Office Phone: 301.405.6925
Office Address: 3283 Bio-Psych
- BSCI 426 Membrane Biophysics
- BIOL 622 Membrane Transport Phenomena
- BSCI 451/BSCI 651 Physical Chemistry for Biologists
- BSCI 327 Physics of Living Systems
Graduate Program Affiliations
- BISI - BISI-Physiological Systems (PSYS)
- BISI - BISI-Molecular & Cellular Biology (MOCB)
- Chemistry and Biochemistry
I have a long-standing research interest in the molecular basis for the function of membrane channels, including voltage gating and selectivity. I also have considerable interest in the cell physiology of membrane channels, especially those located in the mitochondrial outer membrane. Currently the focus is to understand how these channels are involved in mitochondria-mediated apoptosis. I believe they are involved in the decision-making process, the release of proteins from mitochondria that activate the execution phase of apoptosis. These channels are: 1) VDAC, a 30kDa channel that controls the flow of metabolites across the outer membrane; 2) ceramide channels, large, protein permeable, channels formed by the self-assembly of a lipid, ceramide. The research is mechanistic in nature and we use a variety of techniques from electrophysiological recordings to electron microscopy.
The main current research focus is ceramide channels. The ability of lipids normally found in cell membranes to self-assemble into large, stable channels is unprecedented in the literature. Moreover, their regulation by proteins is also totally novel. We believe that the proteins affect the channel in much the same way that an allosteric modifier influences ther structure of a protein. Beyond these biophysical considerations, the role of ceramide channels in a critical, decision-making step in the initiation of apoptosis, has tremendous implications for both basic and applied research.
Tan, W., Lai, J.C., Miller. P., Stein, C.A., and Colombini, M. 2007. Phosphorothioate Oligonucleotides Reduce Mitochondrial Outer Membrane Permeability to ADP. American Journal of Physiology 292: C1388-C1397. Full Text
Tan W., Loke Y.H., Stein C.A., Miller P. and Colombini M. 2007. Phosphorothioate Oligonucleotides Block the VDAC Channel. Biophysical Journal 93: 1184-1191. Full Text
Tan W. and Colombini M. 2007. VDAC closure increases calcium ion flux. Biochimica et Biophysica Acta. 1768: 2510-2515. Full Text
Stiban J., Caputo L. and Colombini M. 2008. Ceramide synthesis in the endoplasmic reticulum can permeabilize mitochondria to pro-apoptotic proteins. Journal of Lipid Research 49: 625-634. Full Text
Siskind L.J., Feinstein, L., Yu, T., Davis, J.S., Jones, D., Choi, J., Zuckerman, J.E., Tan, W., Hill, R.B., Hardwick, J.M. and Colombini, M. 2008. Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels. Journal of Biological Chemistry 283: 6622-6630. Full Text
Hiller, S., Garces, R.G., Malia, T.J. Orekhov, V.Y., Colombini, M. and Wagner, G. 2008. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 321: 1206-1210. Full Text.
Stein, C.A. and Colombini, M. 2008. Specific VDAC inhibitors: phosphorothioate oligonucleotides. Journal of Bioenergetics and Biomembranes 40: 157-162. Full Text
Colombini, M. 2009. The Published 3-D structure of the VDAC channel: native or not? Trends in Biochemical Sciences 34: 382-389. Full Text
Ganesan, V., Perera, M.N., Colombini, D., Datskovskiy, D., Chadha, K., and Colombini, M. 2010. Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane. Apoptosis 15: 553-562 Full Text
Colombini, M. 2010. Ceramide channels and their role in mitochondria-mediated apoptosis. Biochimica et Biophysica Acta (Bioenergetics) 1797: 1239-1244. Full Text
Ganesan, V. and Colombini, M. 2010. Regulation of Ceramide Channels by Bcl-2 Family Proteins. FEBS Letters 584: 2128-2134. Full Text
Samanta, S., Stiban, J., Maugel, T.K. and Colombini, M. 2011. Visualization of Ceramide Channels by Transmission Electron Microscopy Biochimica et Biophysica Acta 1808(4): 1196-1201. Full Text
Shao, C., Bing, S., Colombini, M. and DeVoe, D. 2011. Rapid microfluidic perfusion enabling kinetic studies of lipid ion channels in a bilayer lipid membrane chip. Annals of Biomedical Engineering 39: 2242-2251. Full Text
Lin, S.H., Perera, M.N., Nguyen, T., Datskovskiy, D., Miles, M., Colombini, M. 2011. Bax forms two types of channels, one is voltage-gated. Biophysical Journal 101: 2163-2169. Full Text
Colombini, M. 2012. VDAC structure, selectivity, and dynamics. Biochimica et Biophysica Acta 1818:1457-1465 Full Text
Colombini, M. and Mannella, C.M. 2012. VDAC, the early days. Biochimica et Biophysica Acta 1818:1438-1453 Full Text
Perera, M.N., Ganesan, V., Siskind, L.J., Szulc, Z.M., Bielawski, J., Bielawska, A., Bittman, R., and Colombini, M. 2012. Ceramide channels: influence of molecular structure on channel formation in membranes. Biochimica et Biophysica Acta 1818: 1291-1301. Full Text
Perera, M.N., Lin, S.H., Peterson, Y.K., Bielawska, A., Szulc, Z.M., Bittman, R., and Colombini, M. 2012. BAX, Bcl-xL exert their regulation on different sites of the ceramide channel. Biochemical Journal 445: 81-91. Full Text
Shao, C., Sun, B., Colombini, M. and DeVoe, D. 2012. Dynamics of ceramide channels detected using a microfluidic system. PLoS One 7(9):e43513. Full Text
Ganesan, V. Walsh, T., Chang, K-T, and Colombini, M. 2012. The dynamics of Bax channel formation: Influence of ionic strength. Biophysical Journal 103: 483-491. Full Text
Colombini, M. 2012. Mitochondrial outer membrane channels. Chemical Reviews 112 (12),pp 6373–6387
Colombini, M. 2013. Membrane channels formed by ceramide. Handbook of Experimental Pharmacology 215: 109-126.
Colombini, M. 2013. Mitochondrial Outer Membrane and the VDAC Channel. In: Lennarz, W.J. and Lane, M.D. (eds.) The Encyclopedia of Biological Chemistry, Vol. 3, pp. 159-161. Waltham, MA: Academic Press.
Lin, S.H., Cherian, N., Wu, B., Phee, H., Cho, C. and Colombini M. 2014. Bax Channel Triplet: Cooperativity and Voltage Gating. Biochemical Journal 459: 397-404. Full text
Chang, K-T., Anishkin, A. Patwardhan, G.A., Beverly, L.J., Siskind, L.J. and Colombini, M. (2015) Ceramide Channels: destabilization by Bcl-xL and role in apoptosis. Biochimica et Biophysica Acta 1848: 2374-2384. Full text
Perera, M.N., Ganesan, V., Siskind, L.J., Szulc, Z.M., Bielawska, A., Bittman, R. and Colombini, M. (2015) Ceramide channel: structural basis for selective membrane targeting. Chemistry and Physics of Lipids (in press) Full text
Head, S., Shi, W., Zhao, L. , Gorshkov, K., Pasunooti, K. , Chen, Y. , Deng, Z., Li, R-J., Shim, J.S., Tan, W., Hartung, T., Zhang, J., Zhao, Y., Colombini, M., Liu, J.O. (2015) The antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells. Proc. Natl. Acad. Sci. U.S.A. (in press) Full text
Colombini, M. (2015) Ceramide Channels In: Delcour, A. (ed.) Electrophysiology of Unconventional Channels and Pores, Springer, (in press).
The Meller Basic Medical Research Award, 1976
College of Chemical and Life Sciences Faculty Award for Excellence in Research, 1995
Chair of the Bioenergetics Subgroup of the Biophysical Society 2004-07
On the Council of the Biophysical Society 2008-12
Fellow of the AAAS 2013
H index is 57
- McGill University, B.Sc., 1970 Honors in Chemistry and Biochemistry
- McGill University, Ph.D., 1974 Structure and mode of action of membrane transport systems; molecular basis for voltage control of channel-forming proteins.