Joshua Chappie
Assistant Professor
Nancy and Peter Meinig Family Investigator in the Life Sciences

Joshua Chappie

Phone

(607) 253-3654

Address

Department of Molecular Medicine
C3-165 Vet Medical Center
Cornell University
Ithaca, NY  14853


Email

Web Sites

Department Profile
Background

Joshua Chappie is an Assistant Professor in the Department of Molecular Medicine.  He earned B.S./M.S. degrees in Biochemistry at Brandeis University in 2003 and a Ph.D. degree in Biophysics from the Scripps Research Institute in 2009.  He was a Postdoctoral Fellow in the Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases at NIH from 2009-2013.  In 2013, he joined the Department of Molecular Medicine as an Assistant Professor.

Research Description

The Chappie lab utilizes a combination of structural biology, biochemistry, and cell biology to dissect the mechanisms of complex molecular machines. Research efforts are divided between two major areas: 1) the structure and function of mechanochemical GTPases and 2) investigating the mechanisms of bacterial defense systems, specifically those targeting modified DNA. Together these endeavors have important implications for human diseases such as centronuclear myopathy, Charcot–Marie–Tooth disease, and cholesterol trafficking disorders and also in the development of new therapeutic strategies for treating antibiotic-resistant bacterial infections in humans and animals. They maintain a collaborative, interdisciplinary approach to science and have partnered with investigators at Cornell and NIH to tackle challenging biological problems.

Selected
Publications

Chappie JS, Dyda F.  Building a fission machine--structural insights into dynamin assembly and activation.  J Cell Sci. 2013 Jul 1;126(Pt 13):2773-84. doi: 10.1242/jcs.108845. Epub 2013 Jun 18. Review.  PMID: 23781021

Maggin JE, James JA, Chappie JS, Dyda F, Hickman AB.  The amino acid linker between the endonuclease and helicase domains of adeno-associated virus type 5 Rep plays a critical role in DNA-dependent oligomerization.  J Virol. 2012 Mar;86(6):3337-46. doi: 10.1128/JVI.06775-11. Epub 2011 Dec 28.  PMID: 22205752

Chappie JS, Mears JA, Fang S, Leonard M, Schmid SL, Milligan RA, Hinshaw JE, Dyda F.  A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke.  Cell. 2011 Sep 30;147(1):209-22. doi: 10.1016/j.cell.2011.09.003. PMID:  21962517

Wilson-Kubalek EM, Chappie JS, Arthur CP.  Helical crystallization of soluble and membrane binding proteins.  Methods Enzymol. 2010;481:45-62. doi: 10.1016/S0076-6879(10)81002-X.  PMID:  20887852

Chappie JS, Acharya S, Leonard M, Schmid SL, Dyda F.  G domain dimerization controls dynamin's assembly-stimulated GTPase activity.  Nature. 2010 May 27;465(7297):435-40. doi: 10.1038/nature09032. Epub 2010 Apr 28.  PMID: 20428113

Chappie JS, Acharya S, Liu YW, Leonard M, Pucadyil TJ, Schmid SL.  An intramolecular signaling element that modulates dynamin function in vitro and in vivo.  Mol Biol Cell. 2009 Aug;20(15):3561-71. doi: 10.1091/mbc.E09-04-0318. Epub 2009 Jun 10.  PMID: 19515832

Littlefield KP, Ward AB, Chappie JS, Reedy MK, Bernstein SI, Milligan RA, Reedy MC.  Similarities and differences between frozen-hydrated, rigor acto-S1 complexes of insect flight and chicken skeletal muscles.  J Mol Biol. 2008 Sep 5;381(3):519-28. doi: 10.1016/j.jmb.2008.06.029. Epub 2008 Jun 17.  PMID: 18588896

Ramachandran R, Surka M, Chappie JS, Fowler DM, Foss TR, Song BD, Schmid SL.  The dynamin middle domain is critical for tetramerization and higher-order self-assembly.  EMBO J. 2007 Jan 24;26(2):559-66. Epub 2006 Dec 14.  PMID: 17170701

Cheeseman IM, Chappie JS, Wilson-Kubalek EM, Desai A.  The conserved KMN network constitutes the core microtubule-binding site of the kinetochore.  Cell. 2006 Dec 1;127(5):983-97.  PMID: 17129783

Chappie JS, Cànaves JM, Han GW, Rife CL, Xu Q, Stevens RC.  The structure of a eukaryotic nicotinic acid phosphoribosyltransferase reveals structural heterogeneity among type II PRTases.  Structure. 2005 Sep;13(9):1385-96.  PMID: 16154095

Nimigean CM, Chappie JS, Miller C.  Electrostatic tuning of ion conductance in potassium channels.  Biochemistry. 2003 Aug 12;42(31):9263-8.  PMID: 12899612