million.

Knowing more markers is especially important when trying to define the genetic causes of complex traits like diabetes, heart disease or schizophrenia. Because multiple genes play a cumulative role in each of these diseases, the effect of any one gene is minimal. Researchers needed new tools to analyze the genetic makeups of many people—quickly. As director of the Genotyping Science Group at Illumina, a San Diego biotech, Dr. Murray played a large role in developing that technology. Now, with micro arrays that can rapidly analyze as many as a million SNPs, researchers can get better information on individual genes, giving them the data to conduct complex statistical studies to determine how gene variations lead to complex diseases.

Though Dr. Murray had an important role in developing superior gene arrays, she was a bit wistful for lab work. Now that the technology had evolved sufficiently to decipher some of the fundamental relationships between genetics and disease, she wanted to be back in the trenches, using the technology she helped develop. The Scripps Genomic Medicine Program was the perfect opportunity. “I was making all these tools and looking at all these people doing such exciting work with these tools, and I wanted to be a part of it,” says Dr. Murray. “Our goal is not to publish a science paper, though I’m sure we will publish many. Our end game is taking this information and really helping to identify populations that will respond to specific drugs. But even that’s just the tip of the iceberg. We need to understand the metabolic pathways and enzyme pathways of disease and how to disrupt them.” |

Kelly Frazer, Ph.D.

Director of Genomic Biology
Scripps Genomic Medicine Program

Dr. Kelly Frazer gets so excited about human genetics, she can hardly keep still. Her hands weave complex geometric patterns as she talks about genes and how they function.

Dr. Frazer has been studying human genetics for more than twenty years and is only getting started. When she began, as a graduate student at the University of San Francisco, many of her colleagues did not even consider human genetics a science. Her first studies used a technique called radiation hybrid mapping, a method that combines living and dead cells to observe how DNA pieces combine. Compared to current technology, the technique was crude, but it taught us a lot about the human genome.

Later, Dr. Frazer worked at the Lawrence Berkeley National Laboratory, which sequenced chromosome five for the Human Genome Project, and most recently for Perlingen Sciences, Inc. as vice president of genomics. Like the rest of Dr. Topol’s team, Dr. Frazer is interested in learning how the genome functions. She notes that only about one percent of the genome codes for proteins. Another four or five percent is evolutionarily conserved, which means it has undergone little change in millions of years. So what does the rest do? Theories abound. For example, the DNA double helix is a very tightly wound package. So tightly wound, in fact, that it can only do its job if it opens up.

“In making it compact, you shut it off sometime,” says Dr. Frazer. “You can imagine that knowing when and where to open up involves function.”

Dr. Frazer acknowledges that there’s a great deal we do not understand about human genetics, which is one reason for her excitement. After years working in the lab, she now has the opportunity to apply her vast knowledge to helping patients.

“For the last twenty years, I’ve been working in human genetics and barely interfacing with doctors,” says Dr. Frazer. “To start translating this information, we really need to couple scientists with medical doctors so you can transition your findings into medicine. This is where we are headed. Scripps is just ahead of the game.”|