The Greenberg lab is interested in contractile systems, with a focus on cardiovascular disease. We have several projects that we are currently pursuing:
Familial cardiomyopathies:
Familial cardiomyopathies are found in up to 1 in 500 people, and these conditions are the leading cause of sudden cardiac death in young people. In patients with pediatric onset disease, these conditions are especially devastating. Patients with these diseases show alterations in the structural and mechanical properties of the myocardium. Human genetic studies have shown that the most common cause of familial cardiomyopathies is mutation of the proteins involved in generating and regulating force and power output in the heart; however, it is not well understood how changes at the molecular scale lead to alterations in cardiac contractility at the cellular and tissue levels. We have developed molecular, cellular, and tissue-scale models of these diseases, and we are using computational modeling to link these various scales. We are applying our newly gained knowledge to design new precision medicine therapies for these diseases.
Representative publications:
Precision medicine for heart failure:
There are multiple pathways that can lead to heart failure, including iron overload, viral infection, and diabetes. We are trying to understand the mechanisms driving these diseases, and then leverage our mechanistic insights to develop precision medicine therapeutics. We are part of the Cardiovascular Precision Medicine Research Initiative (CPRi) focused on translating basic science knowledge into precision medicine therapeutics for cardiovascular disease. For more information on this initiative, click here.
Representative publications:
Technology development:
Our studies require tools for studying contractility across multiple levels of organization. We are actively developing tools that enable us to model heart contractility at the molecular, cellular, and tissue levels. For our molecular studies, we have developed an optical trapping system with force feedback to study the contractility of single motor proteins. For our cellular studies, we use CRISPR/Cas9 to introduce disease-causing mutations into human stem cells, and then differentiate these stem cells into cardiomyocytes. We use engineering techniques to study the contractility of single cells and to mimic the electrical and mechanical environments of the heart. For our tissue level studies, we are generating human engineered heart tissues in microelectromechanical devices. Importantly, these tools will give us an unprecedented understanding of how the heart generates force and power in both health and disease.
Representative publications:
Immune function in cardiovascular disease:
In collaboration with the Lavine lab, we are studying the role of immune cells in cardiovascular disease. We are building new models to better understand the roles of these cells in promoting both repair and disease progression. This includes our work on the cardiovascular manifestations of COVID-19.
Representative publications:
Molecular motors in health and disease:
Molecular motors power force generation and movement in a wide range of physiological processes including hearing, muscle contraction, and intracellular transport. The function of these motors is tightly regulated, and dysfunction of these motors can lead to a wide range of diseases.
Representative publications: