Our group explores molecular circuitries and biological processes that affect cancer, specifically tumor suppression by p53 and the Hippo pathways.The p53 tumor suppressor gene is the most frequently mutated gene in cancer. When functional, p53 drives a transcriptional program leading to the elimination of transformed cells. In contrast, cancer-associated mutations in p53 not only abolish its anti-tumor activity, but also endow the p53 protein with novel pro-oncogenic functions.
Research in our lab focuses on the involvement of tumor suppressive wild type p53 and oncogenic mutant p53 in biological processes that determine cell fate and modulate the emergence and progression of cancer.
We are also interested in the “Hippo” tumor suppressive pathway. At the core of the Hippo pathway are two kinases, LATS1 and LATS2, which negatively regulate the pathway effectors, YAP and TAZ. YAP and TAZ are transcriptional cofactors that orchestrate physiological and pathological transcriptional programs, positioning “Hippo” as a master controller of tumor growth and metastasis.
In addition to studying the roles of the p53 and Hippo pathways within the cancer cells, we also aim to elucidate the impact of these pathways on the crosstalk between the cancer cells and their microenvironment, with particular focus on the immune system. For instance, recent findings suggest that p53 mutations might render the cancer cells less susceptible to elimination by the immune system. Additionally, mutant p53 is a key player in regulating tumor inflammatory responses, in part by direct crosstalk with NF-kB, a transcription factor that is a master regulator of the immune system.
Some of the methods employed by our lab include fluorescent imaging, bulk and single cell RNA-sequencing, proteomic analyses, and gene manipulation by CRISPR-Cas9 and siRNA. Using in vitro cell cultures, bioinformatics and human clinical modalities, complemented by in vivo mouse models, we integrate state-of-the-art benchwork with clinically relevant patient data.
Are you an independent, creative, enthusiastic and ambitious scientist with the following qualifications?
- Background in molecular and cellular biology
- Enthusiasm to learn, query and examine biological processes
- Critical thinking and desire to challenge the ruling dogma
- Team player, willing to contribute to a friendly working atmosphere
- In return, we offer good opportunities to further promote your scientific career in a strong and positive research environment.
Aspiring postdoctoral researchers should submit their C.V. and a statement of research and career interests, indicating overlap with our lab’s research areas.
Weizmann Institute of Science, Dept. Molecular Cell Biology
Ullmann Building, room 103,