Dhaka, Ajay, Ph.D. Assistant Professor dhaka@u.washington.edu G-521 616-0018   Our perception of the external world comes from our senses. The sense of touch or somatic sensation consists of the perception of multiple discrete stimuli including temperature, pain, proprioception and discriminative touch. Specialized neurons within the dorsal root ganglia (DRG) and trigeminal ganglia (TG) sense these diverse stimuli via nerve endings that project to the skin, muscles and the organs of the body, and this information is then transmitted to the brain via the spinal cord. Electrophysiological characterization has shown that these neurons receive and relay information from these diverse stimuli at least in part through subclasses of DRG neurons that convey different perceptual modalities. Only in the last decade have the genes involved in the direct gating of sensory modalities begun to be identified. Many of these genes belong to the Transient Receptor Potential (TRP) family of non-selective cation channels. TRPV1 a detector of noxious stimuli (heat, capsaicin, low/high pH), TRPA1 another sensor of noxious stimuli (burning cold and noxious chemical agonists such as mustard oil and formaldehyde) and TRPM8 a sensor of innocuous cool temperature are primarily expressed in subsets of DRG and TG neurons and function as sensory receptors in vivo. While there have been recent advancements, very little is known about how somatosensory neurons become specialized during development and how their neuronal circuitry facilitates their ability to transmit specific environmental cues in the adult. We are interested in understanding the mechanism by which sensory information is coded by the peripheral nervous system, and how specific subclass specificity and neuronal circuit assembly occurs during development. In addition, we are working to identify novel sensory receptors for modalities such as mechanosensation, temperature and nociception. These are fundamental neurobiology themes that are relevant to the study of the many forms of chronic pain, which are debilitating to millions of individuals. In addition, discovering how the simple circuits of the peripheral nervous system assemble and code information output will not only help us understand how we perceive the world around us but may also provide valuable insight into how these processes occur in the more complex circuits of the brain. My lab is taking advantage of the recent identification of molecular markers (TRP channels) that define specific sensory modalities to help further our understanding of sensory perception. To this end, we are using novel tools and techniques that we have developed in combination with mouse genetics, molecular biology, biochemistry and live cell imaging to achieve our goals. Publications: Dhaka A.,* Uzzell V.,* Dubin A., Mathur J., Petrus M., Bandell M., Patapoutian A. TRPV1 senses both acidic and basic pH. J. Neurosci. 29(1), 153-158 (2009). * authors contributed equally to this work Cruz-Orengo L., Dhaka A. , Heuermann RJ., Young TJ., Montana MC., Cavanaugh EJ., Kim D., Story GM. Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1. Mol. Pain. 4:30 (2008). Dhaka A., Earley TJ., Watson J., Patapoutian A. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J. Neurosci. 28(3), 566-75 (2008). Dhaka A., Murray A., Mathur J., Earley T., Petrus M., Patapoutian A. TRPM8 is required for cold sensation in mice. Neuron. 54(3), 371-378 (2007). Dhaka A., Viswanath V., Patapoutian A. Trp ion channels and temperature sensation. Annu Rev Neurosci. 29, 135-61 (2006). Irvin DK., Dhaka A., Hicks C., Weinmaster G., Kornblum HI. Extrinsic and intrinsic factors governing cell fate in cortical progenitor cultures. Dev Neurosci. 25(2-4), 162-72 (2003). Dhaka A., Costa RM., Hu H., Irvin DK., Patel A., Kornblum HI., Silva AJ., O'Dell TJ., Colicelli J. The RAS effector RIN1 modulates the formation of aversive memories. J Neurosci. 23(3), 748-57 (2003). Wang Y., Waldron RT., Dhaka A., Patel A., Riley MM., Rozengurt E., Colicelli J. The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins. Mol Cell Biol. 22(3), 916-26 (2002). Afar DE., Han L., McLaughlin J., Wong S., Dhaka A., Parmar K., Rosenberg N., Witte ON., Colicelli J. Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1. Immunity. 6(6), 773-82 (1997). Han L., Wong D., Dhaka A. , Afar D., White M., Xie W., Herschman H., Witte O., Colicelli J. Protein binding and signaling properties of RIN1 suggest a unique effector function. Proc Natl Acad Sci U S A. 94(10), 4954-9 (1997).