Our research lies at the interface of chemistry and biology of bioactive natural products. Our group (along with our biological collaborators) is the worldwide leader in the study of natural products OSW-1 and superstolide A. Innovative synthetic methodologies and strategies were developed and applied to the syntheses of these natural products and their analogs. Our efficient synthetic approaches have successfully solved their bottleneck of supply and provided biologists a sufficient amount of materials for biological investigation. Our medicinal chemistry study has resulted in defining their minimum pharmacophores and the synthesis of two groups of “patent-protected late stage drug candidates” with improved ADMET profiles that have successfully advanced to preclinical stage and have the potential to be 1st-in-class. Our synthetic approaches can also be modified for the synthesis of innovative molecular probes for the identification of their drug targets and the elucidation of their mechanisms of action. In addition, inspired by these natural products we have successfully designed and developed the new generation of cytotoxic payloads with novel mechanisms of action for antibody-drug conjugates (ADCs), small-molecule drug conjugates (SMDCs) including peptide-drug conjugates (PDCs) and aptamer-drug conjugates (ApDCs) for cancer therapy. Furthermore, our innovative research programs have provided excellent training for graduate students and postdoc fellows who now work either in academia or in the pharmaceutical industry including Merck, Novartis and AstraZeneca.