Steven Libutti - Research

Research

Libutti is studying tumor neovascular formation and the interaction between tumor cells, endothelial cells and the components of the tumor microenvironment. The goal of Libutti's research program is to develop novel cancer therapies through a better understanding of the tumor microenvironment. The interaction of a tumor and its vasculature is critical for both tumor growth and the spread of tumor cells to distant organs. The process of new vessel development within the tumor is termed angiogenesis and is required for tumors to grow larger than a few millimeters. In order to better understand the relationship between the tumor and its blood supply, their research is focused on the interaction between tumor-derived factors and endothelial cells developing in the context of the tumor microenvironment. By understanding this interaction they hope to be able to design novel treatment strategies to inhibit both the growth and the spread of tumors. They are currently studying a variety of tumor-derived factors with effects on tumor-associated vasculature. These include vascular endothelial growth factor (VEGF) and endothelial cell monocyte-activating polypeptide II (EMAP-II). EMAP-II is a cytokine with potent effects on blood vessels and was discovered by a research team (including Libutti) at Columbia University. Cytokines such as VEGF and EMAP-II appear to be produced in varying amounts by tumors and have direct effects on the tumor neovasculature. Libutti's approach to the study of these interactions has been through the utilization of a variety of in vitro and in vivo model systems. His team is using gene expression profiling to understand the changes that occur in endothelial cells exposed to tumor-derived factors. His laboratory is developing techniques, which allow them to isolate endothelial cells from tumor tissue. This has resulted in their ability to study tumor-derived endothelial cells directly, and has led to the observation that tumor associated endothelial cells have epigenetic changes compared to normal endothelial cells from the same tissue type. This approach has also allowed them to identify specific genes such as FILIP1L (formerly DOC1), which appear to play a role in the control of endothelial cell responses to angiogenesis inhibitors. They are also using noninvasive imaging techniques, including dynamic MRI and PET, to map changes in tumor blood flow within tumors both in animal models and in patients on clinical trials. A variety of inhibitors of tumor angiogenesis are being actively studied. These include both recombinant proteins derived from naturally occurring substances as well as small molecules designed to act on specific pathways. Various methods of delivering these agents, including gene therapy approaches and the use of tumor targeted nanoparticles are being pursued. Libutti was the first to administer TNF bound colloidal gold nanoparticles as targeted therapy to cancer patients. The overall goal of Libutti's work is to translate a better understanding of tumor cell-endothelial cell interactions, within the context of the tumor microenvironment, into better therapies for patients with cancer.

In addition to his laboratory and research interests, Libutti is an accomplished clinical surgeon. His clinical expertise is in the management of malignancies of the liver, pancreas, and GI tract, and in applying laparoscopic surgery to managing patients with malignancies. In addition, Libutti is an internationally recognized expert in endocrine surgery and provides surgical consultation and treatment for patients with disorders of the thyroid, parathyroid, adrenal glands, and for endocrine tumors arising in the pancreas.