Newswise — Researchers at North Dakota State University, Fargo, (NDSU) have received a $10.5 million, five-year research grant from the National Institutes of Health (NIH) for new strategies for targeting protease (pro' tee aze) in disease. The research team is led by Mukund Sibi, who is a James A. Meier Professor of Chemistry and Molecular Biology at NDSU.
The funding continues a nationally competitive biomedical research center at NDSU, focused on the study of proteases in disease. The research has a strong biology component with cancer and asthma as the primary disease targets. "A major scientific goal of this research includes understanding the biological role played by matrix metalloproteinases (MMPs) and histone deacetylases (HDAC) in cancer and other diseases such as asthma," said Sibi. NDSU investigators participating in the research include: Greg Cook, Glenn Dorsam and Sheri Dorsam of the Department of Chemistry and Molecular Biology; Bin Guo, Department of Pharmaceutical Sciences, and Jane Schuh, Department of Veterinary and Microbiological Sciences.
NDSU researchers will investigate how proteases, a key biological player in several diseases, impact cancer. According to Dr. Sibi, the studies have the potential to provide novel therapeutics in cancer treatment. Major scientific focus will be the development of a program focused on diseases that are impacted by proteases. "Understanding the biological role played by proteases, such as matrix metalloproteinases (MMP) and histone deacetylases (HDAC) in cancer and other diseases such as asthma and lupus will be a major scientific goal. It represents an exciting and emerging target for cancer chemotherapy and treatment of autoimmune diseases such as lupus," said Sibi.
The MMPs belong to a class of enzymes called proteases that degrade proteins by cutting them into small pieces. Too much or too little MMP activities can contribute to diseases such as arthritis, cancer, and diabetes. Controlling enzyme activity by using pharmaceuticals is seen as a potential strategy for treating the diseases.
In 2001, NDSU was awarded a five-year, $8.25 million research grant from the National Institutes of Health (NIH) " National Center for Research Resources (NCRR) to establish a Center for Biomedical Research Excellence. At the time, it was the single largest research grant ever to be awarded to NDSU faculty and led to the creation of the
NDSU Center for Protease ResearchThe focus of the first five years of research was chemically-oriented biomedical research aimed at designing, generating, evaluating and delivering potent inhibitors against MMP and HDAC enzymes implicated in numerous health-related disorders. Activity will continue in this area.
With the recently awarded $10.5 million from the NIH, the NDSU biomedical research initiative shifts toward increasing the understanding of the biological role of proteases and other hydrolytic enzymes in disease. "The research focuses on the role enzymes play in how tumors are established, progress and spread. We will investigate highly relevant causative mechanisms for malignant transformation and metastasis with special emphasis on prostate cancer and T cell leukemia and lymphomas," said Sibi.
The NDSU Center for Protease Research is a multidisciplinary research center whose aim is to help combat diseases including arthritis, diabetes and cancer. The Center combines expertise from various NDSU departments in multi-disciplinary basic research that could help combat diseases. The Center for Protease Research has initiated several programs to increase biomedical research activities in North Dakota including seed grants for NDSU faculty, graduate and postdoctoral fellowships and summer research fellowships for faculty and undergraduates from regional four-year colleges. This has provided for integration of research and graduate education in chemistry, cell biology, and pharmacy at NDSU to a previously unseen extent. http://www.ndsu.nodak.edu/cobre/
About the NDSU Research TeamDr. Mukund P. Sibi, professor of chemistry and molecular biology, has a wide range of synthetic expertise. His group has developed novel methods for the preparation of succinates, a common structural motif found in known MMP inhibitors. He also has made extensive contributions to the field of amino acid chemistry, radical chemistry and Chiral Lewis acid-mediated reactions. Dr. Sibi is currently the director for the Center for Protease Research at NDSU. He received his B.S. and M.S. degrees from Bangalore University, India, and his Ph.D. from City University of New York.
Dr. Greg Cook, associate professor of chemistry and molecular biology, received his undergraduate degree at Olivet College, Olivet, Michigan, and completed M.S. and Ph.D. work at Michigan State University. Dr. Cook spent two years as a NIH Postdoctoral Fellow in the laboratories of Prof. Barry M. Trost in Stanford. Dr. Cook's research interests are in the area of synthetic organic chemistry, developing new synthetic methodology utilizing allyl organometallics.
Dr. Glenn Dorsam, assistant professor of chemistry and molecular biology, received his bachelor's degree from Michigan State University and his Ph.D. from Virginia Commonwealth University. He was a postdoctoral fellow at the University of California, San Francisco. Dr. Dorsam has established a research program based on the epigenetic transcriptional regulation controlling how cells proliferate and differentiate. He is specifically interested in the molecular mechanisms governing Ikaros-mediated transcriptional regulation of vasoactive intestinal peptide receptor - 1 (VPACR-1) in T lymphocytes.
Dr. Sheri Dorsam, research assistant professor of chemistry and molecular biology, serves as director of the NDSU Core Biology Facility. She completed her post-doctoral studies at the University of California at San Francisco and received her Ph.D. from Virginia Commonwealth University. Her research interests include transcriptional regulation and hematology. Dr. Dorsam's training includes cellular/molecular biology and cancer research.
Dr. Bin Guo, assistant professor, pharmaceutical sciences, has established a research program to study the regulation of cancer cell apoptosis. Human cells have a suicide mechanism that instructs cells when it is time to die. Defects in the regulation of this programmed cell death (also called apoptosis) will lead to diseases characterized by either too much cell death (such as Alzheimers and Parkinsons) or too little cell death (such as cancer). Dr. Guo studies the fundamental mechanisms of cell death regulation in cancer cells. He received his bachelor's degree from the University of Science and Technology of China and his Ph.D. from the State University of New York at Buffalo.
Dr. Jane Schuh, assistant professor of immunology, received her bachelor's and Ph.D. degrees from NDSU. Her research interests include biomedical significance of the initiation and maintenance of allergic asthma; the innate immune response in health and disease; murine models of human asthma; Aspergillus fumigatus-induced immune response.
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