PO1 Anticancer Project Grant
Discovery of Anticancer Agents of Diverse Natural Origin
Welcome to our website. We are a consortium of investigators located in several institutions, whose common goal is the discovery of anticancer agents from the world�s biodiversity. Our biodiversity focus embraces terrestrial plants, but heavily focused on the seed plants, the terrestrial and marine cyanobacteria, and the fungal biodiversity.
This Program Project Group (PPG) is based at the Ohio State University (OSU) and is headed by Prof. A.D. Kinghorn, who serves as the Principal Investigator (Project Director). The following member institutions make up the PPG consortium: The Ohio State University (OSU) � the primary seat of the project -, the University of Illinois at Chicago (UIC), Research Triangle Institute (RTI), University of North Carolina at Greensboro, Mycosynthetix, North Carolina Central University, and an industrial partner, Bristol-Myers Squibb (B-MS). The group possesses a combined vast experience in the isolation, structure elucidation, and biological evaluation of natural products, to develop a consolidated, integrated program for the discovery of novel anticancer agents of diverse origin for development as cancer chemotherapeutic agents.
In this project, plant materials are sourced from select tropical countries under established principle of ABS (access and benefit-sharing), with a goal to maximize taxonomic diversity, and are collected by established collaborating botanists located in each country, through the guidance of the NAPRALERT database.All voucher herbarium specimens of terrestrial plants studied are in deposit in the home country of the collaborating institutions, at the John G. Searle Herbarium (F) of the Field Museum in Chicago � the botanical base of the PO1 research, and at a number of collaborating botanical institutions, within the US and overseas.
Cyanobacteria and filamentous fungi are also sourced under established principle of ABS through the collaboration of scientists in select countries, and voucher specimens are also in deposit at the collaborating institutions, in the US and overseas.
Cyanobacteria and filamentous fungi are also sourced under established principle of ABS through the collaboration of scientists in select countries.
Organisms acquired are extracted and evaluated in a diverse battery of relevant mechanism-based, cell-based, and tumor-growth related assays currently operational at OSU, UIC, RTI, and B-MS (Projects 1-3; Cores A and B).
Dereplication of known active compounds is accomplished at OSU, UIC, and RTI using computerized literature surveys and LC-MS coupled to bioassays.
Bioassay-directed fractionation is employed (OSU, UIC, RTI; Projects 1-3, respectively) for the elucidation of active principles. Lead development of active natural products via medicinal chemistry is conducted at OSU (Project 1). Novel, active compounds thus discovered are further evaluated in our panel of in vitro and in vivo bioassays (Projects 1 and 3, Cores A and B), as well as for efficacy in chronic lymphocytic leukemia cells. Group decisions are made regarding the further development of agents for potential use as anticancer agents.
The more advanced states of biological and toxicological testing, as well as the procurement of larger quantities of lead compounds are sponsored by B-MS (Core B).
The Consortium also works with the involvement of the NCI Program Director in the discovery process, and holds regular meetings of key scientific personnel (inclusive of our External Advisory Panel) to enhance communication and decision-making processes.
This Project Is Funded Through NIH Grant 1-P01-CA125066