Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA
The Ronai Lab studies signaling networks that are deregulated in cancer in order to understand how to correct them. We focus on pathways that are engaged in the control of RNA translation, splicing and protein homeostasis, which define cancer responsiveness to external and internal stress imposed by harsh microenvironmental conditions (e.g., nutrient deprivation, hypoxia, therapy). Recognizing that these pathways define tumor cell ability to progress, metastasize, withstand therapy or enter dormancy, we expect our studies to pave new roads for cancer therapy.
Members of the lab (from left to right): Regina Kapono, Yongmei Feng, Stefania Tocci, Ben Van Espen, Sachin Verma, Ali Khateb, Marzia Scortegagna, Erez Hasnis, Hyungsoo Kim, Ze'ev Ronai.
We focus on a number of ubiquitin ligases, recognizing their importance in the control of cellular response and adaptation to external and internal stress stimuli, defining tumor cell plasticity which is hallmark of its development, metastasis and resistance phenotypes.
Our studies are guided by data from relevant cancer patient specimens, coupled with advanced bioinformatics, which allow us to predict pathways that are then tested in genetic mouse models and relevant cultures (including spheroid and organoids).
While most of our work is focused on melanoma, ongoing studies addresses critical questions in pancreatic cancer and AML, augmenting earlier studies on prostate and breast cancer.
When applicable, we advance our mechanistic understanding with the development of small molecule inhibitors that may offer novel therapeutic modalities. Among those are our studies with SBI-756, an inhibitor of the translational initiation complex, and with small molecule inhibitors of the ubiquitin ligase Siah2 and the glutamine carrier protein SLC1A5.