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基础医学系

Cecilia Canessa

履历

    2014-Present Professor of Medicine Tsinghua University

    2008-2014 Professor Cellular and Molecular Physiology and Internal Medicine, Yale University

    2000-2007 Associate Professor Cellular and Molecular Physiology and Internal Medicine, Yale University

    1994-2000 Assistant Professor Cellular and Molecular Physiology and Internal Medicine, Yale University

    1993-1994 Lecturer Physiology & Pharmacology, University of Lausanne, Switzerland.

    1991-1993 Postdoctoral Fellow Physiology & Pharmacology, University of Lausanne, Switzerland.

    1988-1990 Postdoctoral Fellow Nephrology Department, University of Alabama, USA

    1983-1988 Medicine, University of Minnesota, USA

研究领域与方向

I am a professor in the Departments of Cellular and Molecular Physiology and Medicine at Yale University with 20 years of experience as Principal Investigator conducting independent research, training students and postdoctoral fellows, and teaching physiology courses to Ph.D. students and medical students. My area of expertise is in the field of ion channels of the ENaC/Degenerin family specifically, the epithelial sodium channel ENaC that since its cloning turned into a field of research that attracted many investigators and produced hundreds of publications. We also work on ASICs - Acid Sensing Ion Channels in the brain. We investigate the structure, function and regulations of these channels using electrophysiology, molecular biology and animal models.  Since July of 2014, I joined Tsinghua Medical School as a recipient of the 10000 Talent Program.

1. One aspect of our work is to define the biophysical properties of ENaC and ASIC channels and their behavior in tissues. We use electrophysiology together with protein modifications to advance our understanding on how these channels operate. To facilitate structural and dynamic studies, we introduce informative probes or labels that do not perturb channel function. We use amber codon suppression to genetically-encode unnatural amino acids with reactive properties at various targeted positions. This technology enables structure-functional analysis and the identification of residues involved in dynamic changes through channel activation or desensitization.

2. Another major focus in our lab is to create and validate novel methods for precise spatiotemporal control of ASIC activity in selected microcircuits in the brain of living mice. We have developed an optogenetic-based approach for activation of ASIC in vivo and are currently developing a novel genetic channel inhibitor to target selected populations of neurons. 

3. Epithelial sodium transport varies directly with the expression level of ENaC at the cell surface. The number of surface ENaC channels is regulated by ubiquitination of lysine residues that induces degradation by the proteasome. We are investigating how various physiological paradigms trigger alternative post-translational modifications that compete with lysine ubiquitination to increase expression of ENaC. These novel signaling pathways are shedding new light on unexpected mechanisms regulating sodium transport.



学术荣誉与奖励

关键词

代表性论文

1. Li T, Yang Y, Canessa CM (2014) A Method for Activation of Endogenous Acid-sensing Ion Channel 1a (ASIC1a) in the Nervous System with High Spatial and Temporal Precision. J Biol Chem. 289(22):15441-8

2. Li T, Yang Y, Canessa CM (2012) Impact of Recovery from Desensitization on Acid Sensing Ion Channel-1a (ASIC1a) Current and Response to High-frequency Stimulation. J Biol Chem. 287(48):40680-9

3. Li T, Yang Y, Canessa CM (2011) Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1. Nature Commun. 2:399. doi: 10.1038/ncomms1409

4. Li T, Yang Y, Canessa CM (2011) Asp433 in the closing gate of ASIC1 determines stability of the open state without changing properties of the selectivity filter or Ca2+ block. J. Gen. Physiol.137, 289-97

5.  Li T, Yang Y, Canessa CM (2010) Asn-415 in the β11-β12 linker decreases proton-dependent desensitization of ASIC1. J. Biol. Chem. 285, 31285-312919

6.    Li T, Yang S, Canessa CM (2009) Interaction of the aromatics Y72/W288 in the interface of the extracellular and transmembrane domains is essential for proton gating of ASIC. J. Biol. Chem. 284, 4689-4694

7.    Arteaga MF, Coric T, Straub C, Canessa CM (2008) A novel brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons. P.N.A.S. USA 105, 4459-4464

8.  Arteaga MF, Wang L, Ravid T, Hochstrasser M, Canessa CM (2006) An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery. P.N.A.S. USA 103(30):11178-83.

9.    Alvarez de la Rosa D, Zhang P, Shao D, White F, Canessa CM (2002) Functional implications of the localization and activity of acid-sensitive channels in the rat peripheral nervous system. P.N.A.S. USA 99, 2326-31

10.   Stutts MJ, Canessa CM, Olsen JC, Hamrick M, Cohn JA, Rossier BC, Boucher RC (1995) CFTR as a cAMP-dependent regulator of sodium channels. Science. 269(5225):847-50

11.   Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR, Ulick S, Milora RV, Findling JW, Canessa CM, Rossier BC, Lifton RP (1994) Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 79, 407?14

12.  Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, Rossier BC (1994) Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 367(6462):463-7

13. Canessa CM, Horisberger JD, Rossier BC (1993) Epithelial sodium channel related to proteins involved in neurodegeneration. Nature. 361(6411):467-70.


联系方式

Email: ccanessa at mail.tsinghua.edu.cn

Phone: +86-10-62794016

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