Beckman Symposium 2012 - Diseases of Molecular Motors and Cytoskeleton

Euan Ashley is an Assistant Professor of Medicine (Cardiovascular) at the Stanford University School of Medicine and is director of the Stanford Center for Inherited Cardiovascular Disease, the Stanford Hypertrophic Cardiomyopathy Center, and the Stanford Cardiopulmonary Exercise Testing Laboratory. His laboratory is focused on understanding the molecular genetics of myocardial adaptation, the process by which the heart adapts to exercise or disease stress. The lab uses an integrated systems approach using genomic analysis to identify gene expression networks and bench tools to define causality in the biology of key genes and signaling systems. The lab also studies inherited cardiovascular diseases including cardiomyopathy and inherited arrhythmia syndromes and the apelin-APJ signaling system’s connection to heart failure and cardiovascular disease.

Robert Goldman is the Stephen W. Ranson Professor and Chair of the Department of Cell and Molecular Biology at the Feinberg School of Medicine of Northwestern University. His laboratory’s research focus is on the structure and function of cytoskeletal systems, particularly the intermediate filament (IF) system in fibroblasts, epithelial cells, and nerve cells. Using a variety of techniques, the lab has demonstrated that IFs form elaborates networks that course throughout the cytoplasm and establish connections with both the nuclear and cell surfaces. The lab is developing models to study the mechanisms involved in IF alterations in various diseases, including amyotrophic lateral sclerosis (ALS). They have been able to induce neurofibrillary tangles to form in single cultured nerve cells. These tangles are similar to those found in ALS neurons and therefore, the lab has been able to study the effects of neurofilament tangle formation in a single cell.

Lawrence Goldstein is a Howard Hughes Medical Institute Investigator and Professor of Cellular and Molecular Medicine and Neurosciences at the University of California, San Diego. The primary goal of his laboratory is to unravel the way in which molecular motors interact with and control the behavior of axonal vesicles, and to relate this understanding to the molecular basis of neuronal defects in Alzheimer’s Disease (AD) and Niemann Pick Type C disease. The laboratory uses pluripotent stem cell lines that contain known mutations that cause hereditary AD, as well as a series of embryonic stem cell lines in which expression of the gene that causes Niemann Pick Type C disease is reduced as in true human disease. They use these stem cell lines and animal models to probe basic mechanisms of vesicle movement and sorting in neurons, and how such mechanisms inter-relate with disease development.

Leslie Leinwand is a Professor of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder. Her laboratory is interested in understanding how the genetic landscape of the mammalian heart shifts during feeding, exercise, pregnancy, and disease. One of the diseases the group focuses on is hypertrophic cardiomyopathy, which is the leading cause of sudden death in young athletes. To understand the pathogenesis of the disease, the lab has used approaches ranging from biophysical analysis of mutant proteins to analysis in genetically manipulated mice. One novel approach has been the use of the Burmese python as a study organism. The python’s heart and liver experience rapid hypertrophy on ingestion of a meal, a hypertrophy similar to the beneficial heart enlargement experienced by trained athletes. Genetic analysis of this type of adaptive response may lead to the development of therapeutic treatments that promote the beneficial growth of heart cells.