Rodriguez-Bravo Lab, NCI-Designated Sidney Kimmel Cancer Center.

Thomas Jefferson University. Philadelphia, PA, USA

By Rodriguez-Bravo Lab.
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Genome integrity maintenance in Cancer

One intense area of investigation in our Lab is the role in cancer of the cooperation between mitotic proteins and Nuclear Pore complex (NPC) components (nucleoporins;NUPs) and that we previously described to be essential to protect genome stability (Rodriguez-Bravo et all Cell 2014)Using cancer cell models that mimic the aggressive behavior of human tumor samples cohorts (Mohr L et al. JoVE 2017), preclinical 3D cultures and validation in patient tumor samples we are able to assess the clinical relevance of our mechanistic findings

 

Fluorescence microscopy images of DU145 cells untreated (left) or treated (right) with Docetaxel, an anti-mitotic agent that stabilizes microtubules and thus perturbs normal cell division. Magnified images show in detail mitotic cells in control and treated conditions. (Green, tubulin; Red, DNA) (Rodriguez-Bravo Lab images).

Our research focuses on the study of genome integrity maintenance pathways and their role in cancer. The laboratory is particularly interested in understanding mechanistically the roads leading to chromosomal instability and aneuploidy in human cells and deciphering the consequences for cancer initiation, progression and tumor cells’ therapeutic responses.

To address this, we analyze cell cycle checkpoint responses in non-tumor and tumor cell models and preclinical models through a multidisciplinary approach that combines molecular biology, cell biology, genetics computational analysis and patient tissue sample validation.

 

To study real time cell division and cancer cell responses and survival to standard chemotherapy, such as anti-mitotic agents called taxanes, we monitor cells via high resolution fluorescence microscopy analysis and single-cell live imaging (Figure 1). Our ultimate goal is to understand better fundamental cell division mechanisms in cancer cells to determine novel and more specific targetable pathways in cancer.

Control
Docetaxel