Ilan Spector, Ph.D.

E-mail: ispector@epo.som.sunysb.edu

Our research program has two complimentary goals. The first is the discovery of new pharmacological agents derived from marine organisms. The second is centered on the functions, dynamics, and organization of the actin cytoskeleton, which is emerging as a prominent point of action of marine natural products. We have discovered several new classes of marine natural products that target the actin cytoskeleton with different actin-binding properties. These agents are invaluable as tools for investigating the actin cytoskeleton, which participates in many aspects of cell behavior and plays an important role in cancer and other human diseases. Latrunculin A and B are unusual 16- and 14-membered marine macrolides that sequester monomeric actin and mimics G-actin sequestering proteins. Swinholide A and misakinolide are structurally similar unusual dimeric macrolides that bind to two actin monomers, but swinholide A severs actin filaments while misakinolide caps the barbed end of filaments. These agents disrupt actin organization in a distinctive manner. We are continuously testing new marine compounds for actin inhibition and recently we have identified a number of new and powerful sponge-derived marine macrolides that inducs different patterns of actin organization, and have different actin binding properties.

In addition to actin as a molecular target for marine natural products, we have identified a group of aromatic alkaloids containing a fused tetracyclic pyrido[2,3,4-kl]acridine ring system that exert remarkable effects on cell shape and adhesion and are potent regulators of growth and differentiation of transformed cells.

Collaborations:

Fig 1

• Spector I., N.R.Shochet, Y. Kashman and D. Blasberger (1986): Structure-Activity Study of Latrunculin Effects on Microfilament Organization. J. Cell Biol. 103, 393a
• Spector I., N.R. Shochet, and D. Blasberger, Y. Kashman, (1989): Latrunculins: Novel Marine Toxins that Disrupt Microfilament Organization and Affect Cell Growth: I. Comparison with cytochalasin D. Cell Motility & The Cytoskeleton. 13, 127-144
• Blasberger D., S. Carmely, M. Cojocaru, I. Spector, N.R. Shochet, and Y. Kashman. (1989): On the Chemistry of Latruncluins A and B. Liebigs Ann. Chem. 1171-1188.
• Kaufman A., Yagel, R., Bakalash, R. & Spector, I. (1990) Volume Visualization in Cell Biology. Proceedings of Visualization 90. San Francisco. IEEE Comp. Soc. Press. 160167.
• Bolsover, S., Gilbert, S. & Spector, I. (1990) Intracellular cyclic AMP produces effects opposite to those of cyclic GMP and calcium on shape and motility of neuroblastoma cells. J. Neurosci.
• Shochet N.R., A. Rudi, Y. Kashman, Y. Hod, R. El-Maghrabi and I. Spector (1993): Novel Marine Alkaloids From the Tunicate Eudistoma sp. are Potent Regulators of Cellular Growth and Differentiation and Affect cAMP-Mediated Processes. J. Cell. Physiol. 157: 481-492.
• Shochet N.R., D. Olchovsky, and I Spector (1994): Novel marine alkaloids that regulate cell growth and differentiation. In Vitro 20A: 30-31.
• Bershadsky, A.D., U. Gluck, O.N. Denisenko, T.V. Sklyarova, I. Spector, and A. Ben-Ze'ev (1995) The actin assembly status regulates actin and vinculin expression by a feedback loop. J. Cell Sci. 108:1183-1193
• Shochet N.R. and Spector I. (1995) Marine natural Products that Target the Actin cytoskeleton - Biological and Medical Aspects. 8th International Symposium on Marine Natural Products, Tenerife, Spain. Abst. P. 71
• Bubb, M.R., I. Spector, A.D. Bershadsky, and E.D. Korn (1995), Swinholide A is a cytoskeletal disrupting agent that severs F-actin and forms actin dimers. J. Biol. Chem. 270:3463-3466.
• Terry, D. R., I. Spector, T. Higa, and Bubb, M. R. (1997): Misakinolide A Is A Marine Macrolide That Caps But Does Not Sever Filamentous Actin. J. Biol. Chem. 272:7841-7845.