Project 1: Discovery of Cytotoxic Natural Products from Botanical Sources
The primary research project in the Still Lab is the use of diverse sources of botanical material, collaborative cytotoxicity screening and NMR-based organic structure analysis to discover bioactive chemistry from plants. The two core areas of this project include cytotoxicity screening and NMR-based organic structure analysis. The biological screening component involves a sulforhodamine B assay performed in the Still Lab at CSUDH and an expanded 19-human tumor cell line panel of Alamar Blue-based assays at local biotechnology company, Molecular Express, Inc., located 5 miles from CSUDH. This research project facilitates discovery of natural products from plants by involving undergraduate student researchers in both the Minority Biomedical Research Support (MBRS) and the Louis Stokes Alliances for Minority Participation (LSAMP) programs on the CSUDH campus.
Project 2: Discovery of Natural Product Inhibitors of Histone Demethylase from Botanical Sources
Plants produce a variety of structurally distinct chemical classes with proven utility against disease. A critical barrier to the progression of phytochemical research, however, is the vast number of plant species unexplored for novel bioactive compounds. The clinical success of histone deacetylase inhibitors such as romidepsin, a bicyclic depsipeptide natural product from Chromobacterium violaceum that is now FDA approved for treatment of cutaneous T-cell lymphoma, has stimulated work on the analogous demethylases (KDMs). An important development has been the inclusion of a KDM1 inhibitor into clinical trials for the treatment of small cell lung carcinoma and acute myeloid leukemia. The overarching goal of this project is to use diverse sources of botanical material to discover novel chemistry from plant extracts that are potential inhibitors of histone demethylase. There is a need for selective, potent demthylase inhibitors that are less toxic than the current repertoire of small molecule inhibitors. Harnessing the chemical scaffold diversity offered by plant species opens the window to unique drug combinations to improve inhibitory activity.
ORCID, Patrick Still: orcid.org/0000-0002-6773-7731
Selected publications in this area:
1. David M. Lucas, Patrick C. Still, Lynette Bueno Pérez, Michael R. Grever, and A. Douglas Kinghorn (2010). Potential of Plant-Derived Natural Products in the Treatment of Leukemia and Lymphoma. Current Drug Targets 11: 812-822. (Invited review article)
2. Yulin Ren, Min Wei, Patrick C. Still, Shunzong Yuan, Youcai Deng, Xiaozhuo Chen, Klaus Himmeldirk, A. Douglas Kinghorn, and Jianhua Yu (2012). Synthesis and Antitumor Activity of Ellagic Acid Peracetate. ACS Medicinal Chemistry Letters 3: 631-636.
3. Patrick C. Still, Bitna Yi, Ryan Pavlovicz, Tatiana F. González-Cestari, Li Pan, Hee-Byung Chai, Tran Hgoc Ninh, Djaja D. Soejarto, Chenglong Li, James R. Fuchs, Dennis McKay, and A. Douglas Kinghorn (2013). Alkaloids from Microcos paniculata L. With Cytotoxic and Nicotinic Receptor Antagonistic Activities. Journal of Natural Products 76: 243-249.
4. Lynette Bueno Pérez, Patrick C. Still, C. Benjamin Naman, Yulin Ren, Li Pan, Hee-Byung Chai, Esperanza J. Carcache de Blanco, Tran Ngoc Ninh, Bui Van Thanh, Steven M. Swanson, Djaja D. Soejarto, and A. Douglas Kinghorn (2014). Investigation of Vietnamese Plants for Potential Anticancer Agents. Phytochemistry Reviews 1-13.
5. Patrick C. Still, Tyler A. Johnson, and Phillip Crews (2014). Scrutinizing the Scaffolds of Marine Biosynthetics from Different Source Organisms: Gram-Negative Cultured Bacterial Products Enter Center Stage. Journal of Natural Products 77: 690-702. (Invited review article)
6. Christine M. Theodore, Nicholas Lorig-Roach, Patrick C. Still, Tyler A. Johnson, Joshua A. Schwochert, Marija Drašković, Cassandra N. Naphen, Mitchell S. Crews, Simone A. Barker, Steven L. Loveridge, Frederick A. Valeriote , Walter M. Bray, R. Scott Lokey, Hsiau W. Lee, and Phillip Crews. (2015). Biosynthetic Products from a Nearshore-Derived Gram-Negative Bacterium Enable Reassessment of the Kailuin Depsipeptides. Journal of Natural Products 78: 441-452.
7. Nicholas Lorig-Roach, Patrick C. Still, David Coppice, Jennifer E. Compton, Mitchell S. Crews, Gabriel Navarro, Karen Tenney, and Phillip Crews. (2017) Evaluating Nitrogen-Containing Biosynthetic Products Produced by Saltwater Culturing of Several California Littoral Zone Gram-Negative Bacteria. Journal of Natural Products 80: 2304-2310.