In 2015 the Ronai Lab in La Jolla CA, expanded and has setup a sister lab at the Technion - Israel Institute of Technology, Haifa, Israel. Both laboratories study, in concert, signaling networks that are deregulated in cancer, in an effort to understand how it may be possible to correct them.
Our projects concern cellular signaling pathways that are engaged in control of normal homeostasis and the response to external and internal stress imposed by harsh microenvironmental conditions (nutrient deprivation, hyopxia, therapy).
Members of the La Jolla Lab (left to right)
Yan Li, Hyungsoo Kim, Yann Chelli, Marzia Scortegagna, Yongmei Feng, Giusy Claps, Hiro Tamiya, Morgan Gregoy
Our studies focus on cellular pathways such as the unfolded protein response, mitochondrial biogenesis, protein translation control - that undelie tumor cell ability to adjust to harsh conditions and evolve as a dormant, resistant or metastatic niche. Such plasticity poses major obstacle in achieving durable response to therapy.
Recognizing that epigenetic changes are dictated by environmental stimuli and complement the genetic events in cancer, we have focused our attention on ubiquitin ligases that play key role in cellular response and adaptation of cancer cells, enabling what we now recognize as tumor cell plasticity.
Among key pathways we focus on are ubiquitin ligases (Siah1/2, RNF5, RNF125) and stress induced signaling (JNK/PDK1/ATF2) that define tumor cell adaptation to stress and determine their ability to adjust by means of resistance to therapy or metstatic capacity.
We have been studying these processes in melanoma, prostate and breast cancer using cell cultures, genetic models (GEMM) and have validated our findings using patient tumor samples.
Our understanding of epigenetic processes that underlie tumor cell plasticity is expected to pave new roads in defining tomorrows therapies. To this end we have developed SBI-0640756, a small molecule that disrupts the translation initiation machinary, enabling to overcome therapy-resistant melanoma.