Cardiovascular Muscle and Organ Research Overview - Molecular Pathology

Research Overview - Cardiovascular Muscle and Organ

HEART: CONGENITAL HEART DISEASE, CARDIOMYOPATHY, ISCHEMIA, AGING. Dr. Rolf Bodmer has utilized the power of Drosophila genetics to delineate detailed genetic pathways underlying heart development, which have been found to be conserved in vertebrates. Recently, he has developed Drosophila as a model to define genetic pathways involved in aging, with a focus on the physiological decline of heart function with age. Dr. Ken Chien was a pioneer in developing the mouse as a model system for human cardiac disease. His lab has uncovered genetic pathways involved in cardiomyopathy and arrhythmias. A current focus of the Chien lab is on a novel population of progenitor cells found in adult heart in rodents and in man which can differentiate into cardiomyocytes. Dr. Ju Chen is a human geneticist who has created many state of the art mouse models to facilitate tissue specific knockout of target genes. Research in the Chen lab is focussed on interactions between muscle cells and connective tissues in both heart and skeletal muscle, utilizing mice with mutations affecting these interactions. Dr. Sylvia Evans is exploring heart development. cardiac lineage determination, and congenital heart disease, utilizing mouse as a model system. The Evans lab is studying two potential progenitor/stem cell populations, one which gives rise to cardiomyocytes, and another which gives rise to cells of the coronary vasculature and fibroblasts in the heart. Dr. Roberta Gottlieb is exploring molecular pathways in ischemic heart disease and programmed cell death pathways which may contribute to heart failure in the setting of ischemia. Dr. Gottlieb utilizes isolated rat or mouse heart preparations and a novel peptide delivery system to explore cardiac responses to hypoxia and pathways to protect against cell death. Dr. Paul Insel utilizes primary cultures of rodent cardiomyocytes to study signalling mediated by G-protein coupled receptors, which has been shown to be involved in the development of cardiac hypertrophy. The Insel lab has discovered that signalling pathways may be determined by grouping of signalling proteins within lipid rafts in cardiomyocytes. Recently, the Insel lab has begun to investigate the cross talk between cardiac fibroblasts and cardiac myocytes, in cell culture studies. Dr. Mark Mercola discovers molecules and genes for cardiomyocyte regeneration from embryonic stem (ES) cells. The lab uses frog, chick, and mouse embryos to characterize genetic pathways that induce and pattern the heart. A new and important part of his research is a collaborative effort of chemists and instrumentation experts to run high throughput, robotic screens of large chemical libraries for small molecule inducers of ES cell cardiogenesis. Dr. Xiang-Dong Fu is exploring tissue-specific regulation of gene expression by alternative splicing, utilizing mouse as a model system. Recent studies in the Fu lab have demonstrated that malfunctions of the splicing apparatus can result in cardiomyopathy, and have defined specific genes whose aberrant splicing contributes to disease. Dr. Fu is interested in further defining the role of aberrant splicing in human disease.

SKELETAL MUSCLE: MYOPATHIES, NEUROMUSCULAR DISORDERS, ALZHEIMER'S. Dr. Ju Chen is defining novel genetic pathways affecting skeletal muscle development and function, and has uncovered genetic mutations which cause muscular dystrophy in mouse and man. The Chen lab is working toward understanding the manner in which these mutations cause disease. Dr. Eva Engvall is interested in the role of cell adhesion in myogenesis and muscular dystrophy, and has utilized cat, dog, and mouse models of myopathies in her research. One of the goals of the Engvall lab is to develop therapeutic reagents which can ameliorate these diseases, with an emphasis on interactions between the muscle cytoskeleton and the extracellular matrix. Dr. Hudson Freeze is a leader in discovering human genetic disorders in protein glycosylation which result in defects in multiple organ systems including neurologic, hepatic, and gastrointestinal. Dr. Paul Martin is investigating several underlying causes of neuromuscular disorders, including muscular dystrophies and Alzheimer's disease. The Martin lab uses the mouse as a model system, and is focussed on synaptogenesis, glycosylation, and inclusion body myopathies. Dr. Diane Shelton investigates the cause of muscular dystrophy in cat and dog models with an emphasis on histochemical pathology. Work from the Shelton lab has led to the discovery of distinct genetic causes underlying both inherited and sporadic dystrophies.

VASCULATURE AND IMMUNE SYSTEM: ATHEROSCLEROSIS. Dr. Sylvia Evans is studying coronary vessel formation in mouse, defining vasculogenic pathways that may be unique to the heart and important for designing therapies directed at coronary vessel disease. Dr. Chris Glass is one of the leaders in defining molecular pathways which underlie the contribution of macrophages to atherosclerosis. The Glass lab utilizes mouse models and bioinformatics to uncover transcriptional networks underlying vascular disease. The Glass lab also studies myeloid differentiation and leukemia. Dr. Paul Insel is interested in the role of G protein coupled receptors in vascular smooth muscle regulation, utilizing cell culture systems to define critical rate limiting components of these signalling pathways.

KIDNEY: RENAL DISEASE IN DIABETES, INFLAMMATION, HYPERTENSION. Dr. Roland Blantz investigates physiological and pathophysiological pathways underlying kidney function and disease, utilizing in vivo physiological approaches in rat models, complemented by in vitro biochemical assays. Pathways of particular interest include those involved with NO production and signalling. Studies also examine the specific mechanisms of diabetic kidney growth and hyperfiltration. Arginine metabolites are critical to the inflammatory response and the regulation of cell proliferation, and these metabolic pathways are highly regulated temporally.

PANCREAS: DIABETES. Dr. Fred Levine is delineating genetic pathways underlying pancreatic beta cell development toward developing therapies for diabetes. Dr. Levine has developed and studied a human pancreatic beta cell line to utilize as a model for beta cell development and targeted therapies. His lab is working on pancreatic stem cell systems for the treatment of diabetes.

COLON: COLITIS, CROHN'S DISEASE. Dr. Hudson Freeze is defining the manner in which glycosylation contributes to inflammatory bowel disease, both colitis and Crohn's disease. He also investigates the cellular and molecular basis of protein-losing entropthy, which often arises following heart surgery to correct univentricular defects. Dr. Martin Kagnoff focuses on the molecular biology of interactions between bacteria and the gut epithelium, which are involved in diseases of the intestine, such as inflammatory bowel disease and celiac disease.

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