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Trainee Spotlight: Daniela Araiza-Olivera, MD, PhD
Although I initially studied to be a physician, my constant quest to learn new things and explore led me to a career in scientific research. During medical school, I had the opportunity to explore the field of Bioenergetics during a rotation with Dr. Salvador Uribe-Carvajal’s at the Universidad Nacional Autónoma de México. I liked my project so much that I pursed my master’s degree, and later, my PhD, in his lab. During this time, I also had the opportunity to learn about cytoskeleton and motor proteins in cancer cells through a collaboration with Dr. Thomas Surrey at the London Research Institute. In 2014, I accepted a postdoc position with Dr. Jon Chernoff at Fox Chase Cancer Center. Since joining the lab my research has combined my training in bioenergetics and cancer where I study the regulation and role of p21-acivated kinases in diseases such as cancer and developmental abnormalities, and the Hippo tumor suppressor pathway. In January 2017, I accepted an Assistant Professor position at the Institute of Chemistry at the UNAM, in México, where I am planning to study the effect of different small molecules in cancer.
Ras proteins are essential components of the signaling networks controlling cellular proliferation, differentiation, or survival. They are related to the Hippo tumor suppressor pathway, which controls organ size, apoptosis, and cell proliferation in animals through the Mammalian Ste20-like kinases 1 and 2 (Mst1/Mst2, respectively). These Mst kinases may self-associate in homodimers or form heterodimers via a C-terminal SARAH domain. Formation of these complexes can regulate Mst kinase activity, and by consequence, the Hippo pathway. Our recent studies showed that activated Hras promotes the formation of Mst1/Mst2 heterodimers and that activation of Erk was required for this event. Furthermore, Mst1/Mst2 heterodimers were much less active as compared to Mst1/Mst1 or Mst2/Mst2 homodimers. From these results, we propose that the formation of Mst heterodimers was required to deactivate the Hippo pathway and to enable transformation by Hras.
Rawat S*, Araiza-Olivera D*, Arias-Romero L.E, Villamar-Cruz O, Prudnikova T.Y, Roder H, Chernoff J. H-ras inhibits the hippo pathway by promoting Mst1/Mst2 heterodimerization. Curr Biol. 2016 Jun 20; 26 (12):1556-63.
Araiza-Olivera D, Chernoff J. Hras helps Hippo heterodimerize to evade tumor suppression. Small GTPases. 2016 Aug 25:1-5.