Joel Yisraeli, PhD

An interview with ICRF-funded researcher Joel Yisraeli, PhD during Lung Cancer Awareness Month in November

Can you briefly describe what you are working on? 

Igf2bp1 is an RNA binding protein associated with many kinds of cancers. It interacts with many oncogenic RNAs, including the RNA encoding the most common oncogene, mutant Kras. By stabilizing these RNAs, Igf2bp1 promotes progression and metastasis of many different kinds of tumors. For example, patients with a mutant Kras and elevated levels of Igf2bp1 have an almost 500% higher risk factor for lung cancer than patients with mutant Kras but low levels of Igf2bp1. Its limited expression in healthy adults makes Igf2bp1 an excellent target for directed therapies. We have found a molecule that inhibits Igf2bp1 and represses the cancer phenotype of lung carcinoma cells. Under the auspices of the work funded by ICRF, we will enhance and calibrate the molecule in mouse models in order to develop a novel targeted therapy for lung and other cancers.  

What are you hoping to achieve by this research? 

The molecule we developed is highly specific for Igf2bp1, and so far, we have found little or no off-target effects. This suggests to us that the molecule could function as what we call a “precision drug” that would be expected to have very few side effects. This drug also has the potential of reducing the chemoresistance often observed to arise with many traditional, but effective, treatments. This drug thus could also be used as an adjuvant therapy that could allow much lower doses of chemotherapy to be much more effective. 

As a “repeat” ICRF grantee, can you tell us about your relationship with ICRF over the years? 

ICRF has played a very important role in my career. I was a recipient of a Career Development Award when I first set up my lab at the Faculty of Medicine of the Hebrew University. Having returned from a post-doctoral fellowship at Harvard in developmental biology, I was interested in understanding how an oocyte is spatially organized and how this contributes to the development of the embryo. Even though the connection to cancer was rather remote, the ICRF understood that this was the sort of basic research that could lead to an understanding of cellular polarity, something often lost when cells become cancerous. The protein that we were able to isolate from frog oocytes turned out to be a member of the Igf2bp family and was highly connected to cancer. Over the years, I was fortunate to receive a number of ICRF awards, and these have helped us explore the role of these RNA binding proteins in development and cancer. 

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