E Gherardi, R Pizzala, C Scotti, L Stivala

Cell behaviour in regeneration and cancer

The formation of the body plan of complex multicellular organisms depends upon an extensive network of intercellular

signals that control the migration, survival, division and fate of each cell in the body. The migration of neural crest cells

from the dorsal neural tube, that of myogenic precursor from the epithelial dermomyotome and the migration of cancer

cells to distant organs depend crucially on complex signalling system.

Our laboratory works on HGF/SF–MET, a signalling a system essential for cell growth, differentiation and migration in

embryogenesis (see Fig) and for cancer spreading. We have studied the cell biology of HGF/SF-MET signalling in

previous years and its physiological roles through gene targeting experiments.

The laboratory now focuses on three lines of investigation:

(i) crystal structure of HGF/SF and MET as the basis for understanding the structural basis of receptor activation

(ii) protein engineering of HGF/SF in order to produce stable MET agonists for application in tissue and organ engineering

(iii) development of antibodies and small molecule receptor antagonists for application in metastatic cancer.

Selected Papers

Michael Stoker 1918-2013. Weiss RA and Gherardi E.

Cell 155: 493-4 (2013)

Targeting MET in cancer: rationale and progress. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G.

Nature Rev Cancer 12: 89-103 (2012)

Structural basis for agonism and antagonism of hepatocyte growth factor. Tolbert WD, Daugherty-Holtrop J,

Gherardi E, Vande Woude G, Xu HE.

Proc Natl Acad Sci U S A 107:13264-9 (2010)