Edwin R. Chapman, Phd
Professor, Neuroscience; Investigator, Howard Hughes Medical Institute
Office: 9557 WIMR 2
Mail: 5505 WIMR 2
1111 Highland Avenue
- Lab Website
- Chapman Lab
Neuronal exocytosis is triggered by Ca2+ and occurs via the abrupt opening of a pre-assembled fusion pore. Subsequent dilation of the pore results in the complete fusion of the vesicle membrane with the plasma membrane. We are currently identifying and reconstituting the sequential protein-protein and protein-lipid interactions that underlie excitation secretion coupling. To delineate this pathway, we have primarily focused on the Ca2+-binding synaptic-vesicle protein, synaptotagmin, which appears to function as the Ca2+-sensor that regulates release.
Our work is also focused on components of the “SNARE-complex”, which is thought to form the core of the fusion apparatus. The rapid kinetics of exocytosis (<1 ms) indicate that only a handful of molecular rearrangements occur to couple Ca2+-synaptotagmin to the opening of the fusion pore. We are using a combination of biochemical, biophysical, imaging, spectroscopic and genetic approaches to delineate the interactions/conformational changes that occur during this window of time.
Current experiments include the reconstitution of Ca2+-triggered membrane fusion in vitro, visualization of protein rearrangements and vesicle dynamics inside living cells, genetic manipulations to modulate the efficiency and kinetics of synaptic transmission, and time resolved optical and electrophysiological studies to dissect individual steps in the release pathway and to manipulate the properties of the exocytotic fusion pore.
More recently, we have expanded our efforts to study how changes in membrane trafficking underlie synaptic plasticity and to elucidate the molecular basis for asynchronous synaptic transmission.
Finally, we study the actions of the clostridial neurotoxins, which cause botulism and tetanus poisoning, with emphasis on identifying the pathways of entry, the receptors that mediate entry, and the translocation of the toxins across membranes.
Honors & Awards
- 2017 Member of the NIH study section SYN
- 2015 Editorial Board, JGP
- 2012 Kellett Mid-Career Award
- Rose Awards (to J.B. 2003, M.D. 2004, M.C. 2008, E.H. 2009, S.E.K. 2012, H.B. 2015, C.S.E. 2016); for outstanding thesis in the neurosciences
- 2005 HHMI Investigator
- 2004 Romnes Award
- 1999 Pew Scholars Award
- 1998 Shaw Scientist Award
- Ewa Bomba-Warczak, Joel M. Brittain, Jason D. Vevea, Annette Figueroa-Bernier, William H. Tepp, Eric A. Johnson, Felix L. Yeh and Edwin R. Chapman. (2016). Interneuronal transfer and action of tetanus toxin and botulinum neurotoxins A and D. Cell Reports 16(7):1974-87. PMCID: PMC4988880. Note: this paper is featured in Time Magazine (cover article) and on the NPR show ‘On Point with Tom Ashbrook’
- Bao, H., Goldschen-Ohm, M.O., Jeggle, P., Chanda, B., Edwardson, J.M. & Chapman, E.R.. (2016). Exocytotic fusion pores are composed of both lipids and proteins. Nature Struct. Mol. Biol. 23(1): 67-73. PMCID: PMC4756907. Note: this was a cover/featured article.
- *Bai, H., *Xue, R., Zhang, L., Yethiraj, A., Cui, Q. and Chapman, E.R. (2016). Different states of synaptotagmin control evoked versus spontaneous synaptic vesicle exocytosis. Nature Comm. 7: 10971. PMCID: PMC4804166. *equal contribution
- Yao, J, Gaffaney, J.D., Kwon, S.E. and Chapman, E.R. (2011). Doc2 is a Ca2+-sensor required for asynchronous neurotransmitter release.Cell 147(3):666-77. PMCID:PMC3220409
- Hui, E., Johnson, C., Yao, J., Dunning, M. and Chapman, E.R.(2009).Synaptotagmin-mediated bending of the target membrane is a critical step in Ca2+-regulated fusion.Cell 138: 709-721.PMCID: PMC2758036
- *Chai, Q., *Arndt, J.W., *Dong, M., Tepp, W.H., Johnson, E.A., #Chapman, E.R.and #Stevens, R.C.. (2006). Structural basis of receptor recognition by botulinum neurotoxin B.Nature 444: 1096-1100.
*equal contribution #corresponding authors
- Dong, M., Yeh, Y., Tepp, W.H., Dean, C., Johnson, E.A., Janz, R. andChapman, E.R.. (2006).SV2 is the protein receptor for botulinum neurotoxin A.Science312:592-596.
- Tucker, W.T., Weber, T. and Chapman, E.R.. (2004) Reconstitution of Ca2+-triggered membrane fusion by synaptotagmin and SNAREs.Science 304: 435-438.