Luke H. Chao

Assistant Professor
Department of Molecular Biology, Massachusetts General Hospital
Department of Genetics, Harvard Medical School

Our group is interested in understanding the structural and biophysical determinants of membrane morphology. Active areas of interest include: mitochondrial dynamics (and cristae morphology), bacterial ultrastructure, and plasma membrane projections.

We apply an integrative approach (including cryo-EM, cryo-ET and in vitro reconstitution) to capture protein/membrane assemblies in action.

We're fascinated by the dialogue between macromolecular machines and their environment. Proteins shape membranes by converting energy into motion. In turn, proteins respond to signals from their local membrane environment.

Questions that excite us include:
How membrane lipid composition and distribution influences protein conformational change and subcellular dynamics?
How physical forces influence structural change across multiple membranes?
How evolution shapes the regulation of membrane assemblies?
Cellular environments are an exciting frontier to understand molecular and cellular shape change. We are interested in understanding these relationships under different physiological states, in specific tissue environments, and in disease.

Selected Publications:

Y. Chou, C. Cuevas, M. Carocci, S. Stubbs, M. Ma, D. Cureton, L.H. Chao, F. Evesson, K. He, P. Yang, S. Whelan, S. Ross, T. Kirchhausen, and R. Gaudin. Identification and characterization of a novel broad-spectrum virus entry inhibitor. J. Virology 2016; 90(9):4494-510.

L.H. Chao, D.E. Klein, A.G. Schmidt, J.M. Peña, S.C. Harrison. Sequential conformational rearrangements in flavivirus membrane fusion. eLife 2014; 3:e04389. PMID: 25479384

M.M. Stratton, I-H. Lee, M. Bhattacharyya, S.M. Christensen, L.H. Chao, H. Schulman, J.T. Groves, J. Kuriyan. Activation-triggered subunit exchange between CaMKII holoenzymes facilitates the spread of kinase activity. eLife 2014;3:e01610 arXiv:1312.5376.

M.M. Stratton, L.H. Chao, H. Schulman, J. Kuriyan. Structural studies on the regulation of Ca2+/calmodulin dependent protein kinase II. Current Opinion in Structural Biology, 2013 Apr 23(2): 292-301.

L.H. Chao, M.M. Stratton, I-H. Lee, O.S. Rosenberg, J. Levitz, D.J. Mandell, T. Kortemme, J.T. Groves, H. Schulman, J. Kuriyan. A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin-dependent kinase II holoenzyme. Cell, 2011 Sep 146(5): 732-45. PMC3184253.

L.H. Chao*, P. Pellicena*, S. Deindl, L.A. Barclay, H. Schulman, J. Kuriyan. Inter-subunit capture of regulatory segments is a component of cooperative CaMKII activation. Nature Structural and Molecular Biology, 2010 Mar 17(3): 264-72. PMC2855215 *denotes equal contribution.