BLACKSBURG, Va., April 19, 2012 – Researchers in the Nutritional Immunology and Molecular Medicine Laboratory (NIMML) at VBI have recently discovered a new compound that shows promise in ameliorating inflammation in the gut. Congruent to findings last year regarding abscisic acid, the discovery of Lanthionine Synthetase C-like protein 2 (LANCL2) as a novel therapeutic target could aid in relieving such diseases without the side effects of current medications. These findings have been reported in PloS ONE.
“The long-term goal of the NIMML is to elucidate the cellular and molecular mechanisms by which novel immune therapeutics ameliorate human diseases. Our integrated computer modeling and experimental validation approaches identified LANCL2 as a novel therapeutic target for infectious, immune-mediated and inflammatory diseases,” said Dr. Josep Bassaganya-Riera, Professor of Immunology, and the Director of the NIMML and the Center for Modeling Immunity to Enteric Pathogens (MIEP) at Virginia Tech.
Often the problem with current anti-inflammatory therapies is that they cause many side effects, including immunosuppression, delayed wound healing and gastrointestinal side effects such as ulcers or constipation.
“Using lessons learned from discoveries with the naturally occurring compound abscisic acid, NIMML has identified LANCL2 as a novel anti-inflammatory pathway. One compound associated with LANCL2, NSC61610, has shown great promise in suppressing gut inflammation. Our initial studies in mice indicate that the anti-inflammatory efficacy of NSC61610 depends on macrophage expression of peroxisome proliferator-activated receptor γ, a nuclear receptor downstream of the LANCL2 pathway and an internal thermostat for inflammation,” said Dr. Raquel Hontecillas, an Assistant Professor of Immunology at VBI and co-director of NIMML and Immunology Lead of MIEP at Virginia Tech.
Pharmaceutical companies employ the physical large-scale, high-throughput screening of thematic compound libraries against a therapeutic target to identify new drugs. This approach is very costly and it yields mixed results.
“NIMML has succeeded in the computational prediction of new ligands from large compound libraries by making use of structure-based virtual screening which is more cost-effective in drug discovery and provides reasonable hit rates. In this study, we used the structure of LANCL2 generated by homology modeling in a previous study from NIMML. Our findings indicate that virtual screening is an effective computational-based drug design method for discovering novel anti-inflammatory drug candidates,” said Pinyi Lu, a Ph.D. student in NIMML.
This study was supported by award number 5R01AT004308 of the National Center for Complementary and Alternative Medicine at the National Institutes of Health awarded to J.B.-R., NIAID Contract No. HHSN272201000056C to JBR and funds from the Nutritional Immunology and Molecular Medicine Laboratory.
About the Nutritional Immunology and Molecular Medicine Laboratory
The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) conducts translational research aimed at developing novel therapeutic and prophylactic approaches for modulating immune and inflammatory responses. The group combines computational modeling, bioinformatics approaches, pre-clinical experimentation and human clinical studies to better understand the mechanisms of immune regulation at mucosal surfaces and ultimately accelerate the development of novel treatments for infectious and immune-mediated diseases (www.nimml.org). In addition, the NIMML team leads the NIAID-funded Center for Modeling Immunity to Enteric Pathogens (www.modelingimmunity.org).
About the Virginia Bioinformatics Institute
The Virginia Bioinformatics Institute at Virginia Tech is a premier bioinformatics, computational biology, and systems biology research facility that uses transdisciplinary approaches to science, combining information technology, biology, and medicine. These approaches are used to interpret and apply vast amounts of biological data generated from basic research to some of today’s key challenges in the biomedical, environmental, and agricultural sciences. With more than 320 highly trained multidisciplinary, international personnel, research at the institute involves collaboration in diverse disciplines such as mathematics, computer science, biology, immunology, biochemistry, systems biology, statistics, economics, synthetic biology, and medicine. The large amounts of data generated by this approach are analyzed and interpreted to create new knowledge that is disseminated to the world’s scientific, governmental, and wider communities.
April 19, 2012