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Meeting Explores Genetic Susceptibility to Cardiopulmonary Disease

By Eddy Ball
October 2008

Dennis Lang, Ph.D.
McAlister summarized the background of the workshop. (Photo courtesy of Steve McCaw)

After meeting with environmental cardiology grantees the previous day (see related story), Mastin chaired the workshop's key overview talks. (Photo courtesy of Steve McCaw)

Kleeberger began the subject-matter sessions by delivering the workshop charge. In the closing session, he also challenged participants to consider comparative genomics studies. (Photo courtesy of Steve McCaw)

Frank Gilliland, M.D., Ph.D.
University of Southern California Professor Frank Gilliland, M.D., Ph.D., smiled as he recalled some of the unexpected pitfalls in his work to develop a system-level approach to studying the effects of air pollution. (Photo courtesy of Steve McCaw)

London, left, and Rusyn were outspoken about animal models and computational needs during the final panel discussions of the meeting. (Photo courtesy of Steve McCaw)

Grace LeMasters, Ph.D.
University of Cincinnati Professor Grace LeMasters, Ph.D., above, was adamant about training investigators to look at "the big picture" of cardiopulmonary disease and "really reach across organs... [to] extend a system to other systems." (Photo courtesy of Steve McCaw)

George Leikauf, Ph.D.
University of Pittsburgh Visiting Professor George Leikauf, Ph.D., center, argued for fostering more trans-disciplinary training. "When we're training to be narrow," he said, "we attract people who think narrow." (Photo courtesy of Steve McCaw)

Wessling-Resnick pointed to the benefits of trans-disciplinary approaches. "What you really want to stimulate is growth that brings investigators together and creates new scientific endeavor," she said. (Photo courtesy of Steve McCaw)

Health Science Administrators from the NIEHS Division of Extramural Research and Training (DERT) joined their grantees, NIEHS intramural investigators and other experts in the fields of genetics and air pollution on September 4 and 5 for a meeting on genetic susceptibility to the health effects of air pollution exposure. Titled "Global Variability in Response to Air Pollution: Approaches to Translation of Cardiopulmonary Animal Disease Models," the meeting featured 12 thirty-minute talks and four panel sessions at the Sheraton Hotel in Chapel Hill, N.C.

As NIEHS Health Science Administrator Kimberly McAllister, Ph.D., explained in her opening remarks, the meeting was a follow-up to a one-day workshop held exactly a year earlier on September 4, 2007 in conjunction with the International Society of Environmental Epidemiology annual meeting in Mexico City.

"There was a real need," McAllister told the participants, "to have a workshop to bring together the mouse modelers and comparative biologists with the human geneticists and epidemiologists to try to stimulate translation.... We're hoping to foster collaboration among all of you and to think about better integration and interdisciplinary research in the field."

Meeting organizers divided the agenda into five parts, which moved sequentially from an overview of current understanding, through three sessions on investigational approaches, to an exploration in the final session of future needs and implementation. Each of the five sessions was chaired by a DERT staff member with related research and administrative interests - Acting Deputy Director Pat Mastin, Ph.D., Health Science Administrators McAllister, Sri Nadadur, Ph.D., and Kimberly Gray, Ph.D., and Susceptibility and Population Health Branch Chief Gwen Collman, Ph.D.

NIEHS Laboratory of Respiratory Biology Principal Investigator Steven Kleeberger, Ph.D., gave the first presentation of the Gene Susceptibility of Cardiopulmonary Diseases session with a talk on "Identification of Genetic Loci Associated with Pulmonary Effects in Animal and/or Human Studies" and also participated as a panelist for the session. Epidemiology Branch Principal Investigator Stephanie London, M.D., Dr.P.H., was a panelist for the Genetics to G x E (Gene and Environment) Interactions and Methods session and joined Biostatistics Branch Chief Clare Weinberg, Ph.D., on the Implementation session panel.

The presenters and panelists were a mix of bench scientists involved in human and animal studies, clinical researchers, biostatisticians and epidemiologists, and the meeting format encouraged a productive exchange of what were at times strongly opposed viewpoints about how best to blend current approaches into an integrated systems biology model. There was lively debate about the relative merits and limitations of candidate gene studies compared to unbiased genome-wide association studies, as well as discussion of the strengths and weaknesses of knockout and transgenic models of rodents.

Behind the differences of opinion, however, there was a celebration of diversity articulated by NIEHS grantee Ivan Rusyn, M.D., Ph.D., during his talk in the final investigational approach session. "I think it's wonderful that we're in one room talking together," he said as he proceeded to underscore the importance of bioinformatics in efforts to understand genetic interactions in the biological pathways of disease and the limitations of individual single nucleotide polymorphism (SNP) studies.

During the final panel session, discussion turned to ways NIEHS could encourage optimal collaboration of scientists from different disciplines with the remarks of Harvard School of Public Health Professor Marianne Wessling-Resnick, Ph.D. Wessling-Resnick is the current principal investigator for an NIH Roadmap Program in Interdisciplinary Training in Genetics and Complex Diseases, who feels strongly that such collaborations should lead to truly transformative scientific approaches. Modifying the review of training grants, she suggested, could motivate applicants to include truly cross-disciplinary components into their proposals.

To illustrate what she considers optimal collaboration, Wessling-Resnick compared the various terms used to describe cross-disciplinary approaches to children at play. As opposed to a multi-disciplinary approach of parallel research or an inter-disciplinary approach with shared tools, Wessling-Resnick described the most fruitful cross-disciplinary approach as trans-disciplinary - when investigators merge their tools in an effort to develop a genuinely new integrated approach.

Joel Schwartz, Ph.D.
An animated Joel Schwartz, Ph.D., principal investigator on NIEHS grants at Harvard University, weighed in on the computational challenges of trying to scan epigenetic modifications. (Photo courtesy of Steve McCaw)

Wrapping up the workshop, Collman summarized the needs expressed by grantees, most requiring additional funding. She thanked attendees for the input and quipped, "A workshop always ends on the money note." (Photo courtesy of Steve McCaw)

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