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.
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. Pradeep Natarajan is a preventive cardiologist, cardiovascular geneticist, and physician-scientist. He is the Director of Preventive Cardiology at Massachusetts General Hospital.
Coronary heart disease is a major cause of morbidity and morbidity worldwide. We use naturally-occuring human genetic variation, biomedical informatics, integrative genomics, and genotype-based deeper phenotyping to gain insights about cardiometabolic traits. We use the following approaches to use human genetic variation to understand human disease: 1. identify causal factors that influence disease, 2. test epidemiological associations for causal inference, 3. disease risk prediction, 4. therapeutic response prediction, and 5. discover and characterize the range of phenotypic consequences of putative therapeutic targets. Such analyses are done through clinical recruitment, family-based studies, observational prospective cohorts, case-control cohorts, large-scale health-care associated biobanks, and randomized controlled clinical trials. We aim to leverage novel insights to improve preventive cardiovascular care.
Dr. Natarajan received his B.A. in Molecular & Cell Biology from the University of California, Berkeley (2004), M.D. from the University of California, San Francisco (2008), and M.M.Sc. in Biomedical Informatics from Harvard Medical School (2015). He completed internship and residency in Internal Medicine at Brigham & Women’s Hospital (2011) and cardiovascular diseases fellowship at Massachusetts General Hospital (2015). He completed post-doctral training in human genetics at the Massachusetts General Hospital and Broad Institute of Harvard & MIT.
Cardiac arrhythmias are a leading cause of morbidity and sudden death, and collectively constitute a substantial public health problem. We are focused on understanding the inherited basis of cardiac arrhythmias and applying discoveries to improve outcomes in patients with these conditions. Our research spans disciplines involving human genetics and epidemiology. Several areas of active investigation include:
Determining the genetic basis of heritable arrhythmias: Using genotyping and sequencing techniques, we aim to determine genetic factors that underlie atrial fibrillation and arrhythmias associated with sudden cardiac arrest, including the long QT syndrome, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia, dilated cardiomyopathy, left ventricular noncompaction, and others.
Characterizing the long-term course of atrial fibrillation: By characterizing the long-term course of patients with atrial fibrillation, and by identifying factors that associate with clinical outcomes, we aim to identify strategies to improve the care of patients with this common arrhythmia.
Improving risk stratification and treatment of individuals with inherited arrhythmias: We are studying approaches to tailor the care of patients with inherited arrhythmia conditions in order to minimize the risk of sudden cardiac arrest.
Our laboratory is primarily interested in the clinical expression and molecular etiology of human aortic aneurysm. Aneurysm represents the anatomic expression of aortic organ failure with dilation and eventual tear; an event termed “dissection” associated with high mortality. In our research we use human and murine genetics as well as animal modeling to investigate the etiology and pathologic progression of inherited and sporadic aortic disease. Through our findings we hope to discover better diagnostics and novel therapies for patients with aneurysmal conditions.
The goal of our laboratory work is to use genetics to elucidate the molecular basis underlying abnormalities of the heart rhythm and heart function. Much of our recent work has focused atrial fibrillation which is the most common arrhythmia. To identify novel pathways for atrial fibrillation we are using a broad range of techniques including population genetics, electrophysiology, and animal models of arrhythmias.
This work in turn led the establishment of the AFGen Consortium, an international group of investigators studying the genetics of atrial fibrillation. In the ensuing years, we have led large-scale genetic analyses for atrial fibrillation and many other cardiovascular diseases. Our work now spans a wide range of topics centered on cardiovascular disease genetics, mechanisms, single cell sequencing, and therapeutic development.
Dr. Newton-Cheh is a complex trait geneticist and cardiovascular epidemiologist, as well as a practicing cardiologist. His laboratory investigates hypertension, sudden cardiac death and cardiotoxic drug response as manifest in the electrocardiographic QT interval. He has led several international consortia that have identified scores of novel genetic factors contributing to hypertension, myocardial repolarization and sudden cardiac death in work published in Nature Genetics, Nature, with many additional high-impact publications in JAMA and the New England Journal of Medicine. He has received awards from MGH for his highly collaborative science efforts to characterize the role of natriuretic peptides in blood pressure regulation, spanning the Center for Human Genetic Research, the Cardiology Division and the Department of Anesthesia, Critical Care and Pain Medicine.
Dr. Newton-Cheh’s finding of eight genetic loci related to blood pressure was highlighted as one of the ten most important discoveries of 2009 by the American Heart Association. He is currently leveraging the rapid growth of human genetics to identify genetic variants in genes known and previously unknown which underlie cardiac diseases, and to translate these genetic discoveries into an improved understanding of human physiology through clinically-focused research. This important work seeks to define the role of genetics and other factors in predicting patients’ risk of disease and cardiotoxic drug response. He has several ongoing physiological trials in humans to better understand the mechanisms by which common variants contribute to the development of disease.
To read more about his science, click here.
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.