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.
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.
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
The laboratory focuses on the role of immunity in cardiovascular disease, specifically in atherosclerosis and heart failure. Of particular interest are the supply and production of leukocytes by the hematopoietic system, and the signals that regulate hematopoiesis after ischemic injuries such as myocardial infarction or stroke. We described that after myocardial infarction, the spleen releases a large population of ready-made leukocytes that travel to the ischemic heart (Science 2009). We further found that after myocardial infarction, increased sympathetic nerve activity modulates the hematopoietic stem cell niche, activating migration and proliferation of myeloid progenitor cells. This, in turn, accelerated the progression of atherosclerosis (Nature 2012), possibly explaining why secondary infarcts are so common in patients. We are interested in identifying and blocking danger signals arising from ischemic injury, including neural signals that amplify systemic inflammation. The laboratory also develops and employs imaging approaches to sample biology non-invasively, using MR, nuclear, optical and hybrid imaging.
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.
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.
Our experimental laboratory is developing bench-to-bedside approaches to image and understand in vivo inflammation and thrombogenesis in vascular disease, including atherosclerosis, venous thrombosis, and arteriovenous fistula. Via close collaborations with molecular imaging chemistry, we have developed an array of molecular imaging agents to report on macrophages, fibrin, cathepsin K, VCAM-1, thrombin, and activated factor XIII. Using intravital microscopy, FMT, MRI, or PET-CT we have imaged and quantified these molecular targets in murine models of vascular disease, which have led to new insights into how atheroma, thrombi, and AVF evolve and resolve.
Our major translational focus is the development of intravascular near-infrared fluorescence molecular imaging catheter technology to image inflammation in human coronary arteries and coronary stents, using large animal models. In conjunction with leading engineering groups, we have developed intravascular NIRF-OCT and NIRF-IVUS catheters and systems. The ability to image inflammation at high-resolution could provide new approaches to identify high-risk plaques and high-risk stents.
Clinical research efforts are focused in improving percutaneous coronary intervention success for chronic total occlusions, radial artery catheterization, and improving the treatment of microvascular coronary disease / microvascular angina.
Dr. Jaffer graduated from Stanford University (1990, BS with distinction in Mathematical and Computational Sciences) and received his M.D. and Ph.D. in Biophysics from the University of Pennsylvania School of Medicine in 1996. He was a Howard Hughes Medical Institute-NIH Research Scholar from 1993-1995. Dr. Jaffer completed a residency in internal medicine at the Brigham and Women’s Hospital (1999) and went on to a fellowship in Cardiovascular Medicine at Massachusetts General Hospital (1999-2001). Dr. Jaffer completed a postdoctoral research fellowship in the Center for Molecular Imaging Research at MGH, directed by Professor Ralph Weissleder, M.D. Ph.D. followed by a fellowship year in Interventional Cardiology. In 2003, Dr. Jaffer joined the MGH Cardiology Division as a faculty member. In 2006, he was promoted to Assistant Professor of Medicine at Harvard Medical School. In 2007, Dr. Jaffer was appointed as a Principal Investigator in the Cardiovascular Research Center at MGH. In 2011, he became an affiliated Faculty Member in the MGH Wellman Center for Photomedicine. In 2012, he was promoted to Associate Professor of Medicine at Harvard Medical School. In 2013, he was elected to the American Society for Clinical Investigation.
I received my MD in Siberian State Medical University (Tomsk) and PhD in Institute of Evolutionary Physiology and Biochemistry (St.Petersburg) in Russia. I was postdoctoral fellow in Institute of Environmental Medicine of University of Pennsylvania (laboratories of Drs. D. Buerk, S. Thom and V. Muzykantov) and in CVRC of MGH (laboratory of Dr. P. Huang), where I was promoted to Instructor and Assistant Professor.
My research combines mouse genetics, detailed physiologic and hemodynamic measurements, and animal models of human disease, including stroke, atherosclerosis, and diabetes.
My current work focuses on the role of Akt-eNOS-cGMP axis in cerebrovascular dysfunction. My publications demonstrated that mice that carry specific S1177D mutation in eNOS gene are protected against stroke (Journal of Clinical Investigation, 2007), and that they show less obesity and metabolic abnormalities on high fat diet (Biochemical and Biophysical Research Communications, 2013). We show that unphosphorylatable eNOS impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse metabolic profile, suggesting that S1177 eNOS is protective in ischemic stroke. We have found that increased phosphorylation of eNOS on serine 1177 normalized vascular abnormalities in type 2 diabetic mice and protect them against reperfusion injury (Stroke, 2013).
I demonstrated that sGC alpha 1 deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, indicating that cGMP generated by sGC alpha1 is protective in ischemic stroke (Stroke 2010). The hydrogen clearance method of absolute cerebral blood flow measurement which I use provides absolute measurements as opposed to relative measurements seen with laser Doppler or other commonly used approaches. It has become more accepted, as comparison of genetically altered mice with control animals requires consideration of baseline physiologic differences. I used the hydrogen clearance technique to assess the state-of-the-art novel method of Doppler optical coherence tomography in cerebrovascular physiology (Journal of Cerebral Blood Flow and Metabolism 2011).
We demonstrated that C-reactive protein, a widely accepted marker of cardiovascular diseases, causes insulin resistance through Fcγ receptor IIB-mediated inhibition of skeletal muscle glucose delivery (Diabetes 2012). I showed that C-reactive protein increases the severity of stroke outcome (International Stroke Conference 2012). This demonstrates that C-reactive protein is not just a marker, but also plays a mechanistic role in cerebrovascular and cardiometabolic diseases, opening the possibility for additional treatment and prevention strategies.
The overall unifying theme behind my work is to apply in vivo physiology and disease models and in vitro vascular reactivity measurements, to genetic models relevant to the NO pathway, such as nNOS, eNOS, iNOS, soluble guanylate cyclase, and C-reactive protein. My work is important because it can lead to the development of new approaches to treat cardiovascular and cerebrovascular disease in the setting of diabetes and metabolic abnormalities.
Dr. Rajeev Malhotra graduated from Harvard College in chemistry and physics and obtained a masters degree in chemistry and chemical biology from the Harvard Graduate School of Arts and Sciences. He received his medical degree from the Health Sciences and Technologies Division of Harvard Medical School. Dr. Malhotra completed residency in internal medicine and fellowship in general cardiology at the Massachusetts General Hospital. He then completed a post-doctoral fellowship with Dr. Kenneth Bloch.
Atherosclerosis and peripheral vascular disease affect more than 40 million people in the United States and is the number one contributor to morbidity and mortality. Although treatments exist that target risk factors for cardiovascular disease (such as dyslipidemia or anti-hypertensives), there is currently no treatment to directly prevent or reverse vascular calcification. Dr. Malhotra’s laboratory studies the molecular mechanisms by which calcification develops in the vessel wall. Specifically, he investigates bone morphogenetic protein signaling and its role in the development of systemic vascular disease in multiple models, including that of matrix gla protein deficiency and low-density lipoprotein receptor (LDLR) deficiency. More recently, Dr. Malhotra’s laboratory has been studying the overlapping molecular mechanisms of calcific vascular disease and dysregulated lipid metabolism.
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.