Johns Hopkins Gazette | April 27, 2009
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The newspaper of The Johns Hopkins University April 27, 2009 | Vol. 38 No. 32
 
Genetics Fuels New Initiatives

Framework for the future grants seed two programs

By Greg Rienzi
The Gazette

A duo of university initiatives seeks to significantly alter the medical landscape in terms of disease research and patient treatment by combining the latest in genetic science with good old-fashioned Johns Hopkins know-how.

Discovery grants seeded both initiatives. A program in computational genomics has already blossomed into a center, while an effort to pioneer individualized medicine has firmly taken root and spawned a steering committee.

The programs were among the 11 inaugural grant winners out of 74 proposals submitted to the Framework for the Future's Discovery Working Group. Each of the 11 selected initiatives received startup funding of up to $200,000 per year for up to three years. The university hopes that these Discovery grants will ignite new areas and strengthen existing ones where crossdisciplinary interactions make a major difference.

The Discovery Working Group is one part of Framework for the Future, a strategic planning process that then Provost Kristina Johnson and President William R. Brody initiated in May 2008. The other two are Ways and Means, and People.

From their Discovery grant proposal "Nucleating a Discipline: Creating Leadership in Bioinformatics and Computational Biology," faculty from the schools of Arts and Sciences, Engineering, Medicine and Public Health have recently organized the Johns Hopkins Center for Computational Genomics, which will officially launch its work next month.

The new center looks to extend the work of the university's Genome Café — a genome biometry laboratory housed in the School of Public Health's Department of Biostatistics — and the Genomic Integration Across N Technologies (GIANT) working group, which facilitates interactions among people trained in statistics, bioinformatics, computer science, biostatistics and medicine.

Sarah Wheelan, assistant professor of oncology biostatistics and bioinformatics at the School of Medicine and the center's initiating principal investigator, said that high-throughput technologies such as microarrays generate unprecedented amounts of highly interconnected biological and clinical data, whose interpretation requires pioneering and multidisciplinary approaches. The emergence of these new technologies has made it seemingly impossible, she said, for a single person to conceive, direct, perform and interpret a modern large-scale experiment.

The center looks to bring together the expertise needed to take advantage of these new data sets that promise breakthroughs in disease research. Through training and by facilitating collaboration, the center seeks to enable an investigator to correctly interpret and make use of a much larger fraction of his or her data. Prominent bioinformaticians estimate that out of any given biological or clinical experiment, only a fraction of the potential biological discoveries are made when the data are analyzed with standard techniques by a nonspecialist.

"The average biologist can't make a dent analyzing all this complicated information, and the average statistician doesn't have the biological intuition to follow up on leads presented by the results," said Wheelan, who has a joint appointment in Biostatistics in the School of Public Health. "There are not enough people who have both biological and statistical knowledge to direct these experiments and clinical trials. The center will provide this hybrid training and foster collaboration that will allow us to more effectively attack biological problems using statistical and computational approaches."

The Johns Hopkins Center for Computational Genomics will encompass three interacting entities: a research center, a graduate education program and a program in skills development for professionals. The core staff are Wheelan; Rafael Irizarry, a professor of biostatistics at the School of Public Health; Luigi Marchionni, an instructor of oncology at the School of Medicine; and Jonathan Pevsner, an associate professor at the Kennedy Krieger Institute and of neuroscience at the School of Medicine.

It will be housed in the Preclinical Teaching Building on the East Baltimore campus. The center's Web site, genomics.jhu.edu, is currently under construction.

A three-year grant also dealing with genetics was given to a proposal in individualized medicine submitted by faculty and staff from the Applied Physics Laboratory, the Berman Institute of Bioethics and the schools of Arts and Sciences, Medicine and Public Health.

David Valle, director of the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins and a principal member of the newly founded Johns Hopkins Individualized Medicine Program, looks to shake up the one-size-fits-all approach to medicine and usher in a new era where physicians treat a person based on his or her genome and environmental factors.

"Since the earliest days of medicine, physicians have been educated in terms of generalities. In a sense, standard medicine is average medicine; not to say it's mediocre, but that it's based on a law of averages," Valle said. "You'll learn here is what happens with a patient with pneumonia. But once you get into practice, you don't see generalities; you see a specific person with pneumonia. When you talk with experienced physicians, very often you come to the realization that no two patients are exactly alike."

While the genomes of any two people are 99 percent identical, the minute genetic variations in the 3 billion DNA letters can make the difference between a person who needs five times the average amount of a certain drug to someone for whom the average dose would be unsafe.

The Johns Hopkins Individualized Medicine Program looks to take advantage of recent advances in genetics, fueled by the completion of the Human Genome Project in 2003 and the HapMap Project, a multicountry effort to identify and catalog genetic similarities and differences in human beings. To date, HapMap has identified up to 90 percent of the common genetic variation in humans.

Valle said that the evolution of genotype technology has made the process cheaper and the prospect of individualized medicine more practical.

"All of a sudden we can see right before us the possibility of assessing each patient based on his or her genetic individuality," Valle said. "By the same token, there is an emerging field of exposure biology aimed at understating environmental-experience histories. We have the means to see the differences and similarities among all patients."

Valle said that JHIMP will help measure and interpret those differences.

"That is a big challenge, but one can certainly argue that the future of health care will be in individualized medicine," he said. "We have a strong clinical-rich tradition here at Johns Hopkins. We should be the leaders in this area. We should set the pace."

JHIMP's initial aim will be to select a small pilot group of patients, collect DNA samples from each, give each an environmental questionnaire, and begin to assess and develop a framework of utilizing genetic and environmental variants in each patient.

Researchers will develop a set of criteria of how and when to use such information. Valle said he realizes that major issues need to be confronted, such as building a secure computational infrastructure for storing and sharing this sensitive information.

"For it to be practical, the information needs to be instantly accessible so that a physician can use it following a diagnosis, but we need to store it in a way that protects the patient's privacy," he said. "The transformation from average medicine to individualized medicine will not happen overnight. It will be an evolving process."

Valle said that the program will initially target 10 biological systems and develop research tools to make use of the genetic information gathered from the pilot group. As part of this effort, the program will partner with the Johns Hopkins Center for Computational Genomics.

"Sarah's group will be crucial to our activities," Valle said.

To date, a 16-member JHIMP steering committee, from across JHU divisions, has been formed. Its principals include Kathy Hudson, director of the Genetics and Public Policy Center; Stephanie Reel, the university's chief information officer; and Alex Szalay, Alumni Centennial Professor in the Krieger School's Department of Physics and Astronomy.

"Alex is familiar with big-computations issues, so that is where he comes in. What we're doing also has enormous ethical aspects, and Kathy Hudson will play a vital role so that we can avoid pitfalls," he said.

Scott Zeger, acting provost and senior vice president for academic affairs, said that important scientific questions often require interdisciplinary teams for significant discovery.

"I am encouraged and pleased to see outstanding Johns Hopkins faculty, like these, working across disciplines, departments and schools to use the new biological measurements to advance our understanding of biologic processes and ultimately to promote health and treat disease," Zeger said.

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