The vascular function core is equipped with two 4-channel DMT wire myograph systems and 3 Living Systems pressure myograph system for the assessment of arterial function. Additionally, the clinical vascular function laboratory is equipped with a Moor Instruments Laser Doppler Flowmetry system with intradermal microdialysis for the assessment of human skin blood flow, an index of microvascular function and a Sphygmocor System for the assessment of vascular stiffness via pulse wave velocity and pulse wave analysis.

The facility is comprised of four separate rooms. The first and largest room is equipped with four independent and fully functional murine ‘operating stations’, each with a surgical stereomicroscope, tabletop gas anesthesia machine for rodent inhalation anesthesia, fiber optic lighting, temperature regulation with feedback control via rectal temperature monitoring, microsurgical instruments, heat pad and heat lamp, glass bead sterilizers, surgical supplies, shaver and weighing scales. In addition, there is a rodent respirator for use in open chest procedures and a Millar pressure volume hemodynamics area associated with one of these workstations. One of these four stations is primarily dedicated to closed chest survival electrophysiology studies.

The second room functions as the telemetry room. This temperature and humidity-controlled site includes the DSI equipment necessary to perform continuous ambulatory telemetric EKG and hemodynamic monitoring along with constant measurement of animal temperature and activity. The current room capacity allows for simultaneous measurement of two groups of eight mice.

A third room houses two Kent Coda mouse tail cuff blood pressure analysis systems with laptop computers and capabilities of noninvasively measuring 12 mice simultaneously.

The fourth room houses a VisualSonics ultrasound machine with an associated tabletop gas anesthesia machine, a heated platform with EKG and a micromanipulator for injections. This area contains two separate anesthesia platforms to enable echocardiography on either mice or rats. The room also houses a Dexa imager capable of measuring bone density and body composition of mice.

The facility also has access to a mouse exercise treadmill capable of exercising six mice simultaneously.

The Interventional Research Core Laboratory has a fully equipped and accredited animal hybrid interventional-operating fluoroscopy suite capable of routine and fluoroscopic imaging for large animal work. Housing is located on an adjacent floor. The facility has all of the equipment necessary for multivessel physiology and invasive hemodynamic studies and studies involving mechanical circulatory support.  It is led by an Interventional Cardiologist and staffed by a pre-clinical surgeon, a DVM research associate and two experienced large animal technologists. The team works closely with the Director of the Tufts Comparative Medicine Services (Tufts CMS), a veterinarian with more than 30 years of small and large animal research experience. Animals are examined at least daily by the veterinarian staff and research personnel according to the AAALAC and NIH guidelines. In addition, Tufts CMS animal histopathology laboratory has dedicated pathology staff to support studies in the Core.

The core maintains a large variety of cryopreserved cell lines. There are over 500 different primary cell lines (SMC, EC and fibroblasts) isolated from 92 different types of tissue, primarily human and transgenic mouse vascular tissue. There is also a stock of commercially purchased established cell lines available to MCRI Investigators.

The tissues are processed and stored and the associated clinical database is curated by the MCRI Core lab staff. Applications for the use of collected samples from MCRI scientists are reviewed by a committee to ensure efficient use of this resource and that the highest standards of scientific and ethical conduct are met. The names and identities of patients and participants are never disclosed as part of this research. Studies completed using samples from the MCRI tissue bank have contributed to our knowledge of diverse topics including aortic valve disease, genetic cardiomyopathy, peripheral vascular disease, atherosclerosis and cardio-oncology.

The ultimate goal is to translate these fundamental discoveries into novel therapies to prevent or treat vascular diseases that contribute to heart attack, stroke, high blood pressure, peripheral arterial disease and other common cardiovascular conditions. The Center is particularly focused on the impact of age, sex, and risk factors including obesity and diabetes on blood vessel function. The VBRC maintains a highly collaborative environment, allowing investigators to share ideas, reagents, approaches and models to bring a multidisciplinary approach to solving important unanswered questions in vascular biology in a highly translational context.

VBRC uses a wide range of approaches, including state-of-the-art molecular biology, global genomic, proteomic, and epigenetic technologies, cell biology, whole vessel wire and pressure myography, sophisticated transgenic mice and in vivo animal models of vascular diseases and human vascular function studies. The Center works closely with the MCRI Cell Culture Core Lab, Vascular Function Core Lab and the Biobanking Core lab.

VBRC laboratories are actively studying vascular mechanisms contributing to:

• Vascular inflammation and atherosclerosis
• Hypertension
• The impact of risk factors on blood vessels, including obesity, hyperlipidemia, and hypertension
• Aortic aneurism formation and progression
• Vein graft and stent failure
• Pulmonary hypertension
• Sex differences in cardiovascular disease
• Vascular changes with normal and pathologic aging

The VBRC maintains a highly collaborative environment, allowing investigators to share ideas, reagents, approaches and models to bring a multidisciplinary approach to solving important unanswered questions in vascular biology in a highly translational context. Application to human disease is central to the approach involving collaboration with clinicians to accelerate the development of biomarkers and new molecular targets for the diagnosis and treatment of vascular disease.

Vascular Biology Research Center labs

Dupont Laboratory
Jennifer Dupont, PhD
Research Interests: Vascular Function, Estrogen, Aging, Arterial Stiffness, Sex Differences in Cardiovascular Disease
Email: Jennifer.Dupont@tuftsmedicine.org

Good Laboratory
Miranda Good, PhD
Research Interests: Stroke, Alzheimer's disease, Neurovascular Function, Neuroinflammation, Cerebral Blood Flow Regulation, Pannexin1 Channels
Email: Miranda.Good@tuftsmedicine.org

Icli Laboratory
Basak Icli, PhD
Research Interests: Obesity, Type-2 Diabetes, Acute Myocardial Infarction, Wound Healing, MicroRNA, Angiogenesis, Inter-organ Cross-talk, Brown Adipose Tissue
Email: Basak.Icli@tuftsmedicine.org

Jaffe Laboratory
Iris Jaffe, MD, PhD
Research Interests: Atherosclerosis, Hypertension, Vascular Biology, Aging, Sex Differences in Cardiovascular Disease, Mineralocorticoid Receptors, Cardio-oncology
Email: Iris.Jaffe@tuftsmedicine.org

Ongoing studies have clinical applications in cardiovascular, inflammatory, metabolic and skeletal muscle disease. Work performed by the Center laboratories includes (i) state-of-the-art genomic approaches (e.g. ChIP-seq, RNA-seq, RNAi), (ii) generation and analysis of invertebrate (Drosophila) and vertebrate animal models of human diseases, (iii) structure-function studies on a wide variety of pharmacological targets (receptors, channels, enzymes) and (iv) development of novel tools enabling peptide and small molecule drug discovery. The wide array of research capabilities featured by the Center laboratories naturally extends beyond the boundaries of one organ system or pathway offering the unique ability to understand many complex and/or inherited chronic diseases.

The Center Investigators hold faculty positions in the Tufts University School of Medicine graduate programs and regularly mentor Masters, PhD-level thesis students and Post-Doctoral Fellows in Pharmacology, Genetics, Clinical Translational Sciences and Cell, Molecular and Developmental Biology.

The primary goal of this laboratory is to make discoveries relevant to human diseases for the purpose of understanding the biology of human development and disease that in addition to providing greater insight into mechanisms of disease may also translate to improved diagnostics and therapies. We seek to make our primary discoveries by studying human DNA and/or tissues. Genes or pathways identified through discovery work based on human samples then serve as the basis for traditional hypothesis-oriented research in animal and cellular model systems employed by my laboratory.

Center for Translational Pharmacology + Genomics labs

Draper Laboratory
Isabelle Draper, PhD
Research Interests: RNA splicing, Muscular Dystrophy
Email: Isabelle.Draper@tuftsmedicine.org

Huggins Laboratory
Gordon Huggins, MD
Research Interests: Genetics, Cardiomyopathy, Heart Failure, Valve Disease, Atherosclerosis
Email: Gordon.Huggins@tuftsmedicine.org

Pulakat Laboratory
Lakshmi Pulakat, PhD
Impact of Obesity and Diabetes on the heart, Wound Healing, Sex Differences in Cardiovascular Disease, Angiotensin Type 2 Receptors, G protein-coupled Receptors, Drug Development
Email: Lakshmi.Pulakat@tuftsmedicine.org

In addition to fundamental discovery, a major objective of the CBRC is to translate these discoveries into novel therapeutic targets to limit the onset and progression of cardiovascular disease. The CBRC maintains a highly collaborative environment with rich areas of cross-pollination with the Vascular Biology Research Center and Center for Translational Pharmacology and Genomics. Strong relationships between the CBRC, the Surgical and Interventional Research Laboratories (SIRL), the Cardiovascular Biobank and the CardioVascular Center have accelerated the translational of several fundamental discoveries into large animal models and subsequently into early-phase clinical trials.

The CBRC employs a wide variety of cutting-edge technology and pioneering techniques to achieve its core mission of fundamental discovery. A central CBRC resource is the Mouse Physiology Core, which conducts advanced hemodynamic studies involving non-surgical univentricular and biventricular pressure-volume loop analysis, electrophysiologic mapping, univentricular and biventricular pacing, 3D and strain imaging echocardiography, murine cardiac magnetic resonance imaging, and isolated Langendorf cardiac preparations. The mouse core also performs multiple models of cardiac injury in mice including thoracic and pulmonary artery banding, pharmacologically induced pulmonary and systemic hypertension, acute myocardial infarction, coronary ischemia-reperfusion injury, renal ischemia-reperfusion injury, unilateral ureteral obstruction, and arterio-vascular shunts.

The CBRC also maintains a rich library of transgenic mouse models for constitutive and inducible manipulation of genetic targets. In collaboration with the SIRL, the CBRC also studies large animal models of coronary ischemia-reperfusion injury and rapid unipolar or bipolar pacing. This unique resource provides investigators with full interventional or cardiac surgical capabilities to study the biological impact of device-based approaches for heart failure including mechanical circulatory support devices. CBRC investigators have also developed techniques for the isolation of atrial and ventricular myocytes, fibroblasts, and Purkinje cells and have expertise in in vitro ischemia-reperfusion injury, cyclic mechanical stretch and strain studies, and single-cell RNA-seq analysis. In summary, the fertile and nurturing environment of the CBRC enables investigators to focus on translating fundamental discoveries into novel therapeutic and diagnostic approaches for millions of individuals suffering from cardiovascular disease worldwide.

CBRC labs

Blanton Laboratory
Robert Blanton, MD
Research Interests: Heart Failure, Cardiomyopathy, Molecular Signaling, cGMP, Protein Kinase G, Cardiac function, Cardiovascular disease, Mixed Lineage Kinase 3
Email: Robert.blanton@tuftsmedicine.org

Chen Laboratory
Howard Chen, PhD
Research Interests: Autophagy, Apoptosis, Molecular Imaging, Theranostic nanoprobes, Cardio-oncology, Cardioprotection, Cardiomyopathy, Heart Failure
Email: Howard.Chen@tuftsmedicine.org

Chin Laboratory
Michael Chin, MD, PhD
Research Interests: Hypertrophic and genetic cardiomyopathies, Barth Syndrome, Heart Failure, Genetics, Genomics, Molecular Biology, Transcriptomics, Proteomics
Email: Michael.T.Chin@tuftsmedicine.org

Galper Laboratory
Jonas Galper, MD, PhD
Research Interests: Metabolic Heart Disease, Impact of Type II Diabetes and Metabolic Syndrome on the Heart, Heart Failure with Preserved Ejection Fraction, Ventricular Tachycardia, Atrial Fibrillation, Ion Channel Dysfunction, Calcium Signaling
Email: Jonas.Galper@tuftsmedicine.org

Kapur Laboratory
Navin Kapur, MD
Research Interests: Heart Failure, Cardiogenic Shock, Cardiac Fibrosis, Heart Failure Device Development, Impact of Circulatory Support Devices on Cardiac Molecular Biology
Email: Navin.K.Kapur@tuftsmedicine.org