Immunometabolic Pathways

Landos has applied translational programs focused on immunity and metabolism to identify important, new molecular targets. Through advanced computational modeling-based predictions of immune cell differentiation, tissue-level cellular interactions and molecular signaling cascades, Landos has projected the ability of key targets, LANCL2 and NLRX1, to address multiple disorders linked to immune function.

The LANCL2 (Lanthionine Synthetase C-Like 2) pathway has a central role in metabolism and immune response in the context of immune-mediated diseases, including inflammatory bowel disease. LANCL2 activation supports the differentiation of T regulatory cells, increases the suppressive effects of T regulatory cells, and downregulates glycolytic pathways associated with TNF-alpha production. These multiple effects contrast with therapeutics that target a single immune function, such as TNF-alpha or JAK inhibition. In addition, Landos’ lead LANCL2-activating compound, BT-11, is designed to have a gut-restricted profile after oral administration, thereby avoiding adverse side effects of systemic immunosuppression.

NLR

The NLR (nucleotide-binding domain, leucine rich containing) family of proteins contributes to the regulation of innate and adaptive immunity. Landos has identified NLRX1 as a mitochondria-associated receptor with the ability to modulate immune responses linked to inflammatory bowel disease. The effects of NLRX1 activation include decreased differentiation of subpopulations of effector CD4+ T cells and increased mitochondrial metabolism in immune cells, resulting in decreased NF-kappa B activity and lower production of inflammatory cytokines. The development of the NLRX1 agonist has potential as a therapeutic mechanism of action for certain patient populations in need of an alternative, effective treatment or a component of a combination treatment.