Leonard R. Forte, Ph.D.

Professor ForteL@missouri.edu

Research Interests

Research in my laboratory concentrates on the basic biology of uroguanylin and guanylin, which are newly discovered peptide hormones that regulate cellular functions through stimulation of receptors that produce the intracellular second messenger molecule, cyclic GMP. Uroguanylin was isolated in my laboratory in 1992 by a graduate student in the Pharmacology Ph.D. program at this University named Kent Hamra, who is now an Assistant Professor of Pharmacology at Southwestern Medical School in Dallas. Contemporary approaches using cell and molecular biology techniques have been applied to investigations of fundamental mechanisms of action as well as the physiological roles of uroguanylin in the body. This research has led to new concepts of how uroguanylin participates in the physiological control of body sodium balance and blood pressure through regulatory actions on the kidney as well as to novel pharmacological applications of uroguanylin for both the diagnosis and treatment of colon cancer. Our studies involving the development of peptide analogues that are structurally related to uroguanylin are carried out in my laboratories and those of my collaborators within the Radiopharmaceutical Sciences Institute and the Biomolecular Imaging Center located in the Harry S Truman Memorial Veteran’s Hospital. These experimental drugs are synthesized using solid-state peptide synthesis methods and the peptide molecules are then labeled with different radioisotopes for either the detection of colon cancers that have spread to other organs of the body or for application in the therapy of colon tumors. Mouse models bearing human colon cancers are used for the experimental diagnostic research and transgenic mice that spontaneously form intestinal tumors are used for testing the anti-cancer effectiveness of novel therapeutic agents in this class of uroguanylin-related peptides. Uroguanylin analogues labeled with the radionuclide, 111Indium, are used to localize metastatic forms of colon cancers using SPECT (single photon-emitting computed tomography) imaging with an instrument designed for preclinical studies in mice that is part of the VA Biomolecular Imaging Center’s new imaging equipment. These peptides can also be labeled with another radionuclide, 64Copper, which can be detected through the use of PET (positron emission tomography) using an imaging instrument in this center that is designed for experiments with mice. For therapeutic approaches using uroguanylin-like drugs, a transgenic mouse model for human tumorigenesis, the multiple intestinal neoplasia (Min) mouse, is treated orally with uroguanylin or its structural analogues to assess the in vivo potency and effectiveness of these experimental agents. In summary, my research interests focus on both the basic biology of uroguanylin and the application of novel approaches to develop drugs based on this family of cyclic GMP-regulating peptide hormones.

Professional Information

• B.S. in Biology and Chemistry from Austin Peay State College.
• Ph.D. in Pharmacology from Vanderbilt University.
• Joined faculty of the MU Department of Pharmacology in June, 1969.
• Joined the Truman VA Research Service in 1974.
• Research Career Development Award from the NIH 1974-1979.
• Acting Associate Chief of Staff-R&D for Truman VA Research 1979-81.
• Professor of Pharmacology 1981-present.
• Interim Chair of Pharmacology 1981-83
• VA Research Career Scientist 1988-98.
• Gold Chalk Teaching Award, 1995, MU Graduate and Professional Council.
• Visiting Professor, Melbourne Univ., Parkville, Victoria, Australia 1989-90.
• Senior VA Research Career Scientist 1998-present.
• Professor, MU Radiopharmaceutical Sciences Institute, 1999-present.
• Investigator, Mount Desert Island Biological Laboratory, 2000-present.
• Doutor Honoris Causa, Universidade Estadual do Ceara, Fortaleza, Brazil, Honorary doctorate degree for the discovery of uroguanylin and its physiological contributions to sodium balance, 2000.
• Professor, MU Nuclear Science and Engineering Institute, 2002-present.
• Professor, MU Dept. Medical Pharmacology and Physiology, 2002-present.

Methodology/Techniques

The fundamental methods of cell and molecular biology are used for a substantial part of our investigations in this laboratory. A human T84 colon cancer cell line is the main cell model for our work in colon cancer that involves basic studies of the uroguanylin receptor-cyclic GMP signaling pathway. A proximal tubular-like cell line derived from opossum kidney (OK) serves as a cell model for uroguanylin target cells in renal tubules of the kidney. Some animal experimentation is done in the projects focused on the development of new drugs for the diagnosis and therapy of colon cancer. We use the SCID mouse that has been implanted with human colon cancer cells to test the diagnostic and therapeutic agents that are under development in this laboratory. Dr. Forte’s laboratories are located in the Medical Research Service of the Harry S Truman Memorial Veterans’ Hospital where the laboratories of faculty members in the Radiopharmaceutical Sciences Institute of the University of Missouri School of Medicine are also located.