Dr. Enrique Rozengurt is a pioneer in the area of cell growth regulation, from the identification of proteins with novel growth-promoting activity to the elucidation of the intracellular pathways that stimulate cell multiplication. He has published about 400 seminal scientific papers that demonstrate that cultured cells can be stimulated to divide by many molecules in a defined medium. He has subsequently focused on the elucidation of the mechanisms that regulate cell multiplication and motility, a process of importance for the invasiveness of cancer cells.
Rozengurt's work on biologically active peptide-mediated growth is an area of special achievement. He discovered that biologically active peptides are potent cellular growth factors for multiple cell types, including human cancer cells. A typical example is small cell lung cancer (SCLC), which follows a very aggressive clinical course and is characterized by the production of multiple biologically active peptides. He has extended this research to biologically active peptide-sensitive human pancreatic cancer cells and has already demonstrated that they promote growth of pancreatic cancer cells. Following these observations, he reasoned that antagonists capable of blocking the biological effects of multiple biologically active peptides (broad-spectrum peptide antagonists) could be effective for the treatment of SCLC and other peptide-sensitive cancers. Following many experiments in cell lines and in an animal model, one of these antagonists has entered into a Phase I clinical study. It is hoped that this research will lead to new forms of treatment for cancer which will complement current therapies.
Selected Cancer-Related Publications:
Rey O, Chang W, Bikle D, Rozengurt N, Young SH, Rozengurt E. Negative cross-talk between calcium-sensing receptor and Beta-catenin signaling systems in colonic epithelium. J Biol Chem. 2012 Jan 6;287(2):1158-67. Epub 2011 Nov 17
Sinnett-Smith J, Rozengurt N, Kui R, Huang C, Rozengurt E. Protein kinase D1 mediates stimulation of DNA synthesis and proliferation in intestinal epithelial IEC-18 cells and in mouse intestinal crypts. J Biol Chem. 2011 Jan 7;286(1):511-20. Epub 2010 Nov 4
Zhang X, Rozengurt E, Reed EF. HLA class I molecules partner with integrin Beta4 to stimulate endothelial cell proliferation and migration. Sci Signal. 2010 Nov 23;3(149):ra85.
Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res. 2009 Aug 15;69(16):6539-45.
Sinnett-Smith J, Jacamo R, Kui R, Wang YM, Young SH, Rey O, Waldron RT, Rozengurt E. Protein kinase D mediates mitogenic signaling by Gq-coupled receptors through protein kinase C-independent regulation of activation loop Ser744 and Ser748 phosphorylation. J Biol Chem. 2009 May 15;284(20):13434-45. Epub 2009 Mar 16