Universitair Medisch Centrum UTRECHT (UMCU)

Short name: UMCU
Full name: Universitair Medisch Centrum UTRECHT 
Address: Heidelberglaan 100, 3584CX Utrecht, Netherlands
Principal investigator/contact: Dr. Johan de Rooij

The University Medical Center Utrecht is a public healthcare organization, the Center for Molecular Medicine is a division within this organization that houses a number of research labs that conduct fundamental cancer research. Within the Oncology area, the Department of Pathology focuses on breast and colon cancer. Fundamental research, mouse models and preclinical intervention studies form the basis for breast cancer research, led by Prof Paul J. van Diest and Dr. Patrick Derksen.

Team Leader, Dr. Johan de Rooij received his PhD from Utrecht University in 2000, where he identified a family of Guanine-nucleotide Exchange Factors, among which the cAMP-target Epac. Based on this work, a start-up pharmaceutical company, Semaia, was founded, where he was employed from 2000-2002. In the meantime Johan was awarded a fellowship from the Dutch Cancer Society (KWF) to study the balance between cell-cell and cell-matrix adhesion during malignant transformation at the Scripps Research Institute in La Jolla (USA) (2002-2005). In 2005 he returned to the Netherlands to continue this line of research at the Netherlands Cancer Institute and moved in 2008 to the Hubrecht Institute to become a junior group leader and expand his work on the regulation and mechanics of cell adhesion. In 2014, He moved to the University Medical Center Utrecht where his research group investigates the biophysical regulation of morphogenesis and tumor transformation using the novel organoid technology. Johan has published 46 SCI-indexed journal papers and has an h-index of 27 and >4500 citations (according to Web of Science). His key discoveries are:

• Epac, a novel target for the second messenger cAMP (De Rooij et al, Nature, 1998)

• 007, an Epac selective cAMP analog widely used in research labs (De Rooij et al, Nature Cell Biology 2003)

• Mechical regulation of metastatic cell behaviour in 2D culture (De Rooij et al, JCB 2005)

• E-cadherin is a mechanosensor (Le Duc et al, JCB 2010)

• Cell-cell adhesion stability is controlled by mechanical activation of vinculin (Huveneers et al, JCB 2012)

Co-PI, Dr. Patrick Derksen received his PhD in 2003 on cell signaling by adhesion receptors in lymphoid malignancies (AMC Amsterdam). After a postdoc at the Netherlands Cancer Institute, he received personal awards from NWO (Veni and Vidi), which instigated his independence from 2007 onwards at the UMC Utrecht. Research in the Derksen lab has unraveled the basis for metastatic disease in lobular breast cancer, by showing that somatic inactivation of E-cadherin is causal to the p120-dependent development and progression of this disease (Cancer Cell, 2006; Disease Models and Mechanisms, 2011 and Journal of Clinical Investigation, 2011). Mechanistic insight was further provided through the identification of Wnt11 as a p120/Kaiso-dependent autocrine driver of RhoA (Disease Models and Mechanisms, 2015). Further, his group identified BMF as a novel and constitutively repressed FOXO3 target in E-cadherin deficient cells (Cell Death and Differentiation, 2016). His lab is now now are performing the final translational step by testing a novel preclinical and clinical targeted intervention strategy targeting Rock, PI3K/AKT and BCL2 in lobular breast cancer at the UMC Utrecht Mouse Cancer Clinic, of which Patrick Derksen is head.

Oncogenic FER kinase has been identified as a key prognostic factor in lymph node-negative high grade breast cancer by his group, a finding was functionally linked to integrin α6β4-depdendent control of metastasis using in vitro and in vivo models (Oncogene, 2013). Most recently his lab revealed p120 as a tumor suppressor by using conditional mouse models, cell biology and biochemistry (Cancer Research, 2013).

In short, his lab uses a unique combination of biochemistry, cell biology and mouse modeling for the clinical translation of key molecules that link aberrant cell-cell and cell-matrix adhesion to cancer progression. Patrick Derksen has published 37 SCI-indexed journal papers with an average citation of 54.5, an average impact factor of 11.2 and an h-index of 21. (according to Web of Science).