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University of Alabama at Birmingham
The SPORE program in pancreatic cancer at the University of Alabama at Birmingham, led by PI, Dr. Buchsbaum, Director of Radiation Biology with support from Albert LoBuglio, M.D., Cancer Center Director Emeritus, Interim Associate Director of Clinical Research and Distinguished Professor of Medicine, Kirby Bland, M.D., Cancer Center deputy director and chair UAB Department of Surgery and Selwyn Vickers, M.D. (formerly of UAB) chair Department of Surgery University of Minnesota. The projects and supporting infrastructure stem from the cancer center's expertise, including tumor biology, virology/gene therapy, immunobiology and targeted immunotherapy. Specific research projects draw from previously established efforts that have demonstrated the most relevance and promise. The UAB Pancreatic SPORE is composed of two (2) projects. Project 1 is based on a previously characterized novel mechanism for Smad4 protein degradation. Jab1 (Jun activation domain binding protein 1) was identified as a key player in mediating Smad4 protein instability in cells. Further determination of the role of Jab1 in tumor suppressor Smad4 protein degradation should improve our understanding of pancreatic tumorigenesis and may subsequently enable the development of possible therapeutic approaches for pancreatic carcinoma. Project 2 focuses on the hypothesis that a novel group of monoclonal antibodies directed to death receptors 4 and 5 (DR4 and DR5) trigger an apoptotic signal resulting in anti-tumor efficacy which is enhanced by chemotherapy and radiation. This study will evaluate the role of combined modality therapy for the treatment of pancreatic cancer in pre-clinical studies in both in vitro and in vivo animal models to characterize the effects of the antibodies alone and in combinations with chemotherapy and radiation. These studies led by Don Buchsbaum, Ph.D., and Al LoBuglio, M.D., will potentially provide early translational observations and treatment modalities for Phase 1 and Phase 2 studies with death receptor antibodies in combination with chemotherapy and radiation for treatment of pancreatic cancer. The SPORE also funds the following supportive cores: Administrative - Dr. Buchsbaum and Dr. Vickers direct this Core, which will coordinate various components of the grant and facilitate regular meetings with the NCI, other UAB SPOREs and with other institutions. Tissue and Immunopathology Core - William Grizzle, M.D. and Nirag Jhala, M.D. direct this Core, which is the source of banking tissue from specimens of pancreatic cancer and all related cancers. This core provides specimens for each of the projects and is connected to the Clinical Core. Clinical Core - Dr. Wilcox directs this Core, which evaluates all clinical pancreatic cancer patients through the Pancreaticobiliary Center, a designated Center for Excellence. This core facilitates access to clinical trials connected to SPORE research projects. Supporting this endeavor are are Mohamad Eloubeidi, M.D., J. Pablo Arnoletti, M.D., James Posey, M.D., Tina Wood, M.D., John Christein, M.D. and Shyam Varadarajulu, M.D. The Pancreatic SPORE P20 grant also supports the development of conditional knock-out animal models of pancreatic cancer and gene expression profiling of primary pancreatic tumor cells. This effort is led by Dr. Chris Klug and Dr. Martin Johnson. |
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