Congenital Heart Disease (CHD) is the most common major birth defect, affecting an estimated 1 in 130 live births, yet the cause remains elusive. In a growing number of cases, genetic studies have traced CHD to defects in cilia, hair-like structures that are found in the developing heart. The Yuan lab seeks to understand how these cilia act as antennae to sense and translate extracellular signals into molecular processes that sculpt the early heart. A deeper understanding of how cilia function in heart development will provide critical insight into the rational design of new diagnostics and therapeutics that have the potential to improve the outcome and care of patients with CHD.
The Yuan lab utilizes embryological, cellular, genetic, molecular, biophysical, and microscopy-based approaches in zebrafish, mice and cell-based models. In addition, the Yuan lab develops and applies cutting-edge optical approaches, namely light sheet microscopy, optical tweezers, optogenetics, optical nanomaterials and laser nanosurgery.
Dr. Shiaulou Yuan is an Assistant Professor of Medicine at Massachusetts General Hospital and Harvard Medical School. Dr. Yuan received his undergraduate degree in molecular cell biology from University of California, Berkeley in 2004 under Dr. Athanasios Theologis. He completed his Ph.D. in genetics from Yale University in 2011 with Dr. Zhaoxia Sun. Dr. Yuan performed his postdoctoral training in cardiovascular biology and developmental biology with Dr. Martina Brueckner at Yale School of Medicine. He received additional postdoctoral training in light sheet microscopy, laser nanosurgery techniques, and biophysical approaches with Dr. Joe Howard at Yale University and Dr. Scott Fraser at University of Southern California. In 2018, he started his own independent laboratory in the Cardiovascular Research Center at Massachusetts General Hospital and Harvard Medical School. Dr. Yuan’s research focuses on elucidating the cellular and molecular mechanisms that shape the developing heart, and in particular, the function of cilia in this process.
Director, Program in Cardiovascular Imaging, Martinos Center for Biomedical Imaging,
Director, Cardiovascular Bioengineering and Biomedical Imaging (CABBI) Program,
Medical Director, Institute for Innovation in Imaging (I3),
Cardiology Division and Department of Radiology, Massachusetts General Hospital;
Affiliated Faculty, Health Science and Technology (HST) Program,
Massachusetts Institute of Technology and Harvard Medical School
The Sosnovik lab is highly multidisciplinary with efforts in basic science, bioengineering and biomedical imaging all aimed at improving the understanding of common cardiovascular diseases. The lab has a strong interest in mechanisms of cardiomyocyte injury and death including apoptosis, free DNA release and autophagy. This has been coupled with an interest in developing technologies to guide myocardial regeneration and the imaging of the cellular architecture of the heart to elucidate, and mimic, its microstructural properties. Fundamental discovery in cardiomyocyte biology is combined with fundamental discovery in bioengineering and biomedical imaging. This includes the development of targeted and theranostic nanoparticles, capable of detecting and modulating processes such as apoptosis and inflammation. Developments/applications in biomedical imaging have included initial descriptions of fluorescence tomography, diffusion tensor MRI tractography, optical coherence tractography, fluorescence lifetime imaging and targeted molecular MRI in the heart. New focus areas in the lab include PET-MR of histone deacetylase (HDAC) expression in the heart and mechanisms to reverse myocardial fibrosis. Systems approaches are used to model and integrate interconnected processes such as autophagy, HDAC expression and fibrosis. Our work ranges from single cells, including IPSc-derived cardiomyocytes, through small and large animal models to translational studies in humans.
Millions of patients die annually from diseases that affect organs with limited regenerative capacity such as the heart. In contrast, zebrafish regenerate most organs naturally after injury. The goal of our research is to identify barriers to heart regeneration using the zebrafish as a model organism. Our lab is particularly interested in understanding how polyploidization (the increase in DNA content associated with the maturation of certain cell types) reduces the regenerative competence of cardiomyocytes. Our ultimate goal is to make fundamental discoveries that could be later used to design strategies to regenerate the human heart after myocardial infarction.
Dr. Gonzalez-Rosa received his Ph.D. in Molecular Biology from the Universidad Autonoma (Madrid) and the Spanish National Center for Cardiovascular Research in 2013. During his thesis work under the supervision of Dr. Nadia Mercader, he pioneered the development of a new cryoinjury model to study zebrafish heart regeneration. In October 2013, Dr. Gonzalez-Rosa joined the laboratory of Caroline and Geoffrey Burns at Massachusetts General Hospital and Harvard Medical School. As a postdoctoral researcher, his research was supported by a Long-Term Postdoctoral Fellowship from EMBO and the Funds for Medical Discovery Award from ECOR-MGH. In June 2019, Dr. Gonzalez-Rosa joined the CVRC faculty after receiving the Career Development Award from the American Heart Association.
Dr. Nguyen’s lab focuses on the development and clinical application of novel imaging techniques to evaluate the cardiovascular system including MRI, optical, and PET. Our primary research interests fall into three general areas, in which we develop, clinically translate, and clinically apply new imaging techniques to (1) evaluate myocardial remodeling and regeneration, (2) investigate myocardial metabolism, and (3) characterize vascular biology. The ultimate goal of our research is to empower scientists and clinicians with novel imaging technologies to answer fundamental questions in cardiovascular biology and pathophysiology.
Our lab designs and implements in-house imaging technologies on cutting-edge scanners at the MGH/HST Martinos Center for Biomedical Imaging. We study both large animal models and patients on human clinical systems for immediate clinical translation.
Dr. Nguyen received his PhD in Biomedical Engineering from the University of California Los Angeles in 2015 as a NIH Ruth L. Kirschstein NRSA pre-doctoral fellow. This led to his postdoctoral training at Cedars-Sinai Medical Center and affiliated postdoctoral fellowship at MGH. Subsequently in early 2017, he was promoted to faculty at Cedars-Sinai Medical Center in the Department of Biomedical Sciences and Biomedical Imaging Research Institute. In October 2017, Dr. Nguyen joined the CVRC faculty after receiving the early career NIH NIBIB Trailblazer Award.
Our lab focuses on the molecular mechanisms of the beneficial effects of exercise on metabolism and the brain, with a special interest in secreted factors. The ultimate goal of our research is to identify novel therapeutic targets to combat cognitive impairment in aging or neurodegenerative diseases.
We use various genetic mouse models to dissect the effect of exercise on de novo neurogenesis, synaptic plasticity, and learning and memory. To identify novel pathways we are employing a broad range of cutting-edge technologies, including RNA sequencing, high resolution mass spectrometry, and advanced molecular-based screenings.
Dr. Wrann is an Assistant Professor in Medicine at the Cardiovascular Research Center at Massachusetts General Hospital (MGH) and the Harvard Medical School in Boston. In addition, Dr. Wrann is an affiliate of the Harvard Stem Cell Institute. She is the recipient a K99/R00 Pathway to Independence Award from the NINDS. Her research focuses on the beneficial effects of exercise on metabolism and brain health, and specifically secreted factors as potential drug targets.
Dr. Wrann studied veterinary medicine at the University of Veterinary Medicine Hannover, the University of Cambridge, and Cornell University. She received her Ph.D. with Summa cum laude in Immunology from the University of Veterinary Medicine Hannover in 2008. She concluded her postdoctoral training in the laboratory of Dr. Bruce Spiegelman at Dana-Farber Cancer Institute and Harvard Medical School. In April 2016, she joined the faculty of the CVRC to start her own laboratory.
For recent publications see: Wrann et al. Cell Metabolism 2012, Jedrychowski and Wrann et al. Cell Metabolism 2015, Wrann et al. Brain Plasticity 2015.
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/?reload=addSuccess
Lung injury in newborns and infants often causes abnormal lung development and function. For example, in infants with some forms of congenital heart disease, lung injury causes an abnormal increase in the smooth muscle cells in the blood vessels of the lung periphery and, in part through this mechanism, causes pulmonary hypertension and heart failure. In premature infants, lung injury associated with life-sustaining ventilation of the lungs with oxygen can decrease the development of the peripheral lung and cause bronchopulmonary dysplasia, a chronic lung disease. The long-term goals of my laboratory are to explore the fundamental mechanisms of lung injury and to develop novel therapies for pulmonary diseases in newborns and infants.
Jing-Ruey Joanna Yeh’s research program seeks to identify disease mechanisms and discover effective therapies for cancer and cardiovascular diseases using innovative approaches and zebrafish, cell culture and mouse models. Through a chemical suppressor screen in a zebrafish model of acute myeloid leukemia (AML), the Yeh lab has previously identified that cyclooxygenase-2 (COX-2) inhibitors can suppress self-renewal of leukemia stem cells that express the AML1-ETO oncogene. This finding implies that COX-2 inhibitors may protect against relapse in AML patients. The current research focuses are directed to understand the roles of several metabolic enzymes and their metabolites in oncogenic transformation and heart diseases. Dr. Yeh’s long-term goal is to translate the knowledge obtained in her lab into clinic.
In addition, Joanna Yeh’s research team (in collaboration with Keith Joung and Randall Peterson’s groups at MGH) has also been at the forefront of advancing technologies for zebrafish genome engineering using various customizable site-specific nuclease platforms such as zinc finger nucleases (ZFNs), TALE nucleases (TALENs) and CRISPR/Cas. These technologies make it possible to use zebrafish as a powerful in vivo model for large-scale functional genomics studies.
Dr. Yeh received her PhD from Yale University after studying with Dr. Craig Crews in chemical biology. She then completed a postdoctoral fellowship in the laboratory of Dr. Randall Peterson at MGH. Dr. Yeh is a recipient of the Claflin Distinguished Scholar Award and the Hassenfeld Clinical Scholar Award from MGH. Her research has been published in Nature Chemical Biology, Nature Biotechnology, Cell Metabolism, Nature Methods, PNAS, Blood and others.
You can read an overview of her lab here.