DESCRIPTION OF THE PROJECT

The project is entitled “Discovery of Anticancer Agents of Diverse Natural Origin”, with A. Douglas Kinghorn, Ph.D., D.Sc. [Professor and Jack L. Beal Chair, The Ohio State University, OSU] serving as Principal Investigator:

 

Project 1 – Isolation Chemistry of Tropical Plants and Biological Evaluation (OSU; Project Leader, Dr. A. Douglas Kinghorn). Project 1 involves the isolation chemistry of bioactive

tropical plants to be collected by Project 2 (see below), inclusive of extraction, dereplication, compound purification, structure elucidation, and scale-up isolation stages. Recently, work has begun in screening U.S. coastal lichens and their fungal mycobionts (Dr. Liva Rakotondraibe). Biological screening is offered for Projects 1-3 using a selection of secondary cell-based and mechanism-based assays (Dr. Esperanza Carcache de Blanco).

 

Project 2 – Isolation Chemistry of Cultured Cyanobacteria and Plant Acquisition [University of Illinois at Chicago (UIC); Project Leader, Dr. Jimmy Orjala]. Project 2 entails cyanobacterial collection, culturing, genomic evaluation (Dr. Alessandra Eustaquio), extraction, dereplication, as well as plant collections from tropical rainforests (Dr. Djaja D. Soejarto). Extracts from the plants are further investigated in Project 1.

Example of Strains

Library of Cyanobacteria

Cyanobacteria occupy a unique phylogenetical position between bacteria and higher plants. Although being prokaryotic organisms they possess the ability of oxygenic photosynthesis. Like many microorganism, cyanobacteria can be grown in culture, but unlike most other microorganisms, cyanobacteria require light to grow. We have established a library of freshwater cyanobacteria in order to study the unique secondary metabolites that cyanobacteria produce. Our strain library currently contains over contained over 1200 freshwater cyanobacterial strains obtained from collections primarily from the Upper Midwest and Great Lakes Region. The strain collection is currently growing by more than 100 strains per year.

The phylum Cyanobacteria are comprised of phenotypically diverse organisms ranging from single-celled coccoid-shaped specimens to multicellular filaments comprised of differentiated cells. We are in the process of assessing the phylogenetic position of the strains in our library using the 16S rRNA sequence. We currently have taxonomic identification on over 300 strains. All 16S rRNA sequence data is made publicly available through NCBI.

Plant collection video

Project 3 – Isolation Chemistry of Filamentous Fungi and Biological Evaluation [University of North Carolina at Greensboro (UNCG); Project Leader, Dr. Nicholas H. Oberlies]. Project 3 works on new lead compounds from fungi obtained from Mycosynthetix Inc. (Hillsborough, NC; CEO/CSO Dr. Cedric Pearce), and comprises culturing, extraction, dereplication, compound purification, structure elucidation, scale-up isolation/yield optimization, and biosynthetic manipulation. Biological testing will be carried out at Columbia University as part of Project 3 (Dr. Brent Stockwell).

Core A – Biological Correlation and Analysis Core (UIC; Core Director, Dr. Joanna Burdette, assisted by Dr. Leslie Aldrich). Core A provides in vitro testing (screening assays using a small cancer cell line panel; HDAC and proteasome inhibition assays), for samples submitted by Projects 1-3. Promising compounds are evaluated mechanistically, and evaluated in mouse hollow fiber and xenograft bioassays.

Core B – Medicinal Chemistry and Pharmacokinetics Core (OSU; Core Director, Dr. James R. Fuchs). Core B conducts medicinal chemistry (synthesis/analogue development, SAR evaluation) and pharmacokinetic related functions (e.g., solubility, stability, formulation, metabolism, protein binding; supervised by Dr. Mitch A. Phelps) for selected compounds of promise from Projects 1-3. This core is new to the program project based on needs in medicinal chemistry and pharmacokinetics that were identified during the initial period of support.

Core C – Administrative and Biostatistics Core (OSU; Core Director, Dr. A. Douglas Kinghorn). Core C carries out overall administrative functions and offers biostatistics support (directed by Dr. Xiaoli Zhang) to Projects 1-3 and Cores A and B.