What We Study

The Johnson Lab at Dominican University of California focuses on the discovery and medicinal chemistry of natural product compounds to search for:

1) therapeutic lead molecular structures to treat diseases in biomedical research

2) novel molecular probes in chemical biology research

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Some of the major chemotypes studied in our laboratory are the secondary metabolites isolated from the Indo Pacific marine sponge Cacospongia mycofijiensis which includes the latrunculin, mycothiazole, fijianolide (aka laulimalide), and zampanolide structural classes. Each of these chemotypes serve as potent (IC50 1~5 nM) therapeutic leads for treating cancer. They exhibit cytotoxicity to cancer cell lines by distinct mechanisms of action (MOA) which include: microfilament disruption (G-actin), mitochondria complex I inhibition, or microtubule stabilization. The mycothiazole, fijianolide, and zampanolide chemotypes have shown selective and or potent cytotoxicity to pancreatic and or triple negative breast cancers. The mycothiazole chemotype is also currently being investigated in our laboratory as a novel molecular probe to study the aging process in mitochondria.

 

Our laboratory is involved in large scale extraction, solvent partitioning, and scale up isolation of these and other pure compounds from repository extracts. Pure compounds are repurposed to undergo semi-synthetic medicinal chemistry efforts in order to optimize their molecular structures for development as new therapeutic leads and or molecular probes. We use advanced spectroscopic techniques such as high performance liquid chromatography (HPLC), followed by mass spectrometry (LCMS), as well as 1H, 13C, and 2D NMR to chemically validate and standardize our lead compounds for evaluation in collaborative bioassays. The interdisciplinary nature of our laboratory provides undergraduate and graduate students with diversified skill sets of knowledge in multiple aspects of biomedical and or chemical biology research.