Research interests

While most extracellular proteins has in their structure a special signal peptide, required for their export through endoplasmic reticulum and Golgi, a large group of secreted proteins are devoid of signal peptides, and they are exported through insufficiently studied nonclassical mechanisms.

Our laboratory studies the stress-induced nonclassical export, of FGF1 and IL1alpha, two ubiquitous pro-inflammatory and pro-angiogenic molecules. The goals of this project is to understand how multiprotein release complexes are formed, how the released proteins are transported to the cell membrane and how they exit to the extracellular compartment without using the classical mechanism of exocytosis. The understanding of these processes will facilitate the development of new clinical approaches to the regulation of angiogenesis, inflammation and tumor growth.

Additionally, our laboratory studies the interaction between FGF/FGFR, Jagged(Delta)/Notch and thrombin/PAR1 signaling, three major regulatory systems involved in practically all of the aspects of organism development and organ formation. In particular, thrombin stimulation and downregulation of Notch signaling induce FGF1 expression and release and the acquisition of the angiogenic phenotype by the cells. The aim is to understand molecular mechanisms underlying the cross-talk between FGF, Notch and thrombin signaling and to use this knowledge for the treatment of cardiovascular and oncological disorders.

Publications

• Prudovsky, I., Tarantini, F., Landriscina, M., Neivandt, D., Soldi, R., Kirov, A., Small, D., Kathir, KM, Rajalingam D., Kumar, TKS. Secretion Without Golgi. J Cell. Biochem., 2008; 3: 1327-1343.
• Lee, CW, Raskett, CM, Prudovsky, I, Altieri, DC. Molecular Dependence of Estrogen Receptor-Negative Breast Cancer on a Notch-Survivin Signaling Axis. Cancer Res., 2008, 68: 5273-81.
• Di Serio, C, Doria, L, Pellerito, S, Prudovsky, I, Micucci, I, Massi , D, Landriscina, M, Marchionni, N, Masotti, G., Tarantini,  F. The Release of Fibroblast Growth Factor-1 from Melanoma Cells Requires Copper Ions and is Mediated by Phosphatidylinositol 3-kinase/Akt Intracellular Signaling Pathway. Cancer Letters, 2008, 267:67-74.
• Leclair, RJ, Wang, Q, Benson, MA, Prudovsky, I, Lindner, V. Intracellular Localization of Cthrc1 Characterizes Differentiated Smooth Muscle Cells". Arterioscler Thromb Vasc Biol., 2008; 28:1332-1338.
• Duarte, M, Kolev, V, Kacer, D, Mouta-Bellum, C, Soldi, R, Graziani, I, Kirov, A, Friesel, R, Liaw, L, Small, D, Verdi, J, Maciag, T, Prudovsky, I. Novel Cross-Talk between Three Cardiovascular Regulators: Thrombin Cleavage Fragment of Jagged 1 Induces FGF1 Expression and Release, 2008, Mol. Biol. Cell. Epub ahead of print.
• Nikopoulos, G., Duarte, M., Kubu, C., Bellum, S., Friesel, R., Maciag, T., Prudovsky, I., Verdi, J., Soluble Jagged1 Attenuates Lateral Inhibition, Allowing for Expansion of Neural Crest Stem Cells. Stem Cells, 2007; 25: 3133-3142.

Grants

• 2001 to 2008 — 1000000.00 — Growth Factor Signaling and Traffick in Angiogenesis from NIH
• 2005 to 2010 — 625000.00 — P20RR15555 Project 4 "Mechanism of Non-classical Release of the Angiogenesis Regulator, Interleukin 1α" from NIH
• 2008 to 2009 — 75000.00 — FGF-Mediated Tumor Growth Induced by Notch Signaling Inhibition from Maine Cancer Foundation