Dr. Enrique Rozengurt, director of CURE and chief of research for the Vatche and Tamar Manoukian Division of Digestive Diseases, is also director of the Signal Transduction Gastrointestinal Cancer Laboratories. His current focus is on signal transduction pathways leading to proliferation in normal and cancer cells.
The research activities promote the identification of extracellular factors and intracellular signal transduction pathways that stimulate cells to divide. For example, Dr. Rozengurt discovered that neuropeptides (peptides of the bombesin family - found in the central and peripheral nervous system of amphibians) that act as molecular messengers in a rich network of information exchange throughout the organism are potent cellular growth factors for multiple cell types in culture and function as autocrine/paracrine mitogens (chemical cells that induce cell division) for human cancer cells.
He studies the transmission of the neuropeptide signal from surface receptors to the nucleus along a number of transduction pathways, typically protein kinase cascades, that act in a synergistic and combinatorial fashion to promote cell proliferation. His work revealed that regulatory peptides trigger a complex set of molecular responses and specific protein kinase cascades including kinase C and A, mitogen-activated protein kinases (MAPKs) and mTORC1/p70 S6 ribosomal protein kinase.
Recently, he reported on the cloning and expression analysis of a novel protein kinase termed protein kinase D (PKD), the founding member of a novel protein kinase family. PKD is directly activated by phorbol esters (organic tumor promoters) and also is part of a novel phosphorylation cascade downstream of PKC. Research activities in this area include a detailed mutational analysis to define the contribution of different domains of PKD to its regulation and function and to modulate its expression to determine its role in cell regulation.
In addition to serine/threonine protein kinase cascades, Dr. Rozengurt's studies demonstrated that neuropeptides also stimulate a rapid increase in the tyrosine phosphorylation of multiple substrates including focal adhesion kinase (FAK), paxillin, and Crk-associated substrate (CAS). These proteins, which localize at focal adhesion plaques, are implicated in cell migration, proliferation, and transformation.
More recently, Dr. Rozengurt is applying his expertise in signal transduction to the identification of novel crosstalk mechanisms in signaling networks. Positive points of interaction in the network are being identified as novel targets for therapeutic intervention in cancer cells, with a focus on colon and pancreatic epithelial cells.
In conclusion, his work has dissected molecular mechanisms by which growth-promoting factors induce downstream pathways, including protein phosphorylation cascades, and is elucidating the role of these pathways in normal and abnormal cell proliferation.
Enrique Rozengurt, CVM, PhD
Director, Signal Transduction
Gastrointestinal Cancer Laboratories
Director, CURE: Digestive Diseases Research Center