Creating the U-M Center for Arrhythmia Research: Interview with Jose Jalife, MD

Tell us about the creation of the U-M Center for Arrhythmia Research. How did this come about, and when did you get involved? The idea was conceived early last year after conversations I had with Dr. Hakan Oral, Chief of Clinical EP at U-M. We both agreed that it would be fantastic to join forces, work together in the same physical location and establish a unique translational research and training environment in cardiac EP; that is, an arrhythmia research center that would go all the way from the bench to the bedside. Subsequently I was invited by Dr. David Pinsky, Chief of Cardiovascular Medicine at U-M, to visit the campus and give a seminar about my research. Thereafter, the suggestion was made that I move to Ann Arbor with my group. I responded that we were a package deal a move could only happen if all members of our current Institute for Cardiovascular Research were recruited, including all of the faculty and their respective research groups (altogether about 33 investigators). An offer was made that was too attractive to ignore. As such, what appeared first as an impossibility turned into a groundbreaking and far-reaching reality. What were your reasons for wanting to move to U-M? There are many scientific and professional reasons for wanting to move to such an excellent university. First and foremost, the idea of collaborating directly with Drs. Oral and Fred Morady, two outstanding clinical electrophysiologists, is extremely attractive. For example, one of our major objectives is to investigate the mechanisms of atrial fibrillation (AF), which is the most common cardiac arrhythmia seen in clinical practice and the major cause of stroke. Being close to a first-class clinical EP lab such as the Hakan-Morady lab gives us basic scientists the unique opportunity to team up with world-leading experts in our efforts to test directly and ethically in patients the relevance of the ideas for AF diagnosis and therapy that we generate in the experimental laboratory. Conversely, many puzzling clinical questions about AF can be addressed in the experimental lab and the predictions derived from the experiment can in turn be tested back in the clinical EP lab. In other words, combining the two teams to target the molecular, genetic and cellular causes of AF, as well as focus on patients with that condition, will empower us to move the field forward in leaps and bounds. Another reason is that the scientific environment at the University of Michigan is truly exceptional. While our primary appointments will be in the Division of Cardiology of the Department of Internal Medicine, most of us have been offered or will seek joint appointments in basic science departments such as Pharmacology and Molecular & Integrative Physiology. This will provide us with a great opportunity to establish new collaborations with outstanding basic scientists in those departments whose interests and expertise compliment ours. Moreover, access to those departments will enable us to recruit additional highly trained and motivated graduate students to work in our respective laboratories. Finally, the facilities and resources available for U-M researchers are among the most modern and complete, and the research support personnel is among the best trained in the world. How many staff members from SUNY will move to the U-M Center for Arrhythmia Research? Who are some of the staff members that will be coming with you? Altogether, a total of 33 individuals will be moving to Ann Arbor as part of our team. Mario Delmar, MD, PhD and I have been appointed as professors with tenure and co-directors of the center. The appointments of Omer Berenfeld, PhD, Karen Vikstrom, PhD, Jerome Kalifa, PhD, and Justus Anumonwo, PhD, are as tenure track assistant professors. In addition, five non-tenure track assistant professors, Drs. Karen Maass, Sandeep Pandit, Sergey Mironov, Hassan Musa and Sharon Zlochiver will be joining us, as well as a number of postdoctoral fellows, graduate students, technicians and clerical staff. Incidentally, three of our students, Katherine Campbell, Luqia Hou and Halina Chkourko have been accepted as full-time students in the M&IP Department, while the rest will remain as SUNY students while working with us in Michigan. When will the move be complete? When will the U-M Center for Arrhythmia Research officially open? The move will start around March 15, 2008; I hope to complete it before April 1. There is no official date yet. Renovations of the space are currently undergoing. Will the U-M Center for Arrhythmia Research be located in an existing building, or are there plans to build a new facility? Initially, the Center for Arrhythmia Research will be in an existing building that has been leased by U-M at a location in Ann Arbor, about 6 miles from the main campus. The reason for this was that on such a short notice it was virtually impossible to find adequate consolidated research and office space on campus for 33 people. The Dean of the Medical School has assigned for us prime space in a research building that is currently under construction very close to the Medical Center. We are scheduled to move to that location in about two years time. What new and/or ongoing research will you be bringing with you or working on at U-M? I can summarize our current work in two major areas of cardiac electrophysiology research. The first one deals with the problems of intercellular communication and impulse propagation in the heart. The second one investigates arrhythmia mechanisms in two rare but lethal inherited cardiac diseases. In the first area, the clearly defined central theme of intercellular communication and impulse propagation unifies four highly interactive projects that comprise one of our two NIH program project grants. The propagation of electrical impulses through the heart depends on both functional ion channels controlling the excitation of the cardiac cell and intercellular communication through open channels formed by proteins called connexins on the membranes of those cells. Cardiac dysfunction and arrhythmias are direct results of the lack of intercellular communication or altered excitation. As such, each of the projects contributes crucial information on one or more aspects to that central theme and provides compelling scientific rationale for conducting multidisciplinary research. Project 1 will study mechanisms of AF in the human heart. It, in fact, represents the culmination of many years of experience and hard experimental work leading to a better understanding of cardiac fibrillation using both mathematical and experimental animal models. For the first time, we feel confident that knowledge derived from such work can be applied in a rigorous manner to the understanding of the most common arrhythmia seen in clinical practice in human patients, i.e., atrial fibrillation. This would not be possible without the direct integration of project 1 with project 2, which addresses mechanisms of cardiac fibrillation at the molecular level, or without the daily communication between the investigators and the sharing of expertise and resources that are vital to both projects. Project 3 addresses the structural bases for the regulation of cardiac intercellular communication under physiological or pathological conditions. Closure (or not) of the intercellular channels formed by the connexin proteins in the whole heart is considered a fundamental aspect of impulse propagation. In this regard, projects 2 and 3 are by necessity highly interactive both at the experimental and theoretical levels and provide crucial thematic continuity to the program. Whereas through the years, the laboratory of Dr. Mario Delmer, Co-director of the Center for Arrhythmia Research, has developed tremendous expertise in cellular physiology, it lacks the necessary resources for the study of propagation in multicellular preparations, particularly by means of optical mapping. My laboratory, on the other hand, has well-recognized expertise and state-of-the-art equipment to conduct research in that area. Project 4 is aimed at developing small proteins that can modify intercellular communication and thus, these proteins may be potentially used to manipulate impulse propagation by means of affecting the connexin proteins. Projects 3 and 4 both deal with the issue of regulation of intercellular communication through the analysis of the relation between structure and function of the connexin proteins. In project 3, we manipulate the connexin structure by genetic means. In project 4, the function of the protein structure is affected by small proteins that we clone in the laboratory. It is hard to generate two separate projects that are so closely related without falling into overlap. The area of our second NIH program project involves multidisciplinary research into the manner in which two very rare but extremely dangerous inherited diseases, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), may lead to sudden cardiac death in affected individuals. Here our general objective is to determine how alterations of proteins that control the cellular structure or the movements of calcium ions inside and outside of the cardiac cell translate into electrical abnormalities that ultimately result in life-threatening arrhythmias and death. We conduct experiments and computer simulations to compare and contrast basic cellular and biophysical alterations underlying the possible mechanisms that lead to cardiac rhythm disturbances in patients suffering from these devastating diseases. Thus, our research programs address important scientific topics of direct clinical relevance. They are helping us answer questions that are germane to arrhythmia mechanisms in well-known cardiac disorders such as heart failure and ischemic heart disease, as well as more rare conditions such as ARVC and CPVT. How has word of the new U-M Center for Arrhythmia Research been received by existing EP staff at U-M? Will you be working together on research projects? So far, the response has been fabulous. Everyone has been welcoming and very supportive, offering help with our move. Moreover, we have already established collaborations with investigators within the Department of Internal Medicine as well as other departments including Molecular & Integrative Physiology and Pharmacology. How will the U-M Center for Arrhythmia Research be unique from other arrhythmia research programs? What are some of the ways this collaboration between U-M and the Center for Arrhythmia Research will help benefit patients? The Center for Arrhythmia Research allows the unique opportunity of bringing together a group of investigators and experts in various relevant fields, including cardiology, structural and molecular biology, molecular genetics, cellular electrophysiology, biophysics, biomedical engineering, and mathematics, to conduct cooperative research projects. Our relocation to Ann Arbor will enable us to significantly expand the scope of our research through our new collaboration with U-M researchers. Together, we should be able to apply knowledge derived from many years of experience investigating the cellular and molecular bases of cardiac electrical activity, from both theoretical and experimental points of view. Is there anything else you d like to add? Thank you for your interest. We are all extremely excited about this new venture. For more information, please visit: www.umcvc.org