Genomics of Cardiomyopathies
Functional studies of mutant cardiomyopathy genes are also performed to evaluate the consequences of the defective proteins on cellular models. We are using cardiac cellular model and zebrafish model organisms to recapitulate the mutant phenotype, following gene discovery in our genetic studies. Zebrafish studies are done in collaboration with Dr. Debbie Garrity at Colorado State University.
We are currently exploring applications of nanobiotechnology and bioengineering to the study of heart function and treatment of heart failure and cardiomyopathies. With the use of atomic force microscopy (AFM), in collaboration with scientists at the University of Trieste (Italy), we have discovered biomechanical changes at the nanoscale in cardiac cells carrying genetic mutations (lamin A/C gene). In addition, using nanobiotechnology, biophysics, cell biology and bioengineering, with a multidisciplinary approach in collaboration with our UCD Department of Bioengineering and nanoscientists at the University of Trieste (Italy), we are developing ‘next-generation’ smartbiomaterials for tissue engineering and cardiac repair.
Brisa Pena Castellanos
PhD Graduate Student
Mary Sweet, HMGP Graduate student
MS Graduate Student
Rene Begay, BS
Visiting Cardiology Fellows
Sharon Graw, PhD. CGC, Study coordinator
Dobromir Slavov, PhD, Laboratory manager
Valentina Martinelli, PhD
Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.
The Cardiomyopathy Lamin A/C D192G Mutation Disrupts Whole-Cell Biomechanics in Cardiomyocytes as Measured by Atomic Force Microscopy Loading-Unloading Curve Analysis.
AFM single-cell force spectroscopy links altered nuclear and cytoskeletal mechanics to defective cell adhesion in cardiac myocytes with a nuclear lamin mutation.
Analysis of long- and short-range contribution to adhesion work in cardiac fibroblasts: an atomic force microscopy study.
We are part of the NIH funded North American Arrythmogenic Right Ventricular Dysplasia/Cardiomyopathy Registry, in collaboration with Dr. Frank Marcus (University of Arizona), Dr. Jeff Towbin (Cincinnati Children Hospital/University of Tennessee), Dr. Jeff Saffitz (Harvard medical School) and Wojchiech Zareba (University of Rochester).
Our laboratory is funded by the NIH/NHLBI, NIH/NCATS Colorado CTSA, Fondation Leducq TNE, European Research Council, American Heart Association, John Patrick Albright Foundation.
We are part of pilot trials to treat cardiomyopathies, such as the VANISH trial (HCM) and the Array-797 trial (DCM).
Our laboratory is based on the collaboration between Co-Directors Dr. Mestroni and Dr. Taylor, who share the lead of the Molecular Genetics laboratory and the Adult Medical Genetic Program. We also collaborate with a network of local and international investigators, in particular investigators at the University of Trieste and Florence in Italy under the auspices of two bilateral agreements, the University of Arizona, the University of Heidelberg. Recently, our laboratory has been awarded by the prestigious Fondation Leducq Transatlantic Network of Excellence, where we investigate the origin and treatment of arrhythmogenic cardiomyopathy in collaboration with Dr. William McKenna, University of London, Dr. AJ Marian, University of Texas Houston, Dr. Thomas Weber, Mount Sinai SOM NY, Dr. Orfeo Sbaizero, University of Trieste and Dr. Hans Clevers, Hubrech Institute (The Netherlands).