Post-doctoral researcher position at the Department Cell and Chemical Biology, Leiden University Medical Center.
Project description: Chemical biological approaches to redirect TGF-b signaling
Transforming growth factor-b (TGF-b) is of key importance in development and maintenance of tissue homeostasis. Work in the Ten Dijke lab is focused on the understanding how TGF-β signaling is perturbed in cancer, and to find new ways to target this pathway for therapeutic gain.
Suitably qualified researchers are invited to apply for a post-doc position focused on the development of synthetic bioactive molecules that selectively modulate protein-protein interactions or enzymatic activities involved in TGF-b signaling. Examples of such molecules include nanobodies, macrocyclic kinase inhibitors. PROTACs (Proteolysis targeting chimeric molecules) and modulators of the ubiquitin machinery.
As a team we take a multidisciplinary approach including high throughput chemical screens, genetics, (bio)chemistry, cell biology, zebrafish/mouse models and mathematics and bioinformatics.
- The candidate should (expect to) hold a PhD in chemical - or molecular cell biology
- Expertise in biochemistry is essential
- Candidates should be highly motivated with proven research abilities and an excellent publication record
- Willingness and proven ability to work both independently and as part of a team
About the department of Cell & Chemical Biology : It is equipped with state-of-art facilities for molecular and cell biology, microscopy, chemistry, proteomics, genetics and protein chemistry.
- Zhang L. et al. TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Mol Cell. 2013 51:559-72;
- Xie F et al. FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis. Nat Commun. 2017 Apr 26;8:15021. doi: 10.1038/ncomms15021;
- Breitkopf-Heinlein K et al. BMP-9 interferes with liver regeneration and promotes liver fibrosis. Gut. 2017 May;66(5):939-954. doi: 10.1136/gutjnl-2016-313314;
- Li Y et al. Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models. Breast Cancer Res. 2015 Feb 25;17:28. doi: 10.1186/s13058-015-0537-8.
Enquiries should be addressed to: Peter ten Dijke (P.ten_Dijke@lumc.nl).
Post-doc Position in TGF-b Signaling and Chemical Biology
Molecular Cell Biology, Leiden University Medical Center, The Netherlands
A Post-Doctoral position is available to study the molecular basis of subverted TGF-b signal transduction in human diseases.
Our group is interested in unravelling mechanisms by which perturbation in signalling of TGF-β family members contribute to diseases. The present focus within our group is on the identification of novel critical regulators (in particular E3 ubiquitin ligases and DUBs) of TGF-β signaling pathways. We use mouse and zebrafish models. Our long term aim is to translate our findings towards the development of novel treatments.
Project description: Misregulation of TGF-b signalling has been implicated in many different diseases, including cancer, fibrosis and cardiovascular diseases. We have performed genetic gain and loss of function genetic and proteomic screens to identify novel druggable regulators of TGF-β pathways. In this project the mechanism of action and importance in disease of these novel regulators will be elucidated. In addition, we will harness the ubiquitin machinery (e.g. using PROTACs) to induce degradation of critical pro-oncogenic factors.
Requirements: We are searching for a highly motivated and experimentally talented scientist with drive to answer important fundamental research questions. Applicants should hold a recent Ph.D. and have a strong background in biochemistry and molecular cell biology and have previous experience in signal transduction or chemical biology. Reporting and publishing the results in high impact scientific journals and at international conferences is expected.
The employment will be for a period of 2 years with possibility for extension. Start date: as soon as possible.
- Zhang Z et al. . Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Nat Commun. 2017 Dec 13;8(1):2116.
- Zhou F et al. USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling. EMBO J. 2017 Jun 1;36(11):1623-1639.
- Zhang L. et al. TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Mol Cell. 2013 51:559-72
- Zhang X et al. Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 2013 32:996-1007.
Please send a cover letter with curriculum vitae, a description of research accomplishments, and contact information of two references to: Peter ten Dijke, Chemical Signaling laboratory, Dept. Cell and Chemical Biology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands; Email: firstname.lastname@example.org.