Dr. and Mrs. Tim D. Leon Professor
Ph.D. - Wake Forest University, 1982
Postdoc - Duke University Medical Center
The general subject of research in my laboratory is pancreatic cancer and other diseases of the pancreas, primarily pancreatitis. We have used modern techniques of molecular biology, biochemistry, cell biology, and immunology to develop a comprehensive program of investigation into the biology of normal and diseased pancreatic ductal epithelial cells.
• Several of the main projects in my laboratory center around the study of a complex mucin-like glycoprotein, MUC1, which is believed to play an important role in the normal function of pancreatic ductal epithelia and in the pathogenesis of pancreatic diseases, such as pancreatic adenocarcinoma. We are using the techniques of molecular and cellular biology to examine the regulation of expression and the mechanisms of post-translational processing of MUC1 in tumor cells and other disease conditions as compared to their normal cell counterparts. These studies also provide a paradigm to study basic aspects of the post-translational process (particularly O-glycosylation). We are developing and characterizing new monoclonal antibodies and tumor vaccine reagents for diagnostic and therapeutic uses that target known tumor associated antigens found on mucins. We are also studying the MUC1 promoter.
• I serve as the Principal Investigator of a SPORE in Pancreatic cancer and am the PI on a project in the SPORE program that is directed towards developing and testing vaccines for treating pancreatic cancer. I have previously received funding by the National Cancer Institute (NCI) as PI of a Biomarker Developmental Laboratory (organ focus Pancreas) within the Early Detection Research Network (EDRN). Biomarker Developmental Laboratories have the responsibility for the development and characterization of new biomarkers or the refinement of existing.
Select Funded ProjectsSPORE in Pancreatic Cancer (P50 CA127297)
NCI’s SPOREs (Specialized Programs of Research Excellence) focus on a specific organ site and are designed to enable the rapid and efficient movement of basic scientific findings into clinical settings. The projects in the SPORE focus on translational studies that address basic and clinical issues of importance to improve the outcome of patients with pancreatic cancer, and seek to 1) develop and test novel diagnostic reagents and assays that will improve our ability to detect pancreatic cancer in its early stages; 2) develop and test novel diagnostic strategies including immunotherapy, chemotherapy, and chemoradiation therapy for patients with early and advanced pancreatic cancer, and 3) undertake basic research studies in conjunction with clinical trials that will provide insight at the molecular level into the reasons for success and failure of the different strategies.
All projects in this SPORE use human specimens for translational research directed at reducing the incidence and mortality of pancreatic cancer. In order to provide the necessary specimens, a Pancreas Tumor SPORE Tissue Bank has been developed in cooperation with and under the auspices of the University of Nebraska Medical Center (UNMC) Tissue Procurement Shared Resource.SPORE Supplements:
- Effects of Pancreatic Cancer Microenvironment on Tumor Immune Responses
- Studies will characterize, and quantify the spectrum of cell types and tissue architecture that are present in the tumor microenvironment of patients with pancreatic cancer. We will also prospectively collect data on the functional status of immune cells that are associated with responses to tumors in patients with pancreatic cancer and other neoplasias growing in the pancreas, and perform studies that will provide insight into influence of the pancreatic tumor microenvironment on the systemic immune response (activation, suppression, exhaustion, anergy) by evaluating responses from spleen cells and peripheral blood.
- Collaborative Research Effort to Establish Optimal Methodology Patient Derived Xenograft (PDX) Models from Rapid Autopsy Material
- This proposal will provide a unique resource to the NCI's Patient-Derived Models Repository - matched sets of xenografts from primary tumor and multiple metastatic lesions of individual patients with pancreatic cancer and similar cancers (cholangiocarcinoma, gall bladder tumors).
Pancreatic Cancer Detection Consortium (U01 CA210240)
There are two overall goals of this project. The first is to assemble a unique and robust collection of early lesions and blood samples from patients at risk and those with lesions representing early stages of pancreatic cancer, matched sets of tumors and metastasis and control tissues from the same patients, a tissue resource for use in the discovery and validation of biomarkers for early disease. The second goal is to undertake a series of biomarker discovery and prevalidation projects, proposed within this application and by collaborative studies from other investigators that are part of the Pancreatic Cancer Detection Consortium.