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Education
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 B.A. Biology, Princeton University, 1/1985
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Ph.D. Neurology, Harvard University, 1/1992
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Description of Research
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Summary Statement of Research Interests
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Second messenger signaling in sensory systems
1. Taste transduction; we use molecular and electrophysiological approaches to understand how taste stimuli are detected and transduced by primary sensory neurons in the tongue.
2. TRP ion channel regulation: we study second messenger regulation of diverse members of this newly identified family of ion channels to understand their contribution to sensory physiology.
3. Pheromone detection; studies of pheromone detection include evolutionary analysis of components of pheromone detection and cloning and functional analysis of proteins involved in pheromone detection.
Cellular signaling forms the fundamental basis for nervous system function and dysfunction. Membrane events, such as the binding of a neurotransmitter to its receptor, are transduced into intracellular signals that regulates membrane potential, transcriptional activity and other cellular functions. Our lab focuses on signaling in the context of sensory neurons whose functions are well understood, such as those in the taste and olfactory systems.
A specific focus of the lab is on ion channels that are members of the transient receptor potential channel (TRP) superfamily. The gene encoding the first member of this family was associated with an aberrant, and transient, response to light in the fruit fly and was later identified as an ion channel that is activated by the phototransduction cascade in this system. At present, 28 vertebrate TRP channels have been identified that fall into several major classes (TRPC, TRPV, TRPM and more). Our work was the first to suggest that a channel in the TRPC family plays a role in vertebrate pheromone transduction (Liman et al, 1999). It is now known that many TRP channels are involved in sensory signaling, including heat and cold reception, auditory transduction and taste transduction.
Projects in the lab are aimed at understanding the second messenger signaling pathways that regulate TRP channels and how these channels contribute to sensory signaling. For example, recent work from our lab has explored the mechanism of activation of an ion channel that is essential for taste transduction (TRPM5). Using patch clamp recording from both heterologously expressed and native TRPM5 channels in taste cells, we were able to show that this channel is directly activated by Ca2+ (Liu and Liman, 2003; Zhang et. al, 2007) supporting the view that taste signaling is mediated by elevation of IP3 and the consequent release of Ca2+ from intracellular stores. We also found that this channel and a structurally related channel TRPM4 are regulated by the membrane phospholipid PIP2 (Liu and Liman, 2003; Zhang et al, 2005). To understand sensory signaling, we combine molecular methods, including cloning of novel genes, generation of antibodies and creation and testing of transgenic mice with patch clamp electrophysiology and Ca+2 imaging.
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Research Keywords
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sensory transduction, ion channels, pheromone, olfactory system, molecular neurobiology, TRP channel, taste, pain
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Research Specialties
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Neurobiology & Computational Neurobiology
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Publications
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Book Chapter
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Liman, E. R., Dulac, C.
(2006).
TRPC2 and pheromone transduction. pp. p.. TRPC2 and pheromone transduction/CRC PRESS.
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Liman, E. R.
(2006).
Ca2+ activated TRPs: TRPM4 and TRPM5. Boca Raton, FL - New York, NY: CRC Press LLC of Taylor and Francis Books.
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Liman, E. R.
(2006).
TRPM5 and taste transduction. Berlin Heidelberg.
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Journal Article
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Zhang, Z., Zhao, Z., Margolskee, R., Liman, E.
(2007).
The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci.
Vol. 27, pp. 5777-5786.
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Young, J. M., Waters, H., Dong, C., Fulle, H. J., Liman, E. R.
(2007).
Degeneration of the Olfactory Guanylyl Cyclase D Gene during Primate Evolution. PLoS ONE 2, e884. Young, J. M., Waters, H., Dong, C., Fulle, H. J., and Liman, E. R..
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Liman, E. R., Zhang, H., Xu, Y., Prestwich, G. D.
(2006).
Synthesis and Biological Activity of Phospholipase C-Resistant Analogues of Phosphatidylinositol 4,5-bisphosphate.
Vol. 128, pp. 5642-5643..
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Liman, E. R.
(2006).
Thermal gating of TRP ion channels: food for thought?. Sci STKE. pp. pe12.
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Liman, E. R.
(2006).
Use it or lose it: molecular evolution of sensory signaling in primates. Pflugers Arch.
Vol. 453, pp. 125-131.
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wang, y., okawa, h., Liman, E. R.
(2005).
Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. Journal of Biological Chemistry.
Vol. 280, pp. p.39185-92.
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liu, D., Liman, E. R.
(2005).
Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involves residues in the S3-S4 and S5-S6 extracellular domains. Journal of Biological Chemistry. pp. p.280(21).
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Liman, E. R., Innan, H.
(2003).
Relaxed selective pressure on an essential component of pheromone transduction in primate evolution. Proc Natl Acad Sci USA.
Vol. 100, pp. 3328-3332.
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Liman, E. R.
(1999).
Liman ER, Corey DP, Dulac C TRP2, a candidate transduction channel for mammalian pheromone sensory signalling. Proc. Natl. Acad. Sci. 96:5791-5796 (1999).
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Honors and Awards
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NIH/NSF Career Development Award, Independent Scientist Award, National Institute on Deafness and Other Communicative Disorders, 2001
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