While TGF-β functions as a tumor suppressor in the premalignant stages of tumorigenesis, paradoxically, it also appears to act as a tumor promoter in advanced cancer. As a first step towards resolving the TGF-β paradox quantitatively, we have developed a dynamic model of the canonical TGF-β/Smad signaling pathway and a macroscopic control systems model of TGF-β regulation of prostate cell population. Our models suggest that the observed elevated level of TGF-β is a consequence of acquired TGF-β resistance exhibited by the cancer cell, not the cause, because a putative TGF-&nbeta; control system must secrete more TGF-β in a futile attempt to achieve the level of tumor suppression attainable with normal, responsive cells. If this hypothesis is validated, its most significant implication will be that the current approach of targeting TGF-β ligand therapeutically may have to be abandoned in favor of re-sensitizing the cells to the tumor suppressive effect of the TGF-β.
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Babatunde A. ("Tunde") Ogunnaike received the B.Sc. degree (with First Class Honors) in Chemical Engineering from the University of Lagos, Nigeria, in 1976; the M.S. degree, in Statistics from the University of Wisconsin-Madison in 1981; and the Ph.D. degree in Chemical Engineering also from the University of Wisconsin-Madison in 1981. From 1981 to 1982, he was a Research Engineer with the Process Control group of the Shell Development Corporation in Houston, Texas; and from 1982 to 1988, he was a professor at the University of Lagos with joint appointments in the Chemical Engineering and the Statistics Departments. He joined the Advanced Control and Optimization group of DuPont Central Science and Engineering in 1989, and was, from 1995 until September 2002, a Research Fellow in DuPont Chemical Sciences and Engineering. An adjunct professor in the Chemical Engineering Department of the University of Delaware since 1989, he joined the faculty as a full professor in September 2002 and currently occupies the William L. Friend Chair of Chemical Engineering. He is the author or co-author of three books including a widely used textbook, Process Dynamics, Modeling and Control, published in 1994 by Oxford University Press; he is also an Associate Editor of the journal Industrial and Engineering Chemistry Research. Dr. Ogunnaike's research interests include modeling and control of industrial processes (polymer reactors, extruders, distillation columns); the application of process analytical technology for control of pharmaceutical processes; identification and control of nonlinear systems; the interaction of process design and process operability; applied statistics; biological control systems; and systems biology with application to neuronal responses and cancer. He is the recipient of the American Institute of Chemical Engineers 1998 CAST Computing Practice Award, the 2004 University of Delaware's College of Engineering Excellence in Teaching award, the 2007 ISA Eckman Award, and the 2008 AACC Control Engineering Practice award.
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