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Nabieh Ayoub, PhD

Nabieh Ayoub, PhD

Grant Status
Active

Institution
Technion, Israel Institute of Technology

Grant Type
Project Grant

Project Title
Targeting DNA replication stress to eliminate RBM10-deficient lung adenocarcinoma

Tumor Types

Research Topics
Lung Cancer


About the Investigator:

Dr. Ayoub’s research focuses on identifying new DNA damage responsive proteins and characterizing their role in DNA damage repair and cancer development. He began his scientific career at the Hebrew University where he received a BSc in Biology, an MSc with distinction in Genetics, and then earned his PhD at Hadassah Medical School. He completed his postdoctoral training at the MRC Cancer Cell Unit at the University of Cambridge, UK. He returned to Israel in 2010 and established his lab at the Technion, where he is currently a tenured Associate Professor in the Faculty of Biology. His ultimate goal is to translate his findings into diagnostic and therapeutic tools to defeat cancer and other related diseases.

About the Research:

Lung adenocarcinoma comprises about 40% of all lung cancer cases, the leading cause of cancer deaths worldwide. It is, therefore, imperative to develop novel therapeutic strategies for lung adenocarcinoma patients. Intriguingly, the RBM10 gene, which possesses tumor suppressor activity, is the most mutated gene in this disease, with mutations evident in more than 20% of invasive tumors. This motivated the Ayoub laboratory to ask if mutations in RBM10 might sensitize cells to the absence of other factors. A genetic screen revealed 221 genes that, when inhibited, selectively eradicate lung adenocarcinomas in cells carrying RBM10 mutations. One of these genes is called WEE1, normally a gatekeeper for cell division.

The Ayoub team now proposes to focus on understanding the molecular mechanisms that cause the death of RBM10-deficient lung adenocarcinoma cells in response to WEE1 inhibition, and to determine the efficiency and the efficacy of WEE1 inhibitors in suppressing the growth of RBM10-deficient tumors in mice. Those experiments will establish the preclinical basis for therapeutic targeting of RBM10-deficiency in patients.

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