Education:
BA 1985 Biology - Princeton University, Princeton, NJ
PhD 1992 Neurobiology - Harvard University, Cambridge, Massachusettes
Postdoctoral Research Fellowship:
1992-1994 Harvard Medical School, Boston, Massachusettes
1994-1997 Howard Hughes Medical Institute and Harvard Medical School
Started at USC: 1999
Research Topics: Physiology, Membranes & Transport, Cellular Neurobiology
Research Description
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 thier 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.
Selected Publications
Takashima Y, Daniels RL, Knowlton W, Teng J, Liman ER, McKemy DD. - Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons. - J Neurosci [ 2007 ] Dec 19;27(51):14147-57 . PubMed
Young JM, Waters H, Dong C, Fulle HJ, Liman ER. - Degeneration of the olfactory guanylyl cyclase D gene during primate evolution. - PLoS ONE [ 2007 ] Sep 12;2(9):e884 . PubMed
Zhang Z, Zhao Z, Margolskee R, Liman E. - The transduction channel TRPM5 is gated by intracellular calcium in taste cells. - J Neurosci [ 2007 ] May 23;27(21):5777-86 . PubMed
Liman ER. - TRPM5 and taste transduction. - Handb Exp Pharmacol [ 2007 ] (179):287-98 . PubMed
Liman ER. - Use it or lose it: molecular evolution of sensory signaling in primates. - Pflugers Arch [ 2006 ] Nov;453(2):125-31 . PubMed
Zhang H, Xu Y, Zhang Z, Liman ER, Prestwich GD. - Synthesis and biological activity of phospholipase C-resistant analogues of phosphatidylinositol 4,5-bisphosphate. - J Am Chem Soc [ 2006 ] May 3;128(17):5642-3 . PubMed
Liman ER. - Thermal gating of TRP ion channels: food for thought? - Sci STKE [ 2006 ] Mar 14;2006(326):pe12 . PubMed
Zhang Z, Okawa H, Wang Y, Liman ER. - Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. - J Biol Chem [ 2005 ] Nov 25;280(47):39185-92 . PubMed
Zufall F, Ukhanov K, Lucas P, Liman ER, Leinders-Zufall T. - Neurobiology of TRPC2: from gene to behavior. - Pflugers Arch [ 2005 ] Oct;451(1):61-71 . PubMed
Liu D, Zhang Z, Liman ER. - Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. - J Biol Chem [ 2005 ] May 27;280(21):20691-9 . PubMed
