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Research Interests

• Regulators of G Protein Signaling

Research Synopsis

In my laboratory we study the molecular mechanisms of desensitization. Our primary focus is the regulation of G proteins, which transmit signals from cell surface receptors to intracellular targets. G protein-coupled receptors bind to neurotransmitters (e.g. adrenaline), peptide hormones (e.g. opiods), odors, taste and light. Genetic defects in these pathways can cause a variety of developmental and metabolic disorders, including cancer, obesity, narcolepsy, drug addiction, and resistance to HIV infection.

G proteins are highly conserved and are even found in the simplest eukaryotes, such as the yeast Saccharomyces cerevisiae. We are currently using genetic screens to identify mutants with altered signaling and desensitization properties in yeast. Such mutants are then characterized biochemically, both in yeast and in human cells (using h omologous components). This approach has led to the discovery of a new family of desensitization factors, called RGS proteins (Regulator of G protein signaling). RGS proteins promote G protein inactivation through their ability to accelerate their GTPase activity. Presently we are using (i) genomics approaches to identify new desensitization factors and their homologues in humans, (ii) proteomics approaches such as mass spectrometry to determine how signaling proteins are regulated through post-translational modifications, (iii) as well as computational and systems biology approaches to identify possible new feedback regulatory mechanisms.

Publications

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