Molecular Cardiology Research Institute (MCRI)

Clinical Research: Tufts Medical Center

General Medicine:
Karen Freund, MD, MPH
Brenna McNamara, MD

Cardiology:
Iris Jaffe, MD, PhD
Ayan Patel, MD

Population Research: Tufts CTSI; Friedman School of Nutrition

Community Based Cardiovascular Disease Prevention in Women:
Sara Folta, PhD

Racial Disparities in Cardiovascular Health Interventions:
Linda Hudson, ScD, MSPH

Basic Cardiovascular Science: Molecular Cardiology Research Institute

Vascular Biology, Obesity, Aging, High Blood Pressure:
Iris Jaffe, MD, PhD

Diabetic CardioVascular Complications:
Lakshmi Pulakat, PhD

Sex Differences, Human Vascular Function Studies:
Jennifer DuPont, PhD

Translational Research: USDA Human Nutrition Research Center on Aging

Diet and Cardiovascular Risk in Aging Women:
Alice Lichtenstein, Dsc

Metabolic Biomarkers of Cardiovascular Health and Risk:
Nirupa Matthan, PhD

Iris Jaffe, MD

My research lab is interested in uncovering the molecular mechanisms underlying common vascular diseases including high blood pressure, heart attack, and stroke. I am specifically interested in how common risk factors including obesity, aging, high blood pressure, high cholesterol, and a prior history of high blood pressure during pregnancy (preeclampsia) lead to blood vessels diseases that cause heart attacks and strokes. Women are a rapidly growing part of our aging population and obesity is an epidemic that preferentially affects women. Using animal models and human cells, my lab has discovered profound sex-differences in how blood vessels respond to obesity and aging. We continue exploring the underlying mechanisms with the ultimate goal of developing personalized therapies that will prevent or reverse vascular disease in women with diverse risk factors.

Karen Freund MD, MPH

My research team broadly addresses health disparities among minority and underserved women. Our research methods include outcomes and health policy research to understand the factors associated with poor health outcomes, and interventions to ameliorate these disparities. Recent work includes collaboration with Sasha Fleary PhD on interventions among adolescent girls to address cardiovascular behavioral risk factors including diet, physical activity, and tobacco use. My collaborations with Elena Byhoff MD MS address the mechanisms by which social determinants of health can impact women’s cardiovascular health and how to address them. My own research addresses the impact of insurance reform and insurance stability over the past decade on improved cardiometabolic outcomes for black, Asian, and Latina women.

Jennifer DuPont, PhD

My research interest is to understand and uncover sex differences in the mechanisms of the development of vascular aging. I am specifically interested in sex differences in the development of arterial stiffness and vascular dysfunction with aging. My research also examines the role of sex hormones and their receptors in the development of arterial stiffness and vasomotor dysfunction throughout the lifespan. I use a translational approach to my studies, employing a variety of basic science techniques, preclinical models of disease, and lastly clinical studies examining vascular function in aging men and women. Ultimately, the goal of these studies is to identify novel sex-specific therapeutic strategies to aid in improving cardiovascular disease outcomes in the aging population, especially aging women. These studies are timely and important to improving these outcomes, as the majority of preclinical work has been performed in males only and women have been previously under-represented in larger clinical trials, therefore limiting.

Sara Folta, PhD

The main area of my research is the development and evaluation of community-based cardiovascular disease prevention interventions for midlife and older women. I was a lead researcher on the development and evaluation of StrongWomen – Healthy Hearts, a 12-week program that includes aerobic activity and skill-building for achieving a heart-healthy dietary pattern. As reported in the American Journal of Public Health, this program demonstrated effectiveness in a randomized, controlled trial with rural women in eight counties in Arkansas and Kansas. This work led to a successful bid for Centers for Disease Control funds, allowing us to rigorously evaluate program dissemination in 22 states. We discovered that the program remained effective in a variety of settings; however we also learned African American women were not realizing the same level of benefit from the program as white women. Given that CVD represents one of the most pronounced and alarming health disparities in the United States, I applied for and received two grants to develop heart health programming that is culturally appropriate for African American women. With this funding I have developed and pilot-tested two programs: Healthy Hearts for an Abundant Life and Change Clubs for African American Women.

Linda Hudson, ScD, MSPH

Despite increased risk for cardiovascular disease (CVD) and related conditions, evaluations of health interventions indicate that Black/African American women are less likely to benefit than their white counterparts and are not as likely to engage in behaviors that reduce CVD risk. My research explores interventions to address heart health in Black/African American Women.

Alice H. Lichtenstein, DSc

My research group focuses on assessing the interplay between diet and cardiovascular risk factors, with emphasis on postmenopausal women and older men. Specific research interest centers on how lifestyle modification, particularly diet, can lead to risk reduction. Past and current work includes addressing issues related to trans fatty acids, soy protein and isoflavones, sterol/stanol esters, novel vegetable oils differing in fatty acid profile and glycemic index. Selected issues are investigated in animal models and cell systems with the aim of determining the mechanisms by which dietary factors alter cardiovascular risk factors. Additional work uses samples from population basis studies to address the relationship between biomarkers of cholesterol homeostasis and nutrient intake on cardiovascular disease risk; and on the application of systematic review methods to the field of nutrition. Postmenopausal women are one of the fasted growing demographic groups. Their risk of developing cardiovascular disease increases dramatically with age. It is critical we not only refine methods to treat the disorder but develop approaches to prevent disease progression.

Nirupa R. Matthan, PhD

My research interests are focused on identifying objective biomarkers of diet quality and endogenous metabolism and causal pathways that can be targeted to optimize efficacy of diet-drug therapies to reduce CVD risk. I have expertise in the measurement of cholesterol absorption and synthesis markers, lipoprotein kinetics following dietary modification and targeted lipidomics and metabolomics. Recent projects address the role of carbohydrate and fat type on CVD risk factors, glycemic index, fatty acid metabolism using stable isotopes, the relationship between plasma biomarkers of nutrient intake and diet quality in a family based weight management program, and the effect of avocado consumption on changes in hepatic fat in overweight/obese Americans. Past projects include human metabolic studies on trans fatty acids, soy protein and isoflavones, and novel vegetable oils differing in fatty acid profile on heart disease risk. More recently, I have been involved in elucidating the role of dietary constituents in modulating gut microbiota and derived metabolites on cardiometabolic health.

Ayan R. Patel MD

My areas of interest are in the use of noninvasive cardiovascular imaging for the assessment of vascular and cardiac function. I have a particular interest in the use of noninvasive imaging to understand sex-based differences in cardiac disease and vascular function. Using noninvasive imaging, we have observed differences in vascular endothelial function in men and women, examined the association between vascular function and exercise capacity in women, and examined the association between overweight status and vascular function in women.

Lakshmi Pulakat, PhD, M.Phil., M.Sc

Research in our lab is focused on characterizing cardiovascular reparative signaling pathways that have the potential to repair cardiovascular damage arising either from chronic diseases (diabetes, obesity), or drug treatments (such as chemotherapy). Literature shows that cardiovascular risk is higher in obese and/or diabetic females than age-matched males. We reported that Angiotensin II type 2 receptor (AT2R) that promotes anti-inflammatory signaling is part of the cardiac signature that defines biological sex differences in cardiac signaling in both healthy and diabetic murine models. Our studies identified that the extent of cardiac structural damage and myocardial scarring is higher in female diabetic rats compared to their male counterparts and that diabetes causes suppression of cardiac AT2R expression only in female diabetic rats. We also showed that in young female diabetic rats with intact ovary, any potential cardioprotection from estrogen was not evident as they developed diastolic and systolic dysfunction similar to their male counterparts along with more severe myocardial structural damage. Additionally, we identified microRNA biomarkers that are part of the cardiac signature for biological sex differences in diabetic rats. Based on our published and preliminary results, we hypothesize that a drug that can increase AT2R expression and signaling will induce a cardiac network that will be particularly beneficial to mitigate increased severity of cardiovascular damage in obese and diabetic females. In collaboration with industry we study protective effects of new AT2R agonists that increase AT2R expression and signaling in cardiovascular cells on mitigating cardiac dysfunction and myocardial structural damage in murine models of both sexes. We use cell culturing and animal models for diabetes, combined with genomics, proteomics and bioinformatics approaches to define changes in cardio-protective molecular signature in response to diabetes and drug treatments. Our ultimate goal is to develop new treatment paradigms to mitigate severity of myocardial structural damage (fibrosis, scarring) resulting from metabolic diseases in females.

Trainees:

Lauren Biwer, PhD

I am a postdoctoral scholar in Iris Jaffe’s lab and my research expertise includes molecular and cellular biology, microscopy, and physiological techniques that measure constriction and dilation of isolated, small diameter arteries from mice and humans. Using these techniques, I am exploring the mechanisms and potential therapeutic targets for cardiovascular disease in women with pre-existing risk factors such as pre-eclampsia, obesity, and dyslipidemia.