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Faculty

Philip Williams, PhD

Philip Williams, PhD
  • Associate Member
    Natural Products and Experimental Therapeutics Program
    University of Hawaii Cancer Center
  • Academic Appointments

  • Professor
    Chemistry, College of Natural Sciences, University of Hawaii at Manoa

Degrees

  • PhD, Chemistry
    University of Hawaii at Manoa

Research Focus

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.

Selected Publications

  • Hughes RA, Zhang Y, Zhang R, Williams PG, Lindsey JS, Miller ES. Genome Sequence and Composition of a Tolyporphin-Producing Cyanobacterium-Microbial Community. Appl Environ Microbiol, Sept 15;83(19). pii:e01068-17. doi: 10.1128/AEM.01068-17. Print 2017 Oct 1. PubMed PMID: 28754701; PubMed Central PMCID: PMC5601333.
  • Parrish SM, Yoshida W, Yang B, Williams PG. (2017). Ulapualides C-E Isolated from a Hawaiian Hexabranchus sanguineus Egg Mass. J Nat Prod, Mar 24;80(3):726-730. doi: 10.1021/acs.jnatprod.6b00896. Epub 2017 Jan 18. PubMed PMID: 28098996; PubMed Central PMCID: PMC5365346.
  • Liang Z, Sulzmaier FJ, Yoshida WY, Kelly M, Ramos JW, Williams PG. (2015). Neopetrocyclamines A and B, polycyclic diamine alkaloids from the sponge Neopetrosia cf exigua. J Nat Prod; Mar 27;78(3):543-7. doi: 10.1021/np500759r. Epub 2015 Jan 13. PubMed PMID: 25585025; PubMed Central PMCID: PMC4380203.
  • Parrish SM, Yoshida WY, Kondratyuk TP, Park EJ, Pezzuto JM, Kelly M, Williams PG. (2014). Spongiapyridine and related spongians isolated from an Indonesian Spongia sp. J Nat Prod; Jul 25;77(7):1644-9. doi: 10.1021/np500256w. Epub 2014 Jul3. PubMed PMID: 24992702; PubMed Central PMCID: PMC4334272.

Publication list via PubMed

Active Grants

  • P. Williams, Principal Investigator
    1R01AG039468-01
    "Capture the Compound: Affinity Approaches to Secretase Inhibitors"
    April 1, 2011-March 31, 2015