Cancer cell plasticity and trans-differentiation therapy lab
Principle investigator - Dana Ishay-Ronen, MD PhD
E-mail: Dana.IshayRonen@sheba.health.gov.il
Research associate – Rakefet Ruth Ben-Yishay, Ph.D
E-mail: RakefetRuth.BenYishay@sheba.health.gov.il
Lab Technician - Sheli Arbili Yarhi, B.Sc
E-mail: Sheli.ArbiliYarhi@sheba.health.gov.il
Physician, Research Project - Dr Eva falah, MD
E-mail: Eva.falah@mail.huji.ac.il
PhD Candidate - Dr Neta Gochman, MD
E-mail: netagochman@gmail.com
Research Assistant, Tamar Eckman
E-mail: Tamar.Eckman@sheba.health.gov.i
The Ishay-Ronen research group - Cancer cell plasticity and trans-differentiation therapy
The Ishay-Ronen group studies cell plasticity and trans-differentiation therapeutic approaches using patient-derived organoids model.
Organoids
Patient-derived organoid cultures are evolving as an in vitro strategy to model development and diseases. The organoid technology allows long-term 3D in vitro expansion of tissue from patients, while retaining key features of the original tissue. Cancer organoids capture inter-patient and intra-tumor heterogeneity for drug sensitivity screening and for analyzing drug-resistance. Thus, organoid cultures can potentially substitute murine models, allowing mechanistic and translational studies with direct clinical implication.
Cancer cell plasticity and trans-differentiation treatment
Cancer cells can transiently change their phenotype during malignant progression. This fundamental biological ability is defined as cancer cell plasticity, which is associated with metastatic cascade and the development of drug-resistance. Hijacking developmental processes as epithelial-to-mesenchymal transition (EMT) enhance cell plasticity. We recently showed that breast cancer cells that have undergone EMT can be terminally differentiated into adipocytes (fat cells) using a combination of two FDA-approved drugs. The conversion of invasive cancer cells into adipocytes repressed primary tumor invasion and metastasis formation in in vivo human models of breast cancer (BC). These results indicate the high promise in utilizing the increased cell plasticity inherent to invasive cancer cells for trans-differentiation therapy.
Our research group aims to reveal mechanisms facilitating cancer cell plasticity by utilizing patient-derived cancer organoids model. Our goal is to crack cancer cell plasticity during metastasis and drug-resistance by a trans-differentiation path.
Cell plasticity in diseased lungs
In collaboration with the pulmonology and thoracic surgery we developed lung-derived airway organoids from a verity of lung diseases. Using confocal microscopy, high-resolution live-imaging and single-cell analysis we aim to uncover differences in epithelial subpopulations and function.
