As advances in research tools yield more complex questions, research becomes more collaborative. Investigations today require the perspectives of researchers from molecular biology to genetics to computer modeling and imaging, whether they are in different departments at a single university, or across the country at multiple institutions.
This is especially true for basic research into heart disease, says Donald M. Bers, who holds the Silva Chair for Cardiovascular Research and is chair of UC Davis School of Medicine’s Department of Pharmacology.
Research studies used to be conducted institution by institution. Now, Bers says, "The National Institutes of Health encourages collaboration among departments and institutions so that the very best people are looking at the same problem and talking with each other about what they see."
"The National Institutes of Health encourages collaboration among departments and institutions so that the very best people are looking at the same problem and talking with each other about what they see."
To that end, Bers and UC Davis have established a highly collaborative, multidisciplinary research core where clinical and basic scientists, under the same umbrella, can tackle existing challenges in the prevention and treatment of heart failure and cardiac arrhythmias.
Over the past decade, the cardiovascular scientific community at UC Davis has experienced striking growth, with the expansion of existing research programs and the development of new ones.
The cardiovascular research core faculty has increased as well – by a third since 2007 – and represents five colleges at UC Davis – School of Medicine, School of Veterinary Medicine, College of Engineering, College of Biological Sciences and College of Agricultural and Environmental Sciences – and nine departments ranging from pharmacology to molecular bio-science to medicine to entomology. One geographic center of the cardiovascular research faculty that facilitates interaction is in the recently opened Genome and Biomedical Sciences Facility.
The recent addition of a cardiovascular nursing expert expands UC Davis’ multidisciplinary research in this field. Holli DeVon, a nationally recognized expert in cardiovascular nursing research, recently joined the Betty Irene Moore School of Nursing founding faculty team. She’s leading a $1.9 million National Institutes of Health study in partnership with UC Davis Medical Center Emergency Department to determine the influence of gender on symptom characteristics during acute coronary syndromes. (See related story)
Bers this year received a key NIH stimulus grant to round out the cardiovascular team, which will open up new avenues of multidisciplinary collaborative grants, such as prestigious NIH program project grants that would synergize with existing faculty. From that grant is the team’s newest member, Crystal M. Ripplinger, whose lab combines multiple imaging modalities across multiple spatial scales to determine factors contributing to cardiac arrhythmias.
She joins faculty researchers led by Bers that participate on four focus teams:
- The ion transport and cardiovascular function team that includes Bers; Nipavan Chiamvimonvat, the Roger Tatarian Endowed Professor of Cardiovascular Medicine in the Division of Cardiovascular Medicine; Peter Cala, professor and chair in the Department of Physiology and Membrane Biology; Ye Chen-Izu, assistant professor in the departments of Biomedical Engineering, Cardiovascular Medicine and Pharmacology; Yu-Fung Lin, assistant professor, and Jie Zheng, associate professor, both in Physiology and Membrane Biology; and Heike Wulff, associate professor, Colleen Clancy, associate professor, Johannes Hell, professor, and Sanda Despa, assistant professor, all in Pharmacology.
- The excitation-contraction coupling group that includes Isaac Pessah, professor and chair of Molecular Biosciences in the School of Veterinary Medicine and director of the National Institute for Environmental Health Sciences Center for Children's Environmental Health; Leighton T. Izu, associate professor in Pharmacology; Sue Bodine, professor in Neurobiology, Physiology and Behavior in the College of Biological Sciences, and in Physiology and Membrane Biology; and Aldrin Gomes, assistant professor, and Samantha Harris, assistant professor, both in Neurobiology, Physiology and Behavior and in Physiology and Membrane Biology.
- The translational cardiovascular team that includes Chiamvimonvat; Bers; Wulff; Chen-Izu; Anne A. Knowlton, professor in Pharmacology; Mark D. Kittleson, professor in the Department of Medicine and Epidemiology in the School of Veterinary Medicine; and veterinarian Julie Bossuyt, assistant professor in Pharmacology.
- The vascular/endothelial membrane interaction group that includes Knowlton; Fitz-Roy Curry, professor of Physiology and Membrane Biology; Bruce Hammock, distinguished professor of Entomology and Cancer Research Center and director of the National Institute of Environmental Health Sciences – UC Davis Superfund Basic Research Program; and Scott I. Simon, professor, and J. Kent Leach, assistant professor, both in Biomedical Engineering.
This span of expertise both advances UC Davis’ long tradition of interdisciplinary collaboration and further establishes the health system’s reputation as a leader in cardiovascular research partnership.
The collaborative style will greatly speed scientific progress into heart disease because it allows a question to be pursued from various directions at the same time, and findings to be checked against other work.
For instance, Bers leads a $12 million study with Joan Heller Brown, chair of the Department of Pharmacology at UC San Diego, and other colleagues around the country. They are studying a protein known as calmodulin-dependent protein kinase, which has become a new target for a drug being developed for heart failure and arrhythmias.
"We are studying a protein known as calmodulin-dependent protein kinase, which has become a new target for drug being developed for heart failure and arrhythmias. It may turn out in the long run to be as important a target as beta-blockers are in the treatment of heart failure."
"Our work has triggered the interest of pharmaceutical companies," Bers says. "It may turn out in the long run to be as important a target as beta-blockers are in the treatment of heart failure."
Bers is seeking funding for collaboration with two groups at Vanderbilt University in Nashville to study arrhythmias. The pending program project grant application includes four synergistic collaborative projects – two projects are led by Bers and Isaac Pessah, a professor in the Department of Molecular Biosciences at UC Davis’ School of Veterinary Medicine, and two projects are led by two faculty members at Vanderbilt.
He says the research team may have discovered a new and previously unknown mechanism that may lead to cardiac arrhythmias in heart failure and in patients suffering from ischemic (reduced blood flow) heart disease.
New drug targets
Bers is one of the world’s experts in calcium channels in the heart. The correct opening and closing of these calcium channels are essential for the heart muscle to contract and pump blood around the body. However, when these calcium channels open at the wrong time, a life-threatening arrhythmia can be triggered. Arrhythmia is one of the main causes of death in people with heart failure.
The UC Davis-Vanderbilt grant proposal would allow the research team to thoroughly examine the importance of the pathway that involves the inappropriate opening of these critical calcium channels, and to develop novel drugs to combat this pathway.
The work could lead to other new targets for drug treatment in heart failure.
While at Loyola University in Chicago, Bers worked with the heart transplant surgeons there to study what really goes wrong in living human heart cells. To engage in similar research in California, Bers has partnered with colleagues in cardiology at UC San Francisco in the heart transplant program (which transplants up to 30 hearts a year) and organ donor network. The UCSF-UC Davis team is using valuable still-living human heart tissue to better understand the fundamental nature of human heart disease.
This research is supported by an NIH challenge grant as part of the American Recovery and Reinvestment Act of 2009, of which only about 200 were funded from among 22,000 applications across the nation.
Athletes’ heart disease
"I think UC Davis is primed for this new world of research because we already collaborate. People are open to sharing across the fields because they understand the benefits of working together to share resources."
Bers’ colleague from Neurobiology, Physiology and Behavior, Samantha Harris studies the proteins in heart cells that cause them to contract, and she is interested in a disease condition known as familial hypertrophic cardiomyopathy. Familial hypertrophic cardiomyopathy is a leading cause of sudden death in young people and athletes. It is most often caused by a genetic defect in a contractile protein in heart cells. While knowledge is increasing about how these human mutations alter contraction of the heart, how these changes cause cardiac arrhythmias is still unknown.
Maine coon cats have a form of familial hypertrophic cardiomyopathy similar to that in humans. And it happens that UC Davis has the only colony in the world of cats with the condition. Mark Kittleson, a professor in the School of Veterinary Medicine, began putting the colony together in the late 1990s.
Harris was recently awarded a two-year grant from the NIH to work with Kittleson, using his cats as a model of the human disease. Part of the grant will be shared with Cincinnati Zoo’s Bill Swanson, who is a cat-breeding expert. Another collaborator, Pradeep Luther, works from Imperial College in London. By gathering partners, the team will be able to study and maximally utilize their resources.
"I think UC Davis is primed for this new world of research because we already collaborate," Harris says. "People are open to sharing across the fields because they understand the benefits of working together to share resources."
"The bottom line is we can really test our conceptual models, and what we think we have learned from animal models, and see if it really happens in people," Bers says.
The need is significant. More than 81 million Americans over age 20 have one or more types of cardiovascular disease such as high blood pressure, coronary heart disease or congestive heart failure. Peripheral vascular disease is estimated to affect up to 10 million Americans. UC Davis Health System is improving cardiovascular health through state-of-the-art patient care, cutting-edge research, education and outreach.