Laura Benjamin

Department of Pathology
BIDMC
RN 227 D
99 Brookline Ave.
Boston, MA 02215
Tel: (617) 667-5964
Fax: (617) 667-3616
Email: lbenjami@bidmc.harvard.edu

8 postdoctoral fellows, 1 graduate student

In cancer, blood vessels are needed to nourish a growing tumor, bring in inflammatory and immune cells and provide a transportation system for cancer cells to metastasize. Similarly, lymphatic vessels are needed to eliminate waste, traffic immune and inflammatory cells and also provide another route for metastasis. Hence our studies are focused on exploring the basic cell and molecular biology of these vessels and how they can be targeted to improve cancer therapy. In this context we have focused on the Akt signaling pathway and its regulation of the tumor microenvironment.

Our recent work has shown that Akt is a regulator of the pathological phenotype of tumor blood vessels. As an extension of this work, we are exploring the vascular functions of individual proteins in the Akt pathway. In parallel, we are testing whether inhibitors of those proteins will both normalize the diseased vasculature in cancer or inhibit tumor progression through affects on multiple cell types present in the tumor microenvironment. The PI3K/Akt pathway is known to have a profound role in cancer cell biology and is frequently mutated in human cancer. However, its function in the tumor stroma and vasculature is poorly understood and will likely be important in an overall therapeutic approach to treating cancer. We are testing the hypothesis that aberrant signaling from this pathway contributes to multiple stromal dysfunctions that contribute to tumor progression.

A second project that is newer but rapidly expanding in the laboratory is the molecular mechanism regulating the differential development of blood versus lymphatic endothelium. We have found that the GTPase RhoB plays a pivotal role in the development these two related vascular beds. Moreover, we have uncovered a link by which RhoB modulates gene transcription in this process and have several projects available to study both the cell biology and the molecular mechanisms involved in this developmental decision. We are confident that these molecular mechanisms will lead to novel approaches for cancer therapy, especially for the prevention of cancer metastasis.

References:

• Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003. (6):401-10
• Adini I, Rabinowitz I,Sun JF, Prendergast GP, and Benjamin LE. RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development. Genes Dev. 2003 17: 2721-2732
• Sun JF, Phung T, Shiojima I, Felske T, Feng D, Kornaga T, Dor T, Adini, I. Dvorak AM, Walsh K, and Benjamin LE. Microvascular patterning is controlled by fine-tuning the Akt signal. Track II, PNAS 2005. Jan 4;102(1):128-33
• Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Perruzzi C, Sun J-F, Monahan-Early R, Shiojima I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF, Benjamin LE. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell. 2006 Aug;10(2):159-70.