Dr. William Gerwick: Marine Natural Products Drug Discovery and Biosynthesis

Research Summary: Marine Natural Products Drug Discovery

Dr. Gerwick’s research focuses on exploring the unique natural products of marine algae and cyanobacteria for useful biomedical properties. These chemically prolific organisms are sources of numerous highly unusual metabolites, and the Gerwick group has been involved in their discovery and evaluation in the areas of cancer, inflammation, infectious disease including tropical diseases such as malaria and leishmaniasis, neurochemical pathways, as well as agricultural uses. The Gerwick group has also examined the pathways of biosynthesis of many of the compounds they have discovered over the years, and pioneered the characterization of their origins at the molecular genetic and genomic levels. More recently, his group has also applied their chemical and genetic approaches to the goal of obtaining biofuels from cultured microalgae.

Dr. Gerwick’s group uses SCUBA to collect marine samples from around the world, such as Panama, Madagascar and Papua New Guinea, and grows many of these life forms in the laboratory in La Jolla.
Extracts of these organisms are tested for bioactivity, and the active compounds are isolated and structures defined using nuclear magnetic resonance (NMR) and mass spectrometry (MS). Highly interesting metabolites are developed through collaboration with academic and industrial researchers, and biosynthetic pathways determined using gene cloning and other molecular biological methods.

Academic Achievements

Education: B.S. in Biochemistry (1976) UC Davis; Ph.D. in Oceanography (1981) Scripps Institution of Oceanography, UCSD; Postdoctoral Microbial Biosynthesis Natural Products (1981-82) UConn.

Awards and Honors: Fogarty Senior International Research Fellowship, NIH (1990-91); Associate Editor for the Journal of Natural Products Chemistry (2001- 08); Member, NIH Study Section on Bioorganic and Natural Products Chemistry (2003-07); Fellow, American Society of Pharmacognosy (2008).

Leadership Experience: Deputy Director, Marine Freshwater Biomedical Center, Oregon State University, Corvallis, OR (1998-2005); President of the American Society of Pharmacognosy (2002-03); Principle Investigator, Panama International Cooperative Biodiversity Group (2003–2013).

Teaching

• Pharmacy: Contemporary Topics in Pharmacology (SSPPS 218A) (CourseMaster).
• Pharmaceutical Chemistry (SSPPS 221).
• Pharmaceutical Biochemistry (SSPPS 223).
• Scripps: Marine Natural Products Chemistry (SIO 264).
• Seminar in Marine Chemical Biology (SIO 262).
• Marine Biotechnology (SIO 242).

Key Contributions to Pharmaceutical Sciences

• Revealed marine algae as rich sources of structurally novel eicosanoids related to human prostaglandins and leukotrienes.
• Discovered and determined the structure and properties of several promising anticancer agents, such as curacin A, from marine cyanobacteria.
• Discovery of structurally novel neurotoxins from marine cyanobacteria and characterization of their mechanisms of action.
• Characterized the biosynthesis of important pharmaceutical leads from marine cyanobacteria at the chemical, biochemical and genetic levels.

Selected Recent Publications (from 245 peer-reviewed articles)

Gu et al. (2009). Metamorphic enzyme assembly in polyketide diversification. Nature. 459:731-735.

Pereira et al. (2009). a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria. Chemistry & Biology 16:893-906.

Leão et al (2010). “Synergistic allelochemicals from a freshwater cyanobacterium”, Proc. Natl. Acad. Sci. 107:11183-8.

Tidgewell et al (2010). “Evolved Diversification of a Modular Natural Product Pathway: Production of Apratoxins F and G, Two Cytotoxic Cyclic Depsipeptides from a Palmyra Collection of Lyngbya bouillonii”, ChemBioChem 11:1458-1466.

Potential Collaborative Programs with the Pharmaceutical Industry

• More than thirty years experience in drug discovery from natural products, focusing on marine natural products.
• Exploring and developing the genetic potential of marine organisms to yield new compounds, enzymes and genes for biotechnology.