Cardiology Fellowship - Brigham and Women's Hospital - Harvard Medical School, 2006 Fellowship - Brigham and Women's Hospital - Harvard Medical School, 2007 Research Fellowship - Dana-Farber Cancer Institute, 2009
An overarching focus of the Moslehi laboratory is cardio-oncology or the intersection of cardiovascular disease and cancer. General areas of interest in the laboratory include cardiovascular toxicities that occur as a result of targeted cancer therapies, adverse effects of tumors on the cardiovascular and metabolic systems, cancers that arise from the heart, and the growing appreciation that common risk factors (including genetic mutations) predispose to both cancer and cardiovascular disease. The Moslehi laboratory uses an integrated approach from molecules, cell-based and animal models, and systems biology towards these goals. As well, the laboratory is well integrated to the Vanderbilt cardio-oncology clinical program, with the hope that discoveries in the laboratory will translate into clinical practice.
Cardiovascular Toxicities of Targeted Cancer Therapies-
A major focus of the laboratory is more mechanistic understanding of cardiovascular toxicities that result from novel “targeted” cancer therapies. In this manner, the lab tests the hypothesis that the cardiovascular sequalae of novel “targeted” cancer therapies can provide fundamental insights into human cardiovascular biology (and can potentially inform cardiac drug discovery). Our program brings together basic scientists, translational biologist and clinicians and collaborates closely with oncologists and regulatory agencies nationally and internationally in this effort.
Specific areas of Interest -
1. Kinase Inhibitor-associated cardiovascular toxicity (such as nilotinib or ponatinib) – hypertension, vascular disease
2. Angiogenesis-inhibitors (specifically Vascular Endothelial Growth Factor – VEGF – signaling pathway inhibitors, such as bevacizumab or pazopanib) – hypertension, thrombosis, cardiomyopathy
3. Drugs that target protein degradation – Immunomodulators (such as lenalidomide) and proteasome inhibitors (such as carfilzomib) – hypertension, thrombosis
4. Cancer immunotherapies – myocarditis, vascular toxicity
Myotoxicity associated with immune checkpoint inhibitors-
The Moslehi laboratory has defined a new clinical syndrome of myotoxicity associated with cancer immune checkpoint inhibitors. This syndrome can present with development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and fulminant myocarditis with a robust presence of T-cell and macrophage infiltrates. We have started studies exploring the mechanisms of this new clinical syndrome, why certain cancer patients are especially at risk and the implications of this syndrome for other cardiac diseases, including other types of myocarditis and cardiac transplant rejection. Additionally, preliminary data suggest that the targets of immune checkpoint inhibitors, PD-1/PD-L1 may play a critical role in the cross talk between the cardiovascular and immune systems.
Cancer Affecting or Arising from the Cardiovascular System-
Certain cancers can have adverse effects on the cardiovascular system or may arise from cardiac tissue. For example, carcinoid tumors can affect the heart, resulting in valvular heart disease and heart failure. Other tumors can cause myocyte (both skeletal muscle and cardiac) atrophy resulting in cachexia. In other cases, cardiac tumors can arise from the heart itself. Using clinical samples collected both at Vanderbilt and in collaboration with other centers, we are dissecting the mechanisms by which cancers can interact with the cardiovascular systems in these ways.
Vanderbilt Cardio-Oncology Program-
A unique aspect of the laboratory environment is the close interaction of the laboratory with the Vanderbilt cardio-oncology program. The program now includes a clinical fellowship as well as a multidisciplinary approach to patient care with a close working relationship between cardiologists and oncologists.