Merritt Maduke

Honors and Awards

• Cranefield Award, Society of General Physiologists (2008)
• Scientist Development Award, American Heart Association (2004-2007)
• Faculty Scholar, Esther Ehrman Lazard (2003-2005)

Professional Education

• Ph.D., UCSD Chemistry & Biochemistry (1995)
• B.S., Wheaton College Chemistry (1989)

Postdoctoral Advisees

• Carl Jonas Arnold Almqvist, Michelle Dupre, Shelley Elvington

Graduate & Fellowship Program Affiliations

• Biophysics
• Molecular and Cellular Physiology
• Neurosciences

Web Site Links

• Personal Web site

Research Interests

CLC chloride-transport proteins are expressed ubiquitously. Defects in these proteins are responsible for human diseases of kidney and bone, for disorders of blood-pressure regulation, and for epilepsy.

Research in the Maduke lab involves a combination of electrophysiological, structural, and biochemical methods. In addition to ongoing projects, new directions include 1) using NMR to probe ion binding and conformational changes 2) designing and implementing high-throughput fluorescence-based assays to discover inhibitors and activators of the CLCs and 3) probing mechanisms of how mutations in ClC-2 lead to epilepsy.

Publications

• Review. Proton-coupled gating in chloride channels. Lísal J,  Maduke M.  Philos Trans R Soc Lond B Biol Sci.  2009; 364 (1514): 181-7
• Substrate-driven conformational changes in ClC-ec1 observed by fluorine NMR. Elvington SM,  Liu CW, Maduke MC.  EMBO J.  2009; 28 (20): 3090-102
• Thinking outside the crystal: Complementary approaches for examining transporter conformational change. Elvington SM,  Maduke M.  Channels (Austin).  2008; 2 (5)
• A cytoplasmic domain mutation in ClC-Kb affects long-distance communication across the membrane. Martinez GQ,  Maduke M.  PLoS One.  2008; 3 (7): e2746
• Discovery of potent CLC chloride channel inhibitors. Matulef K,  Howery AE, Tan L, Kobertz WR, Du Bois J, Maduke M.  ACS Chem Biol.  2008; 3 (7): 419-28
• The ClC-0 chloride channel is a 'broken' Cl-/H+ antiporter. Lísal J,  Maduke M.  Nat Struct Mol Biol.  2008; 15 (8): 805-10
• The CLC 'chloride channel' family: revelations from prokaryotes. Matulef K,  Maduke M.  Mol Membr Biol.  2007 Sep-Dec; 24 (5-6): 342-50
• The mechanism of fast-gate opening in ClC-0. Engh AM,  Faraldo-Gómez JD, Maduke M.  J Gen Physiol.  2007; 130 (4): 335-49
• The role of a conserved lysine in chloride- and voltage-dependent ClC-0 fast gating. Engh AM,  Faraldo-Gómez JD, Maduke M.  J Gen Physiol.  2007; 130 (4): 351-63
• Side-dependent inhibition of a prokaryotic ClC by DIDS. Matulef K,  Maduke M.  Biophys J.  2005; 89 (3): 1721-30
• Cysteine accessibility in ClC-0 supports conservation of the ClC intracellular vestibule. Engh AM,  Maduke M.  J Gen Physiol.  2005; 125 (6): 601-17
• The poststructural festivities begin. Maduke M,  Mindell JA.  Neuron.  2003; 38 (1): 1-3
• Projection structure of a ClC-type chloride channel at 6.5 A resolution. Mindell JA,  Maduke M, Miller C, Grigorieff N.  Nature.  2001; 409 (6817): 219-23
• A decade of CLC chloride channels: structure, mechanism, and many unsettled questions. Maduke M,  Miller C, Mindell JA.  Annu Rev Biophys Biomol Struct.  2000; 29 411-38
• High-level expression, functional reconstitution, and quaternary structure of a prokaryotic ClC-type chloride channel. Maduke M,  Pheasant DJ, Miller C.  J Gen Physiol.  1999; 114 (5): 713-22
• Formation of CLC-0 chloride channels from separated transmembrane and cytoplasmic domains. Maduke M,  Williams C, Miller C.  Biochemistry.  1998; 37 (5): 1315-21
• Import of a mitochondrial presequence into P. denitrificans. Insight into the evolution of protein transport. Roise D,  Maduke M.  FEBS Lett.  1994; 337 (1): 9-13
• Import of a mitochondrial presequence into protein-free phospholipid vesicles. Maduke M,  Roise D.  Science.  1993; 260 (5106): 364-7