Philip Williams, PhD
- Associate Member
Natural Products and Experimental Therapeutics Program
University of Hawaii Cancer Center
- Associate Professor
Chemistry, College of Natural Sciences, University of Hawaii at Manoa
- PhD, Chemistry
University of Hawaii at Manoa
Many of the drugs currently used to treat cancer were developed based on naturally-occurring compounds in terrestrial plants and bacteria. Unfortunately, the discovery rates from these sources have slowed. New natural sources of drugs are needed. Despite the long history of drug discovery from natural sources, the marine environment is still relatively untapped. Covering 70% of the Earth's surface, the oceans contain all major phyla. The resulting intense competition for space and resources drives the evolution of specific and potent chemical defenses distinct from their terrestrial counterparts.
The research interests of Dr. Williams center on the discovery and evaluation of these small molecule chemical defenses from marine sources as potential drug leads. In collaboration with the other members of the Cancer Biology Program, marine extracts are screened against a variety of relevant cancer targets. The active constituents are then isolated using a combination of bioassay data and repeated separations. The structures of these metabolites are then determined primarily through the use of high-field NMR spectroscopy and chemical degradation. For example, Dr. Williams and colleagues have recently begun searching for novel inhibitors of the Ras/ERK MAP kinase pathway. Constitutive activation of this pathway is commonly observed approximately 30% of all tumor types and in 90% of all pancreatic tumors in epithelial tumors, hence it represents a potential therapeutic target. To this end, they have begun assaying extracts derived from marine sponges and cyanobacteria in an effort to discover new structural classes of inhibitors. Efforts in the Williams lab are directed towards identifying and characterizing these active components.
- Liang Z, Sorribas A, Sulzmaier FJ, JimĂ©nez JI, Wang X, Sauvage T, Yoshida WY, Wang G, Ramos JW, Williams PG. (2011). Stictamides A-C, 4-amino-3-hydroxy-4-phenylpentanoic acid containing MMP12 inhibitors. J Org Chem. May;20;76(10):3635-43. PMCID: PMC3733396.
- Rubio BR, Parrish SM, Schupp PJ, Schils T, Williams PG. (2010). Depsipeptides from a Guamanian Marine Cyanobacterium, Lyngbya bouillonii, with Selective Inhibition of Serine Proteases. Tetrahedron Lett,51, 6718-6721. PMCID: PMC2987581.
- Dai J, Jimenez JI, Kelly M, Williams PG. (2010). Dictazoles; Possible Vinyl Cyclobutane Biosynthetic Precursors to the Dictazolines. J Org Chem,75,2399-2402. PMCID: PMC2849972.
- Dai J, Jimenez J, Kelly M, Barnes S, Lorenzo P, Williams PG. (2008). Dictazolines A and B, Bisspiroimidazolidinones from the Marine Sponge Smenospongia cerebriformis. J Nat Prod,71(7),1287-1290. PMCID: PMC2573856.
Publication list via PubMed
- P. Williams, Principal Investigator
"Capture the Compound: Affinity Approaches to Secretase Inhibitors"
April 1, 2011-March 31, 2015