The Botanical Research Center at Memorial Sloan-Kettering Cancer Center will consist of a multidisciplinary collaborative team of senior scientists with laboratory and clinical expertise in each area required to reach our goal. The Center will pursue systematic investigation of five botanical supplements with previously described immunomodulatory activities (Echinacea, Astragalus, Turmeric, Maitake, and TJ-48 herbal formulation), addressing composition of the botanicals, mechanism of action, development of preclinical models, and translation to clinical application. The Center brings together leaders in basic science and clinical immunology, oncology, infectious diseases, botanicals, organic chemistry, and complementary medicine in four projects and two cores. Project by Livingston will study the effect of botanicals on the afferent arm of the immune system to determine how botanicals modulate antigen recognition and initiate immune response. Project by Cheung will address impact on the efferent arm to determine how botanicals enhance effector cell activity and molecular targets. Project by Pamer will investigate the integration of these two effects, determining their end result in the multi-compartment immune system via animal models of host response against infection. Project by Cassileth will address issues essential to human use: biomarkers and safety. The Administrative Core will coordinate research activities within the center, integrate research findings, and facilitate information exchange among research and advisory groups. The Botanical Core will authenticate and standardize study botanicals using genomic and chemical technology, fractionate botanical extracts to characterize constituents, and isolate active constituents for further study. It will aid preparation of study botanicals to meet FDA-level quality standards. Together, these projects encompass multiple dimensions of botanical immunomodulator research, addressing composition, mechanism, standardization and human biomarkers, and the full spectrum of host immune response, from molecular and cellular studies to animal and human research. We aim to advance the science and knowledge base of representative botanical immunomodulators, develop model experimental systems for botanical research, and generate evidence-based information to guide their human use.