Molecular Biology of Neural Stem Cells

Neural stem cells are primitive progenitor cells that can both self-renew, and differentiate to various classes of neurons and glia. We are interested in the molecules and mechanisms that control the self-renewal and differentiation of stem cells in both the peripheral and central nervous system. Our approach encompasses microarray and subtractive hybridization to identify novel candidate regulators of stem cell fate, and loss- and gain-of-function genetic manipulations both in vitro and in vivo.

Neural Circuitry of Fear

Fear is a highly conserved emotion with specific behavioral expressions. A great deal has been learned about neural circuits for learned (conditioned) fear, but much less is known about circuits for unlearned (innate or unconditional) fear. We are interested in the relationship between the neural circuits mediating learned and innate fear. We have defined behavioral assays to compare these two types of fear using similar stimuli, and are developing molecular genetic tools to functionally manipulate the underlying neural substrates. An elucidation of neural circuits for fear is a pre-requisite for understanding how genes, drugs and experience act on and modify these circuits, in both normal behavior and in affective disorders such as anxiety and depression.

Molecules and Pathways for Pain

Physical contact with the external world is communicated to the brain by the primary somatosensory system. We have discovered a family of G-protein-coupled receptors, called Mrgs, that mark highly specific subsets of primary sensory neurons in dorsal root ganglia. These neurons project specifically to the skin among all the possible somatic and visceral targets innervated by sensory neurons. Our research combines anatomical, behavioral, biochemical, genetic and physiological approaches (in collaboration with the Simon laboratory at Caltech and the Basbaum laboratory at UCSF) to map and functionally dissect the neural circuitry identified by expression of the Mrgs, and understand its role in coding both pleasant and unpleasant sensory stimuli.

Genes and Neural Circuits for Innate Behaviors in Fruit Flies

Drosophila offers a model genetic system with a complex, interesting behavioral repertoire and a powerful armamentarium of tools for both forward and reverse genetic analysis. We are interested in taking an unbiased genetic approach towards mapping neural circuits involved in innate behaviors in the fly. Together with Seymour Benzer, we have established an assay for an "alarm substance" released by flies when subjected to mechanical stress. We are carrying out both "cell ablation screens," to identify neurons required for this behavior, and genetic screens to identify genes required for this behavior. Our aim is to make these approaches converge to understand how, where and when genes act to control the development or function of these circuits, and thereby affect behavior.