教育

Ph.D.
路易斯安那州立大学,1993年

兴趣范围

Research Interests

腺苷循环酶调节的机理

Research Information

腺苷循环酶调节的机理

intrac酶腺苷酸环化酶合成ellular second messenger cyclic AMP, which plays a key role in functions ranging from control of heart rate and force of contraction to learning and memory or regulation of pain responses. Many hormones and drugs mediate their actions by binding to G protein-coupled receptors that regulate cAMP production. Our laboratory is using structural, biochemical, live-cell imaging, and molecular biology techniques to understand the complex regulation of adenylyl cyclase by heterotrimeric GTP-binding proteins, kinases and other interacting proteins.

Another major question in the laboratory is how the fidelity of signaling is maintained within a cell. Cyclic AMP is a small diffusible molecule, yet many hormones stimulate cAMP production but elicit different biological responses. We are examining how localization of adenylyl cyclase to specific complexes within the membrane plays a role in cellular signaling. We have discovered that specific anchoring proteins of cAMP-dependent kinase (AKAPs) recruit adenylyl cyclase as well as other regulatory molecules. These signaling complexes have important roles within dorsal root ganglia to control pain responses and also function in the heart to control contractile events. We are currently using biochemical and functional studies in DRG neurons and heart to further define the nature of adenylyl cyclase complexes and to understand how specificity of signaling is generated and maintained under physiological and pathophysiological conditions.

实验室网站:www.Dessauer-Lab.com

Publications

Publication Information

  • Baldwin TA, Li Y, Brand CS, Watts VJ andDessauer CW.(2019)。对9型人腺苷酸环化酶的调节特性的见解。莫尔·普拉姆(Mol Pharm),95:349-360。
  • Odem MA, Bavencoffe AG, Cassidy RM, Lopez ER, Tian J,Dessauer CW, Walters ET. (2018). Isolated Nociceptors Reveal Multiple Specializations for Generating Irregular Ongoing Activity Associated with Ongoing Pain.,159:2347-2362。
  • Gemma N, Cordomí A, Casadó-Anguera V, Moreno E, Cai NS, Cortés A, Canela EI,Dessauer CW,CasadóV,Pardo L,LluísC和FerréS。(2018)。受体异构体和腺苷酸周期酶的功能性预偶联复合物。Nature Communications,9(1):1242。
  • Baldwin TA andDessauer CW。(2018). Function of Adenylyl Cyclase in Heart: the AKAP Connection.J Cardiovasc Dev Dis5(1), 2.
  • Luo J,Bavencoffe A,Yang P,Feng J,Yin S,Qian A,Yu W,Liu S,Gong X,Cai T,Walters ET,Dessauer CW, and Hu H. (2018). Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain.J Neuroscience38(2):474-483.
  • Li Y,Baldwin TA,Wang Y,Brand CS和Dessauer CW。(2017)。9型腺苷酸环化酶的缺失会触发舒张功能障碍和热休克蛋白20的磷酸化降低。科学报告,7(1):5522。
  • Dessauer CW,Watts VJ,Ostrom RS,Conti M,Dove S和Seifert R.(2017)。IUPHAR:哺乳动物腺苷循环酶:从结构到小分子调节剂。Pharmacological Reviews69(2):93-139.
  • Dessauer,CW。(2017)。Shining a Light on GPCR Complexes.J Biol Chem,292(34):14290-14291.
  • Brust TF, Alongkronrusmee D, Soto-Velasquez M, Baldwin TA, Ye Z, Dai M,Dessauer CW, van Rijn RM, Watts VJ. (2017). A small molecule inhibitor of type 1 adenylyl cyclase activity as a non-opioid analgesic agent.Sci Signaling,10(467),EAAH6381。
  • Bavencoffe A, Li Y, Wu Z, Qang Y, Herrera J, Kennedy EJ, Walters ET, andDessauer CW.(2016)。脊髓损伤后原代伤害感受器的持续电活动通过脚手架腺苷酸环化酶和蛋白激酶A的持续性,并与腺苷酸环化酶调节改变有关。J Neuroscience,36(5):1660-8。
  • Brand CS,Sadana R,Malik S,Smrcka AV,Dessauer CW。(2015)。Adenylyl Cyclase 5 Regulation by Gβγ Involves Isoform Specific Use of Multiple Interaction Sites.莫尔·普拉姆(Mol Pharm), 88(4):758-67.
  • Xie K,Masuho I,Shih CC,Cao Y,Sasaki K,Lai CW,Han PL,UEDA H,Dessauer CW,Ehrlich Me,Xu B,Willardson BM和Martemyanov KA。(2015)。纹状体神经元中稳定的G蛋白效应器:组装机制和在神经递质信号传导中的作用。Elife, 10.7554/eLife.10451.
  • 李Y和Dessauer CW:鉴定腺苷酸环化酶与A-激酶锚定蛋白的复合物。(2015)。在X. Cheng Editor中,循环核苷酸信号传导。CRC Press,Taylor and Francis Company,Boca Raton,FL。ISBN:978-1-4822-3556-2。
  • Dvir M, Strulovich R, Sachyani D, Cohen IB, Haitin Y,Dessauer CW, Pongs O, Kass RS, Hirsch J, and Attali B. (2014). Long QT mutations disrupt IKS regulation by PKA and PIP2 at the same KCNQ1 helix C-KCNE1 interface.J. Cell Sci。,127:3943-55。
  • Kahanovitch U, Tsemakhovich V, Berlin S, Rubinstein M, Styr B, Castel R, Peleg S, Tabak G,Dessauer CW, Ivanina T, and Dascal N. (2014). Recruitment of Gβγ controls the basal activity of GIRK channels: crucial role of distal C-terminus of GIRK1.生理学592: 5373-90.
  • tselnicker if,tsemakhovich v,rishal i,Dessauer CW和Dascal N.(2014)。G蛋白的双重调控和G蛋白激活的K+锂通道。Proc。纳特。学院Sci。,111:5018-23。
  • Brand CS, Hocker HJ, Gorfe AA, Cavasotto CN,Dessauer CW。(2013)。Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds.J Pharmacol Exp Ther.347(2): 265-75.
  • Conley JM,品牌CS,Bogard AS,Pratt EPS,Xu R,Hockerman GH,Ostrom R,Dessauer CW, and Watts VJ. (2013). Development of a high-throughput screening paradigm for the discovery of small molecule modulators of adenylyl cyclase: Identification of an adenylyl cyclase 2 inhibitor.JPET347(2):276-87。
  • Efendiev R, Bavencoffe A, Hu, H, Zhu MX,Dessauer CW.(2013)。脚手架的-Kinase Anchoring Protein enhances functional coupling between adenylyl cyclase and TRPV1 channel.J Biol Chem。,288,3929-3937。
  • 斯科特JD,Dessauer CW,Tasken K.(2013)。从混乱中创建顺序:通过激酶锚定的细胞调节。年度Rev Pharm and Tox。,53:187-210。
  • Dessauer CWand Sadana R. (2012) Adenylyl Cyclase.Encyclopedia of Signaling Molecules, Springer publishing, pp 59-66.
  • Efendiev R,Bavencoffe A,Hu H,Zhu MX,Dessauer CW。(2012) Scaffolding by A-Kinase Anchoring Protein Enhances Functional Coupling between Adenylyl Cyclase and TRPV1 Channel.J Biol Chem.,12月21日。
  • Ejendal KFK,Dessauer CW,Hebert TE和Watts VJ。(2012)多巴胺D2受体介导的AC5异源敏化需要信号组组装。J Signal Trans, 2012: 210324-30.
  • Li Y,Chen L,Kass RS和Dessauer CW.(2012)A-Kinase锚定蛋白Yotiao促进了9型腺苷酸环化酶和心脏中IKS钾通道之间的复合形成。J. Biol. Chem.,287(35):29315-29824。
  • 斯科特JD,Dessauer CW, and Tasken K. (2012) Creating order from chaos: Cellular regulation by kinase anchoring.Ann Rev Pharm & Tox,53:187-210。(Epub 2012年10月8日)。
  • Xie K, Masuho I, Brand C,Dessauer CW,and Martemyanov K.(2012)纹状体G蛋白调节剂RGS9-2/Gβ5控制5型腺苷酸环化酶的致敏和时间信号传导。Science Signaling, 5(239):ra63.
  • Pulliainen AT,Pieles K,Brand CS,Hauert B,BöhmA,Quebatte M,WEPF A,Gstaiger M,Aebersold R,Dessauer CW,和Dehio C.(2012)细菌效应子结合宿主细胞腺苷酸环化酶与增强GαS依赖性cAMP的产生。Proc。纳特。学院Sci.109:9581-9586。
  • Berlin S, Tsemakhovich VA, Castel R, Ivanina T,Dessauer CW, Keren-Raifman T, Dascal N. (2011) Two Distinct Aspects of Coupling between Gαi and GIRK Channel Revealed by Fluorescently-Labeled Gαi3 Subunits.J Biol Chem286,33223-33235。
  • Efendiev r和Dessauer CW。(2011) AKAPs and Adenylyl Cyclase in Cardiovascular Physiology and Pathology.J Cardio Pharm58,339-344。
  • Efendiev R,Samelson BK,Nguyen BT,Phatarpekar PV,Baameur F,Scott JD,Dessauer CW。(2010)AKAP79与多个腺苷酸环化酶(AC)同工型和支架AC 5和6与AMPA受体相互作用。J Biol Chem.,285(19):14450-8。
  • Vayttaden SJ, Friedman J, Tran TM, Rich TC,Dessauer CW和Clark RB。(2010)。GRK介导的β2AR调控的定量模型。PLOS计算生物学6,E1000647。
  • Sadana R,Dascal N和Dessauer,CW。N-terminus of Type 5 Adenylyl Cyclase Scaffolds Gs Heterotrimer.莫尔·普拉姆(Mol Pharm),76,1256-1264,2009。
  • Sadana R andDessauer CW。(2009)。G蛋白调节的腺苷环酶同工型的生理作用:敲除和过表达研究的见解。神经信号, 17, 5-22.
  • Dessauer CW。(2009)。Adenylyl Cyclase – AKAP Complexes: The Next Dimension in cAMP Signaling.莫尔·普拉姆(Mol Pharm), 76:935-941.
  • Kapiloff MA, Piggott LA, Sadana R, Li J, Heredia LA, Henson E, Efendiev R, andDessauer CW.(2009)。腺苷酸环酶-makapβ信号传导复合物保持心肌细胞的基础cAMP水平。J Biol Chem.,284:23540-23546。
  • Piggott LA,Bauman A,Scott JD和Dessauer CW。(2008). The A-Kinase Anchoring Protein Yotiao Binds and Regulates Adenylyl Cyclase in Brain.Proc Natl Acad Sci,105:13835-13840。
  • Bauman A,Soughayer J,Nguyen BT,Willoughby D,Wong W,Hoshi N,Langeberg LK,Cooper DMF,Dessauer CW, and Scott JD. (2006) Dynamic regulation of cAMP synthesis through anchored PKA/Adenylyl cyclase V/VI complexes.分子细胞,23(6):925-931。
  • Nguyen BT, andDessauer CW。(2005). Relaxin Stimulates PKCζ Translocation via PI3K to Increase cAMP Production in THP-1 Cells.Mol Endo,19:1012-1023。
  • Chen-Goodspeed M, Lukan AN, andDessauer CW。(2005). Modeling of Gαi and Gαs Regulation by Human Types V and VI Adenylyl Cyclase.J Biol Chem。,280:1808-1816。
  • Salim S, Sinnarajah S, Kehrl JH, andDessauer CW.(2003)。Identification of RGS2 and Type V Adenylyl Cyclase Interaction Sites.J Biol Chem278:15842 - 15849。
  • Nguyen BT,Yang L,Sanborn BM和Dessauer CW。(2003)。磷酸肌醇3-激酶活性是通过松弛蛋白对循环AMP进行双相刺激所必需的。Mol Endocrinol17(6): 1075-84.
  • Dessauer CW,Chen-Goodspeed M和Chen J.(2002)。GI介导的V型腺苷酸环化酶的抑制机理。J Biol Chem277: 28823-28829.
  • Sinnarajah S,Dessauer CW, Srikumar D, Chen J, Yuen J, Yilman S, Dennis JC, Morrison EE, Vodyanoy V, and Kehrl JH. (2001). RGS2 Regulates Signal Transduction in Olfactory Neurons by Attenuating Adenylyl Cyclase III Activation.Nature409:1051-1055。