Metastases are the direct cause of death of many patients with cancer, but we don't know enough about their biology and don’t know how to stop them from  spreading. These are the key questions that our lab focuses on. In order to answer these questions we combine the unique resources and databases of the Oncology Department together with the most up to date basic research tools 

What are the adaptations cancer cells acquire to metastasize to specific organs?

1. In order to answer this question we embraced a tumor agnostic approach. We analyzed thousands of pancreatic cancer samples from different metastatic sites and revealed mutations characteristic specifically to liver metastases. In breast cancer, we found that a mutation in the estrogen receptor caused breast cancer cells to change direction and instead of metastasizing to the bone, they metastasize preferentially to the liver. These mutations are implemented in sophisticated in vitro and in vivo models, to explore mechanisms employed by the mutated cells to gain growth advantage in the liver. To this purpose we perform multi OMICS analysis and mine patients' data available in our lab.  Preliminary results show that the mutations shift ammonia metabolism to allow the cancer cells utilize liver metabolism to their advantage. The study opens the door to find inhibitors to pathways activated by mutated cells for to prevent the development of liver metastases. Link to breast cancer study Link to articles pancreatic cancer study.
2. We are using a similar approach in order to gain insight into the development of brain metastasis Link to brain metastasis study.

The link between old age and cancer: the hormone Klotho

Age is a main risk factor for cancer, but the mechanisms responsible for this are unclear. Klotho is a longevity hormone and found in the bloodstream naturally. We found that it is a tumor suppressor, and that its injection to mice inhibits pancreatic, breast, ovarian and colon cancer. Importantly, klotho has a beneficial effect on a variety of physiological activities such as glucose and phosphorus homeostasis, suggesting that Klotho could be used as an effective treatment against cancer while normal cells would be protected. In the laboratory we focus on developing Klotho-based therapies and employ a number of approaches:

1. Locating the anti-cancer activity in klotho protein
2. Identification of its receptor in cancer cells
3. Combining klotho activity with CAR-T cells as a treatment for various cancers
4. Generate nano-particles containing klotho protein or mRNA

Our publication in this area