Luke H. Chao

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

Organelle structure-function: We investigate how proteins self-organize in the birth, life and death of cellular compartments. Our goal is to understand how coupled, coordinated Ångstrom-scale motions propagate into micron-scale cellular rearrangements.

The current focus in our group is the mitochondrial membrane, where morphology is tightly coupled to metabolic function. We are investigating this relationship by asking:

How is organelle shape specialized for a particular function?
How are signals transduced and propagated between membranes?
What is the role of allosteric control in membrane-protein assemblies?
How have organelles evolved to define tissue-specific metabolic niches?

Our approach draws from structural, biophysical, chemical and cellular methods to understand macromolecular assemblies in action, in situ. We enjoy reconstituting protein assembly activity to dissect molecular mechanisms. We use a variety of structural approaches, including electron cryo-microscopy (Cryo-EM), to visualize key conformational states, with an eye to developing new tools to manipulate protein conformational change.

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.