Marco Colombini

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.

Siskind, L. J., Fluss, S., Bui, M., and Colombini, M. 2005. Sphingosine forms channels in membranes that differ greatly from those formed by ceramide. Journal of Bioenergetics and Biomembranes. 37: 227-236. Full Text

Rostovtseva, T.K., Tan, W., and Colombini, M. 2005. On the role of VDAC in apoptosis: fact and fiction. Journal of Bioenergetics and Biomembranes. 37: 129-142.

Siskind, Leah J. 2005. Mitochondrial Ceramide and the Induction of Apoptosis. Journal of Bioenergetics and Biomembranes. 37: 143-153. Full Text

Stiban, J., Fistere Jr., D., and Colombini, M. 2006. Dihydroceramide hinders ceramide channel formation: implications on apoptosis. Apoptosis 11:773-80. Full Text

Elrick, M.J., Fluss, S., and Colombini, M. 2006. Sphingosine, a product of ceramide hydrolysis by ceramidase, influences the formation of ceramide channels. Biophys. J. 91: 1749-1756. Full Text

Siskind, L. J., Kolesnick, R.N. and Colombini, M. 2006. Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion 6:118-25. Full Text

Lai, J.C., Tan, W., Benimetskaya, L., Miller, P., Colombini, M., and Stein, C.A. 2006. A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC. Proceedings of the National Academy of Sciences U.S.A., 103:7494-7499. Full Text

Anishkin, A., Sukharev, S., and Colombini, M. 2006. Searching for the molecular arrangement of transmembrane ceramide channels. Biophysical Journal, 90:2414-2426. Full Text

Lai, J.C., Brown, B.D., Voskresenskiy, A.M., Vonhoff, S., Klussman, S., Tan, W., Colombini, M., Weeratna, R., Miller, P., Benimetskaya, L., and Stein, C.A. 2007. Comparison of D-G3139 and Its Enantiomer L-G3139 in Melanoma Cells Demonstrates Minimal In Vitro but Dramatic In Vivo Chiral Dependency. Molecular Therapy, 15: 270-280.

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

H index: 39

The Meller Basic Medical Research Award, 1976

College of Chemical and Life Sciences Faculty Award for Excellence in Research, 1995