The Twomey Lab opened in January, 2021.
Our lab has three main interests. (1) Time-resolved cryo-electron microscopy. How can we understand how proteins work as a function of time? To do this we are developing new techniques for time-resolved specimen preparation in cryo-electron microscopy and cryo-electron tomography. (2) Ionotropic glutamate receptors regulate the majority of excitatory neurotransmission. How do they function? How do they assemble into functional units? What is the mechanistic basis of their contribution to neurological disease? How can we leverage this information for therapeutic design? (3) The mechanism of tight junction function in blood retinal and blood brain barriers. How do tight junctions form selective barriers to regulate nutrient homeostasis and immune privilege? How can we leverage our understanding of tight junctions to improve treatments of retinopathies and neurodegenerative diseases? Can we use our findings to improve drug delivery to the nervous system?
Twomey, E.C.*, Ji, Z.*, Wales, T.E., Bodnar, N.O., Ficarro, S.B., Marto, J.A., Engen, J.R., Rapoport, T.A. “Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.” Science, Aug 2;365(6452). pii: eaax1033. PMID: 31249135.
Twomey, E.C., Yelshanskaya, M.V., Vassilevski, A.A., Sobolevsky, A.I. “Mechanisms of channel block in calcium-permeable AMPA receptors.” Neuron, 99: 956-968 (2018). PMID: 30122377. Featured as issue cover.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Channel opening and gating mechanism in AMPA-subtype glutamate receptors.” Nature, 549: 60-65 (2017). PMID: 28737760.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes.” Neuron, 94: 569-580 (2017). PMID: 28472657.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.” Science, 353: 83-86 (2016). PMID: 27365450.