Gera Neufeld, PhD
Professor of Cell Biology
PhD, 1985 - Hebrew University, Israel
Molecular mechanisms that contribute to the development and progression of cancer
My laboratory investigates molecular mechanisms that contribute to the development and progression of cancer. Two ongoing projects are focused on: (1) the semaphorins, and (2) Loxl2.
Previously we were the first to demonstrate that an axon guidance factor of the semaphorin family, sema3F, possesses potent anti-angiogenic and anti-tumorigenic properties. Subsequent studies have shown that several class-3 semaphorins share these properties. Currently, we are studying the mechanisms whereby these semaphorins affect angiogenesis, lymphangiogenesis and tumor metastasis.
In earlier studies we discovered that a member of the lysyl-oxidase gene family, the enzyme Loxl2, plays an important role in the regulation of tumor metastasis and fibrosis. Notably, a drug targeting LOXL2 was developed based upon these findings (simtuzumab) and is now in clinical trials. Work in the laboratory is currently focused on the molecular mechanisms used by Loxl2 and other lysyl-oxidases to promote tumor metastasis. In addition, we are characterizing the genes that are regulated by such lysyl-oxidases.
Mumblat Y, Kessler O, Ilan N, and Neufeld G. 2015. Full length semaphorin-3C is an inhibitor of tumor lymphangiogenesis and metastasis. Cancer Research 75, 2177-2186.
Sabag AD, Smolkin T, Mumblat Y, Ueffing M, Kessler O, Gloeckner CJ, and Neufeld G. 2014. The role of the plexin-A2 receptor in semaphorin-3A and semaphorin-3B signal transduction. J. Cell Sci. 127, 5240-5252.
Zaffryar-Eilot S, Marshall D, Voloshin T, Bar-Zion A, Spangler R, Kessler O, Ghermazien H, Brekhman V, Suss-Toby E, Adam D, Shaked Y, Smith V, and Neufeld G. 2013. Lysyl Oxidase-Like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours. Carcinogenesis. 34, 2370-2379.
Neufeld G, Sabag AD, Rabinovicz N, and Kessler O. 2012. Semaphorins in angiogenesis and tumor progression. Cold Spring Harb. Perspect. Med. 2, a006718.
Casazza A, Kigel B, Maione F, Capparuccia L, Kessler O, Giraudo E, Mazzone M, Neufeld G*, and Tamagnone L.* 2012. Tumor growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin-3E isoform. EMBO Mol. Med. 4, 234-250. (*corresponding authors)
Inhibition of LOXL2 expression in highly metastatic tumor cells inhibits their invasiveness.
Panel A. A novel tumor cell invasion assay is illustrated in which tumor cells are placed between two layers of collagen and allowed to invade. The gel is then sectioned perpendicularly and the degree of invasion assessed.
Panel B. Expression of LOXL2 was inhibited in highly invasive HT-1080 chondrosarcoma cells and in LM2-4 breast cancer cells using specific shRNA targeting LOXL2. Using the invasion assay shown in A, it can be seen that this downregulation of LOXL2 results in strong inhibition of invasion of the collagen layers.
Panel C. Quantification of the experiment shown in B. Inhibition of invasiveness is highly significant statistically (** p<0.01).