Dean R. Madden
Dean R. Madden

Titles

Principal Investigator
Professor of Biochemistry
Associate Director, Dartmouth Lung Biology Center
A.B., Genetics, Cellular, and Developmental Biology

Education

A.B. Physics, Harvard 1985
Ph.D. Biophysics, Harvard 1992

Programs

Academy of Master Faculty Educators
Molecular and Cellular Biology Graduate Programs
Neuroscience Center at Dartmouth
Quantitative Biomedical Sciences

Email: drm0001@dartmouth.edu

Professional Interests

The goal of our research is to understand the functional characteristics of ion channels and transporters in terms of their molecular structure. Transmembrane electrochemical gradients underpin a wide variety of essential physiological processes, including photosynthesis and respiration, muscle contraction and nerve signalling. Highly specialized ion transporters are responsible for establishing and maintaining these gradients, while ion channels are designed to exploit the gradients by selectively and/or temporarily permeabilizing the membrane in response to external stimuli. We study two different ion channels in the lab: the cystic fibrosis transmembrane conductance regulator (CFTR) and the glutamate receptor ion channel.

Grant Information

NIH/NIAID
NIH/NIDDK
NIH/NIGMS

Courses Taught

Biochemistry 101: Molecular Information in Biological Systems
Genetics 102: Molecular Information in Biological Systems
Biochemistry 110: The Biochemical and Genetic Basis of Medicine

Biography

Dean started teaching math at a summer ‘bootcamp’ for MPP students, and has since taught math, biochemistry, and biophysics in Munich, Heidelberg, Cambridge, and Hanover. He served as Chair of the MCB Graduate Program and has participated in Dartmouth’s Strategic Planning for Graduate Education and the Geisel Curriculum Reform initiative, where he serves as co-chair of the Biomedical Sciences Working Group and a member of the Master’s Degree Task Force. Dean is currently course director for BIOC101 – the MCB first-term core course – and lectures and leads small-group discussions in BIOC110 – the Geisel first-term Biochemistry course.

Mentoring Information

Dean mentors early-career faculty interested in small-group teaching, graduate education, and research at the interface of medicine, biology, chemistry, and math. He has coordinated junior faculty mentoring in the Dartmouth Lung Biology COBRE and currently serves in the SYNERGY Office of Research Mentoring.

In 2012, Dean was the recipient of the Faculty Mentor Award.

Selected Publications

Visualizing the Mechanism of Epoxide Hydrolysis by the Bacterial Virulence Enzyme Cif. Bahl CD, Hvorecny KL, Morisseau C, Gerber SA, Madden DR Biochemistry. 2016 Feb 9;55(5):788-97. doi: 10.1021/acs.biochem.5b01229. Epub 2016 Jan 22. PMID: 26752215

Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR. Bahl CD, Hvorecny KL, Bomberger JM, Stanton BA, Hammock BD, Morisseau C, Madden DR Angew Chem Int Ed Engl. 2015 Aug 17;54(34):9881-5. doi: 10.1002/anie.201503983. Epub 2015 Jul 1. PMID: 26136396

A Compact Structure of Cytochrome c Trapped in a Lysine-Ligated State: Loop Refolding and Functional Implications of a Conformational Switch. Amacher JF, Zhong F, Lisi GP, Zhu MQ, Alden SL, Hoke KR, Madden DR, Pletneva EV J Am Chem Soc. 2015 Jul 8;137(26):8435-49. doi: 10.1021/jacs.5b01493. Epub 2015 Jun 24. PMID: 26038984

Intracellular Delivery of Peptidyl Ligands by Reversible Cyclization: Discovery of a PDZ Domain Inhibitor that Rescues CFTR Activity. Qian Z, Xu X, Amacher JF, Madden DR, Cormet-Boyaka E, Pei D Angew Chem Int Ed Engl. 2015 May 11;54(20):5874-8. doi: 10.1002/anie.201411594. Epub 2015 Mar 17. PMID: 25785567

Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain. Amacher JF, Zhao R, Spaller MR, Madden DR PLoS One. 2014;9(8):e103650. doi: 10.1371/journal.pone.0103650. Epub 2014 Aug 19. PMID: 25136860

Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein. Koeppen K, Coutermarsh BA, Madden DR, Stanton BA J Biol Chem. 2014 Jun 13;289(24):17142-50. doi: 10.1074/jbc.M114.555599. Epub 2014 May 8. PMID: 24811177

Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity. Bahl CD, Hvorecny KL, Bridges AA, Ballok AE, Bomberger JM, Cady KC, O'Toole GA, Madden DR J Biol Chem. 2014 Mar 14;289(11):7460-9. doi: 10.1074/jbc.M113.518092. Epub 2014 Jan 28. PMID: 24474692

Stereochemical preferences modulate affinity and selectivity among five PDZ domains that bind CFTR: comparative structural and sequence analyses. Amacher JF, Cushing PR, Brooks L 3rd, Boisguerin P, Madden DR Structure. 2014 Jan 7;22(1):82-93. doi: 10.1016/j.str.2013.09.019. Epub 2013 Nov 7. PMID: 24210758

Reconstitution of homomeric GluA2(flop) receptors in supported lipid membranes: functional and structural properties. Baranovic J, Ramanujan CS, Kasai N, Midgett CR, Madden DR, Torimitsu K, Ryan JF J Biol Chem. 2013 Mar 22;288(12):8647-57. doi: 10.1074/jbc.M112.422105. Epub 2013 Feb 4. PMID: 23382380

Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop. Amacher JF, Cushing PR, Bahl CD, Beck T, Madden DR J Biol Chem. 2013 Feb 15;288(7):5114-26. doi: 10.1074/jbc.M112.401588. Epub 2012 Dec 15. PMID: 23243314