MERRITT C. MADUKE, Ph.D. ACADEMIC HISTORY Education Stanford University School of Medicine Department of Molecular and Cellular Physiology B155 Beckman Center 279 Campus Drive Stanford, CA 94305-5345 1989 B.S. with Honors (Chemistry), Wheaton College, Wheaton, IL 1995 Ph.D., Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA Postdoctoral Training 1995 2001 Postdoctoral Fellowship, Ion Channels, Brandeis University Dept of Biochemistry and HHMI (laboratory of Dr. Christopher Miller) Academic Appointments: 2001 2009 Assistant Professor of Molecular & Cellular Physiology Stanford University, Stanford, CA 2009 present Associate Professor of Molecular & Cellular Physiology Stanford University, Stanford, CA Scholarships and Honors 1989 Summa cum laude in Chemistry, Wheaton College 2003 Esther Ehrman Lazard Faculty Scholar 2004 American Heart Association Scientist Development Award 2008 Cranefield Award (Society of General Physiologists) 2009 Stanford Faculty Fellow 2010 Stanford SPARK Scholar PUBLIC AND PROFESSIONAL SERVICE Journal Referee 2001 to present Biochemistry, Biophysical Journal, EMBO Journal, Journal of Cell Biology, Journal of General Physiology, Journal of Neuroscience, Nature Communications, Nature Structural & Molecular Biology, Neuron, PNAS, Science, Structure Grant Referee 2005 NIH Special Study Section for Membrane Proteins RFA 2008, 2010 American Heart Association, Western States Peer Review Committee 2011 Co-Chair, American Heart Association Unified Peer Review: Basic Cell Proteins & Crystallography 2012 present Chair, American Heart Association Unified Peer Review: Basic Cell Proteins & Crystallography Merritt C. Maduke Page 1 of 5
Service to Professional Organizations 2007 2010 Councilor, Society of General Physiologists 2009 2012 Committee for Professional Opportunities for Women (CPOW), Biophysical Society 2010 present Editorial Board, Journal of General Physiology 2010 Volunteer Judge, California State Science Fair 2010 Chair, Ion Channels Gordon Research Conference 2010 present Volunteer, Science is Elementary (Mountain View) 2012 2015 Councilor, Biophysical Society 2012 Nominating Committee, Biophysical Society 2013 co-chair, Society of General Physiologists Annual Meeting 2013 present Associate Editor, Journal of General Physiology University Committees and Service 2001 present MSTP Admissions Committee 2001 present Fourteen Thesis Committees (Biophysics, Biochemistry, Chemical Engineering, Chemistry, Molecular & Cellular Physiology, Neurosciences, Structural Biology) 2001 present Supervised thirteen undergraduate research students 2006 2007 Molecular & Cellular Physiology Faculty Search Committee 2007 present Biophysics Admissions Committee 2007 present Molecular & Cellular Physiology Admissions Committee 2008, 2012 present Freshman Advisor 2010 present Program Committee for Stanford Neurosciences 2010 present Neuroscience Student Advisor 2012 present Biophysics Executive Committee 2012 present Chair, Provost s Advisory Committee on Postdoctoral Affairs Professional Societies 1990 present American Chemical Society 1990 present American Association for the Advancement of Science 1995 present Biophysical Society 2003 present Society of General Physiologists 2007 present American Heart Association 2008 present American Physiological Society BIBLIOGRAPHY Peer-reviewed Research Articles 1. Maduke, M., and Roise, D. Import of a mitochondrial presequence into protein-free phospholipid vesicles. Science 260, 364-367, 1993. 2. Roise, D., and Maduke, M. Import of a mitochondrial presequence into P. denitrificans. Insight into the evolution of protein transport. Febs Letters 337, 9-13, 1994. 3. Maduke, M., Williams, C., and Miller, C. Formation of CLC-0 chloride channels from separated transmembrane and cytoplasmic domains. Biochemistry 37, 1315-1321, 1998. 4. Maduke, M., Pheasant, D. J., and Miller, C. High-level expression, functional reconstitution, and quaternary structure of a prokaryotic ClC-type chloride channel. J. Gen. Physiol. 114, 713-722, 1999. Merritt C. Maduke Page 2 of 5
5. Mindell, J.A., Maduke, M., Miller, C., and Grigorieff, N. Projection structure of a ClC-type Cl - channel at 6.5 Å resolution. Nature 409, 219-223, 2001. 6. Engh, A.M. and Maduke, M. Cysteine accessibility in ClC-0 supports conservation of the ClC intracellular vestibule. J. Gen. Physiol. 125, 601-17, 2005. 7. Matulef, K. and Maduke, M. Side-dependent inhibition of a prokaryotic ClC by DIDS. Biophys. J. 89, 1721-30, 2005. 8. Engh, A.M., Farraldo-Gomez, J., and Maduke, M. The mechanism of fast-gate opening in ClC-0. J. Gen. Physiol. 130, 335-349, 2007. 9. Engh, A.M., Farraldo-Gomez, J., and Maduke, M. The role of K149 in chloride and voltage dependent gating of ClC-0. J. Gen. Physiol. 130, 351-360, 2007. 10. Matulef, K., Howery, A.E., Tan, L., Kobertz, W.R., Du Bois, J., and Maduke, M. Discovery of Potent CLC Chloride Channel Inhibitors. ACS Chem. Biol. 3, 419-428, 2008. 11. Lisal, J. and Maduke, M. The ClC-0 chloride channel is a broken Cl - /H + antiporter Nature Struct. Mol. Biol. 15, 805-810, 2008. 12. Martinez, G.Q. and Maduke, M. A cytoplasmic domain mutation in ClC-Kb affects longdistance communication across the membrane. PLoS ONE 3, e2746, 2008. 13. Elvington, S.E., Liu, C. W., and Maduke, M. Substrate-driven conformational changes in ClC-ec1 observed by fluorine NMR. EMBO J, 28(20), 3090-310, 2009. 14. Howery, A.E., Elvington, S.M., Abraham, S.J., Choi, K.H., Dworschak-Simpson, S., Phillips, S., Ryan, C.M., Sanford, R.L., Almqvist, J., Tran, K., Chew, T.A., Zachariae, U., Andersen, O.S., Whitelegge, J.P., Matulef, K., Du Bois, J. & Maduke, M. A designed inhibitor of a CLC antiporter blocks function through a unique binding mode. Chem. Biol., 19(11), 1460-1470, 2012. 15. Prieto, M.L., Oralkan, Ö, Khuri-Yakub, B.T., and Maduke, M.C. Dynamic response of model lipid membranes to ultrasonic radiation force. PLoS ONE 8, e77115, 2013. PMID:24194863 Review Articles, Commentaries, and Reports 1. Maduke, M., Miller, C., and Mindell, J.A. A decade of ClC chloride channels: structure, mechanism, and many unsettled questions. Ann. Rev. Biophys. Biomol. Struct. 29, 411-438, 2000. 2. Mindell, J.A., Maduke, M. ClC chloride channels. Genome Biology 2(2):REVIEWS3003, 2001. 3. Maduke, M., & Mindell, J. A. The poststructural festivities begin Neuron 38: 1-3, 2003. 4. Matulef, K. and Maduke, M. The CLC Chloride Channel Family: Revelations from Prokaryotes. Molecular Membrane Biology. 24, 342-350, 2005. 5. Elvington, S.E. and Maduke, M. Thinking outside the crystal: Complementary approaches for examining transporter conformational change Channels, 2(5) Epub ahead of print, 2008. 6. Holmqvist, M. and Maduke, M. Meeting Report: Ion Channel Targets Select Biosciences Fourth Annual Conference, IDrugs, 11:795-798, 2008. 7. Lisal, J. and Maduke, M. Proton-coupled gating in CLC channels. Philos Trans R Soc Lond B Biol Sci 364:181-187, 2009. Merritt C. Maduke Page 3 of 5
8. Mindell, J.A. and Maduke, M. Chloride Channels and Transporters. The Encyclopedia of Neuroscience. 9. Maduke, M.C. and Reimver, R.J. Biochemistry to the resuce: a ClC-2 auxiliary subunit provides a tangible link to leukodystrophy. Neuron 73: 855-7, 2012. 10. Denton, J.S., Pao, A.C., and Maduke, M. Invited Review Novel Diuretic Targets. Am J Physiol Renal Physiol. 305(7): F931-42, 2013. Book Chapters 1. Maduke, M., and Roise, D. Structure and function of mitochondrial presequences. In Membrane Protein Transport, vol. 3, S. S. Rothman, ed. (Greenwich, CT: JAI Press), pp. 49-79, 1996 ONGOING RESEARCH SUPPORT Stanford SPARK Award Maduke (PI) 02/01/10- present Development of a New Class of Aquaretics for the Treatment of Hyponatremia This award provides seed money to test CLC-Ka inhibitors in animals in order to develop eventual therapies for the hyponatremia that occurs in heart failure and other diseases. Drs. Justin Du Bois (Chemistry) and Alan Pao (Medicine) are collaborators on this work. NSF MCB 1021472 Maduke (PI) 07/01/10 06/30/14 Probing Conformational Change in a Cl - /H + Antiporter of known Structure The goal of this project is to use 19 F NMR to examine conformational changes in CLC-ec1. NIH PAR-07-412 Perozo (PI) 08/01/10-07/31/15 Membrane Protein Structural Dynamics Consortium The Membrane Protein Structural Dynamics Consortium is organized around multidisciplinary project teams and Core Facilities focused on elucidating the relationship between structure, dynamics and function in a variety of membrane proteins. The resources developed by the Core Facilities are being made available to the broader community. I lead a project within the Consortium to develop studies of CLC structural dynamics in collaboration with Drs. Emad Tajkhorshid (University of Illlinois) and Hassane Mchaourab (Vanderbilt University). Role: Co-PI NIH 1 R21 NS076948 Maduke (PI) 09/01/11 04/30/14 The mechanistic basis of non-invasive deep brain stimulation by ultrasound. This project involves investigating the molecular basis for activation of membranes and ion channels by ultrasound. The results will provide a quantitative framework for developing focused ultrasound as a non-invasive tool for experimental and therapeutic deep brain stimulation. AHA 1GRNT16940072 Maduke (PI) 07/01/13 06/30/15 Developing small-molecule inhibitors of the CLC-Ka chloride channel In this project, we will characterize the inhibitor-binding site of a novel CLC-Ka inhibitor and will use a chemical-design strategy to evolve next-generation inhibitors. Stanford SINTN Reimer (PI) 01/01/13 12/30/15 Development of a novel therapeutic approach to lysosomal storage disorders Merritt C. Maduke Page 4 of 5
The goal of this proposal is to develop a novel method for treating a rare but devastating group of diseases that affect the nervous system Role: Co-PI COMPLETED RESEARCH SUPPORT AHA 027342 Maduke (PI) 07/01/04-06/30/07 Cytoplasmic Domains of CLC Chloride Channels Independent Scientist Award: to conduct structural and functional studies of the conserved cytoplasmic tails found in mammalian CLC chloride channels. AHA 10GRNT3890045 Maduke (PI) 07/01/10-06/30/12 Improving Selectivity of CLC-K Chloride-channel Inhibitors In this project, we used a structure-based approach to develop and characterize specific inhibitors of CLC channels and transporters, for which the pharmacology is poorly developed. The first molecule we developed is the only known inhibitor of the CLC antiporters (Howery et al., 2012). Our identification of the inhibitor binding site is important for development and refinement of next-generation CLC inhibitors. The second molecule we developed, BIM1, has unprecedented specificity for CLC-Ka over CLC-Kb. NIH R01 GM070773-05 Maduke (PI) 08/01/05-10/31/10 Mechanisms of CLC Chloride-transport Proteins The goal of this project is to perform mechanistic studies on CLC-ec1, a chloride-proton antiporter, and CLC-0, a chloride channel, in order to better understand the mechanisms of these proteins as well as the functional relationships between channels and transporters. NIH R01 GM070773-05S1 Maduke (PI) 09/15/09-07/31/10 Mechanisms of CLC Chloride-transport Proteins The goal of this supplement for the parent grant described above is to enhance our progress towards determining the molecular basis for inhibitor binding to CLC-ec1. Merritt C. Maduke Page 5 of 5