Systems Pharmacology of Epithelial-Mesenchymal Transition (EMT)

Epithelial-Mesenchymal Transition (EMT) is an extensive cellular reprogramming by which, invasive cancer cells of epithelial origin dare to break their commitments in adhering to their neighboring cells and emulate many features of mesenchymal cells. Through this switch, the EMT-undergoing cells would be enabled to confront with the microenvironmental barriers ahead of their transition from the primary tumor site into the blood and form subsequent secondary out-growth.

Owing to the complexity of factors leading to this process, conquering EMT at the clinical stages requires systems-level identification of druggable targets to be shot by drugs. In our lab, we employ Omics -driven insights to formulate a co-drugging regimen and hit the Achilles’ heel of EMT in metastatic cancers. The project is partly funded by Pasteur Institute of Iran (IPI-867) and National Cancer Research Network.

News

The abstract entitled: “Stromal cell secretome reveals the mechanism underlying acquired doxorubicin resistance: a systems pharmacology approach” is due to POSTER presentation in the “The 2nd Interdisciplinary Signalling Workshop” to be held in Visegrád, Hungary on 17-21 July 2017.
The abstract entitled: “Repurposing approved drugs to inhibit epithelial-mesenchymal transition in cancer; A systems pharmacology approach” is due to POSTER presentation in the “EACR-AACR-SIC Special Conference 2017: The Challenges of Optimising Immuno and Targeted Therapies; From Cancer Biology to the Clinic” to be held in Florence, Italy on 24 – 27 June 2017.

Workflow

Generation of Drug-Target Network from DrugBank database:

Generation of in-vitro inducible EMT models by cancer cells co-culture with stromal cells:

Identification and validation of combinatorial target sets to hit EMT by drugs:

Partners

Mohieddin Jafari, Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Farnaz Barneh, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Amir Reza Aref, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.

Mona Salimi, Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.

Mehdi Mirzaie, Department of Applied Mathematics, Faculty of Mathematical Sciences, Tarbiat Modares University, Tehran, Iran.

Presentations

  • “Stromal cell secretome reveals the mechanism underlying acquired doxorubicin resistance: a systems pharmacology approach”, Visegrád, Hungary, 2017.

  • “Data completion: an important determinant for successful integration of drug-target and disease networks”, Annual conference of Systems Biology, Masstricht, Netherlands, 2014.

  • “Repositioning FDA-Approved Drugs for Modulation of Cell-Death; Perspectives from Systems Pharmacology”, the 4th International congress for molecular technology and drug design, Tehran, Iran, 2014.