Marc & Ruti Bell Vascular Biology & Disease Program
At NYU Langone’s Marc and Ruti Bell Vascular Biology and Disease Program, we investigate mechanisms involved in the development and progression of cardiovascular disease and related conditions at the cellular and molecular levels. Given the significant health burden of heart disease as the leading cause of morbidity and mortality worldwide, we are particularly concerned with studying factors that will lead to innovations in diagnosis, treatment, and prevention. Led by Edward A. Fisher, MD, PhD, this program uses advanced techniques to explore the biology of vascular diseases.
History and Leadership
The Marc and Ruti Bell Vascular Biology and Disease Program was established by a generous gift from Marc and Ruti Bell in 2003. Based on his extensive research background in lipid and lipoprotein metabolism and atherosclerosis, Dr. Fisher serves as director of the Bell Program to foster research, clinical, and educational advances.
Jeffrey S. Berger, MD, joined the Bell Program in 2014. He currently serves as director of the Center for the Prevention of Cardiovascular Disease. He is an accomplished prevention focused cardiologist who works on platelets and their role in atherosclerosis, heart attacks, and lower extremity peripheral artery disease. His work on platelet activity in other high-risk inflammatory conditions, such as diabetes, systemic lupus erythematosus, and 2019 coronavirus disease (COVID-19) has advanced our mechanistic understanding of these diseases while providing new therapeutic targets.
Kathryn J. Moore, PhD, joined the Bell Program in 2010 and is director of our division’s new Cardiovascular Research Center. She has worked to shed light on the pathways of chronic inflammation and dysregulation in cardiovascular disease, type 2 diabetes, and Alzheimer’s disease.
Working in NYU Langone’s Science Building, our distinguished researchers conduct basic and translational investigations into factors involved in the pathogenesis of cardiovascular disease and associated conditions. Bell Program research activities are funded by a combination of foundation and federal awards, in addition to philanthropy.
Highlights of key research areas include the following.
Cell Biology of Hepatic Lipid and Lipoprotein Metabolism
Dr. Fisher’s team focuses on the regulation of lipids in atherosclerotic heart disease. His lab was the first to demonstrate that degradation of apolipoprotein B (apoB) as regulated by dietary fatty acids may also be regulated by insulin. Importantly, this nonproteasomal pathway may be dysregulated in insulin resistance associated with type 2 diabetes or obesity, thereby contributing to the overproduction of atherogenic lipoproteins that increase the risk of coronary artery disease in these metabolic states.
Dr. Fisher’s work on the assembly process for very-low-density lipoproteins (VLDLs) in liver cells led to the discovery that the amount of VLDL produced depends on how much apoB is degraded in the liver cell. Thus, a therapeutic strategy for lowering the blood levels of high-density lipoprotein (HDL) cholesterol, particularly in those patients either not responsive enough to or tolerant of existing cholesterol- or triglyceride-lowering medications, would be to develop a drug that increases apoB degradation in the liver. The pharmaceutical industry is currently pursuing such an approach.
To further pursue the proteasomal and nonproteasomal regulation of apoB degradation, Bell Program researchers are also using cell and molecular biological approaches and experimental models, including cell-free systems and tissue-specific knockout mice.
Molecular Biology of Vascular Diseases and Noninvasive Imaging Techniques
Scientists in the Fisher Lab investigate the molecular factors that regulate the progression and regression of atherosclerotic plaques. Their research focuses on the regression of plaques after normalization of hyperlipidemia and the effects of HDL on plaque progression and regression. To study the molecular levels that regulate changes in arterial wall cell types, his group is pioneering the use of laser capture microdissection to isolate plaque macrophages to study gene expression. By using novel models and these powerful techniques, they have observed that foam cells can leave plaques during regression and that they require dendritic cell properties for this emigration.
RNA Regulation of Cholesterol and Lipoprotein Metabolism
Dr. Moore’s team pursues research on how noncoding RNA regulates cholesterol and lipoprotein metabolism and other metabolic and inflammatory processes. She and her colleagues were among the first in the world to reveal the role of one type of noncoding RNA called microRNA, microRNA-33 (miR-33), as an inhibitor of cholesterol efflux from cells and in the formation of HDL. In a follow-up project in collaboration with Dr. Fisher, Dr. Moore’s lab also demonstrated that blockers of miR-33 can cause regression of atherosclerotic lesions and raise HDL levels and lower VLDL levels in models, including monkey models. She has also discovered a noncoding RNA that regulates both HDL and LDL metabolism, called CHROME. These findings demonstrate the important role that noncoding RNAs play in metabolism and open new avenues for the treatment of dyslipidemias, obesity, diabetes, and heart disease.
Platelets and Inflammation in Cardiovascular Disease
Dr. Berger and his team study platelets using a variety of techniques, including platelet aggregometry, flow cytometry, hematology analysis, and the platelet transcriptome. The goal of the group is to use the platelet phenotype to understand who is at risk for developing cardiovascular disease and its complications, and to determine whether modification of the platelet phenotype can ultimately lower the risk of adverse cardiovascular events. A collaboration between Dr. Berger and Dr. Fisher focused on the impact of platelets on the progression of atherosclerosis and found that platelets amplify monocyte and macrophage inflammation.
Dr. Berger has partnered with Jill P. Buyon, MD, director of the Division of Rheumatology and worldwide expert in systemic lupus erythematosus. In collaboration, the Berger and Buyon laboratories have shown that platelets are particularly active in systemic lupus erythematosus (SLE) and are involved in the pathogenesis of the condition’s vascular dysfunction. Drs. Berger and Buyon are investigating the link between platelets, inflammation and immunity, and cardiovascular disease in SLE.
Immune Reaction and Inflammation’s Impact on Vascular Pathology, Obesity, and Diabetes
Dr. Moore and Dr. Fisher are studying how specific molecules drive chronic immune reactions in cardiovascular disease and have found that a protein called netrin-1 can promote inflammation and atherosclerosis. New projects arising from this collaboration between Bell Program researchers and the Division of Endocrinology, Diabetes, and Metabolism seek to understand attributes of adipose tissue that may contribute to localized and systemic inflammation and insulin resistance in obesity and atherosclerosis by further exploring the role of netrin-1 and discovering novel factors with similar effects.
Additional Collaborations in Obesity and Diabetes
The Bell Program continues to expand its integrative approach of collaborating with researchers who are conducting related work. We work closely with many researchers in the Division of Endocrinology, Diabetes, and Metabolism, including Ann Marie Schmidt, MD, and Ira J. Goldberg, MD.
With researchers at the Icahn School of Medicine at Mount Sinai, Dr. Fisher’s group has recently shown that HDL particles can be converted to nanoplatforms to deliver MRI-enhancing agents to plaques to better visualize them. Their goal is to adapt these particles for molecular imaging purposes.
Dr. Fisher and his collaborators at NYU Grossman School of Medicine, including Dr. Moore, have shown that, as plaques get smaller, new white blood cells enter and become what are called M2 macrophages, a type of healing cell. The type of information from these collaborative studies may ultimately be useful for clinical diagnostic and therapeutic purposes.
With these distinguished colleagues, our goal is to continue to investigate how macrophages affect diabetes-induced inflammation in atherosclerosis and obesity, and to conduct preclinical investigations of therapies to improve cardiometabolic complications of obesity.
Cardiometabolic Health and Type 2 Diabetes
NYU Grossman School of Medicine is one of only four national scientific teams selected to create a new Strategically Focused Research Network (SFRN) on Cardiometabolic Health and Type 2 Diabetes. These teams focus on scientific work to learn more about heart disease and diabetes in an effort to better prevent and treat these conditions.
Our center scientists, along with colleagues at Mount Sinai, were awarded a $3.4 million center grant to study the link between diabetes and cardiovascular disease. The prestigious American Heart Association SFRN grant will support collaborative projects in the areas of basic science, led by Dr. Fisher; population health, led by Jonathan Newman, MD, MPH, and Chiara Gianarelli MD, PhD, at Mount Sinai; and clinical research, led by Dr. Berger. Dr. Goldberg serves as the center’s director and training director. The research projects, collectively titled “Diabetes and Vascular Disease Repair in Women and Men (REPAIR)” are investigating why people with diabetes do not always benefit from cholesterol-lowering drugs. The researchers also hope to explain why women with diabetes experience a higher occurrence of heart disease and fatal heart attacks than men with diabetes.