American Heart Association Fellowship

Dr. Eckhardt takes her interest in inherited arrhythmias from the clinic, where she sees patients, to the laboratory where she studies mutations in on channels that cause Long QT syndrome, Brugada syndrome, Catacholiminergic polymorphic ventricular tachycardia, Short QT syndrome and familial atrial fibrillation. The gene -KCNJ2- encodes KIR2.1, the pore-forming α-subunit of the inwardly rectifying potassium current (I_K1) in the heart. Dr. Eckhardt is particularly interested in the biophysical properties of Kir2.1 and other potassium channels that underlie arrhythmia mechanisms. Some of these properties relate not to the ion channel itself, but ion channel-associated proteins such as the major scaffolding protein caveolin-3 (Cav3). Extensive studies indicate that Cav3 and Kir2 associate in ventricular myocytes and mutations in CAV3 affect the normal functioning of wild type Kir2.1 and Kir2.2. The current focus is on the specific nature of these interactions and how they relate to the underlying arrhythmia mechanisms for the I_K1 macromolecular complex.

The long-term goal of Dr. Kamp’s research is to advance the treatment of cardiac diseases using novel therapies directed at cardiac arrhythmias and by optimizing strategies to regenerate myocardium. Briefly, his laboratory studies the role of ion channels in normal cardiac physiology and pathophysiology using a variety of approaches including cellular electrophysiology, biochemistry, pharmacology, and molecular imaging. A unique aspect of Dr. Kamp’s work is the use of human pluripotent stem cell-derived cardiomyocytes. By inducing patients’ cells to pluripotent stem cells, postdoctoral fellows and students in Kamp’s lab create cardiomyocytes that express the clinically relevant pattern of ion channel proteins found in the human heart. Additional studies explore cell-based therapies for myocardial regeneration in cardiac disease models using cardiovascular progenitor cells. Dr. Kamp has made major contribution to the field of cardiac generation by expanding a library of reprogramming factors to generate induced cardiac progenitor cells (iCPCs) from human fibroblasts as well as devising methods to promote iCPCs differentiation and expansion.

Dr. Liu examines the regulatory mechanisms underlying normal functions of smooth muscle cells and how these mechanisms become de-regulated in vascular disease. One major focus is on cell death. The conventional view is that apoptosis contributes to vascular pathogenesis of aneurysmal disease by reducing the number of muscle cells which are a major source of extracellular matrix proteins. Data from the Liu lab indicate a previously unreported role for apoptosis, i.e. amplification of the pro-inflammatory signal. They showed that apoptotic smooth muscle cells secret chemokines such as monocyte chemoattractant protein-1 (MCP-1) which are critical for vascular inflammation. More recently, Dr. Liu and her lab have demonstrated that necroptosis, a novel cell death pathway, is an integral component of aneurysm disease progression. They identified several new inhibitors to necroptosis. Data generated from several preclinical models demonstrate the therapeutic potential of these inhibitors in preventing aneurysm rupture and minimizing neurological damage associated with strong. Students who work in Dr. Liu’s lab will have exposures to interdisciplinary studies ranging from basic discoveries to therapeutic development.

Dr. Masters researches the design of engineered environments to study tissue repair and disease mechanisms. Traditional tissue engineering techniques focus primarily on the construction of healthy neo-tissues, wherein optimization of the biomaterial system is performed to promote maintenance of a healthy cell phenotype. However, an emerging application of tissue engineering is the recreation or replication of diseased human tissues, which will uncover disease mechanisms and etiology and also provide advanced, physiologically-relevant in vitro platforms for testing disease treatments. To this end, engineered in vitro tissue systems are developed to mimic elements of in vivo dysfunction of various tissues, including heart valves and heart muscle. For example, work creating calcific valvular disease in vitro has revealed information about the roles of extracellular matrix components, growth factors, peptide-receptor interactions, and intracellular signaling pathways in valve calcification. Research in heart valves and heart muscle concentrates on ways to tailor both 2-D and 3-D in vitro environments to regulate cell phenotype of these cells and create defined systems that mimic elements of native pathologies, thereby providing insight into the mechanisms of disease progression and potential targets for its prevention.

Dr. Robertson is a Professor in the Department of Neuroscience and is also an active member of the UW Stem Cell and Regenerative Medicine Center. As a graduate student at Washington University she studied mechanisms underlying the spinal control of limb movement. She and a colleague cloned Drosophila slowpoke, the first gene encoding a Ca-activated potassium (BK) channel. She made the first recordings from channels encoded by the EAG gene and, as a beginning assistant professor in the Physiology Department at UW-Madison, established that the hERG gene encoded the channels underlying the repolarizing cardiac current I_Kr. She and her colleagues translated these findings into drug safety technology used worldwide to reduce the risk that drugs in development cause sudden cardiac death. Her more recent work utilizes cardiomyocytes derived from human induced pluripotent stem cells as a model system for studies of human cardiac repolarization.