Garcia-Marcos Lab

We investigate signal transduction mechanisms with the ultimate goal of elucidating the molecular basis of human diseases and developing novel therapeutic approaches. Our main interest is in heterotrimeric G proteins, which are molecular switches that relay extracellular signals. Heterotrimeric G proteins are primarily activated by G protein-coupled receptors (GPCRs) located at the plasma membrane. However, our lab focuses on a group of cytoplasmic factors that mimic the action of GPCRs by directly activating heterotrimeric G proteins. These non-receptor activators “rewire” signal transduction in different pathological settings, including cancer, fibrosis, insulin resistance and kidney failure, among many others. Our current efforts are focused on (i) identifying the members of this group of non-receptor activators, (ii) defining their role in normal and pathological scenarios, (iii) characterizing the molecular mechanisms by which they are regulated, (iv) understanding the structural basis for their action on G proteins and (v) developing tools to specifically target them. We are exploring this unconventional aspect of G protein signaling in the context of cancer, embryonic development and neurotransmission. Our multidisciplinary approach includes in vitro biochemistry to characterize protein complexes, culture cells and model organisms (yeast, frog embryos) for functional studies and synthetic biology tools to manipulate and monitor signaling with exquisite spatiotemporal resolution.