Distinguished Professor Phil Crews

A primary goal of Phillip Crews’ marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isoA primary goal of Phillip Crews’ marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isolation assists us in the discovery of natural products potent against human diseases such as cancer or viruses. Our search for novel active compounds incorporates elements of structure elucidation but there are other dimensions to this research, including questions in the areas of chemical ecology, marine natural products biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy.

Whenever possible, we try to use new concise strategies to elucidate structures, including gradient 2D NMR techniques such as HMBC, HMQC, COSY, TOCSY, NOESY, and 1H-15N HMQC. Utilization of new NMR hardware, 3mm probes and advanced NMR microtubes, nanoprobe, micro-coil flow probe and cryo probe technology on 500 and 600 MHz machines addresses problems of limited amounts of sample. Another goal is to engage in follow-up studies that employ molecular mechanics data combined with these state-of-the-art NMR techniques.

The enduring focus of my lab is to expand fundamental knowledge about the novel structures and the bioactivity of marine natural products. The isolation and study of bioactive constituents from tropical sponges continues as a core interest. Discovery of marine-derived therapeutic leads or molecular probes has been successful. Examples of important achievements include: (a) our work on bengamide B that led to an anti-cancer Phase I clinical trial on a close analogue, and (b) promoting the international use of jasplakinolide as a molecular probe of actin biology. Nowadays, our campaign continues to identify privileged natural product derived structures and extend their impact. This is being accomplished through collaborations established with other academic and corporate scientists. The strategy of developing peak libraries for further screening has accelerated our discovery of novel compounds that are active against a variety of human diseases. Our library contains >20,000 of such wells. Sponges, gathered during expeditions to coral reefs throughout the world, are one beginning point for investigations and are housed in our repository of over 2,000 specimens. This repository also contains a collection of almost 1,500 pure compounds. The quest to explore the chemodiversity of microorganisms, especially those derived from sponges and CA coastal sediments, is in full swing. Our repository has some 2,000 marine sponge and sediment-derived microorganism strains. In addition, through joint projects with other groups, we are gaining insights on the makeup of sponge-derived microbial communities through molecular genetics studies. The path forward on developing access to important scaffolds produced by microorganisms involves three components. (a) We have considerable expertise in producing metabolites isolated from marine fungi and bacteria grown in salt-water culture. (b) We are beginning to probe the role of sponge associants that may be responsible for the actual biosynthesis of the compounds being isolated. We are making steady progress in developing culture strategies to mine sponge-derived bacteria that should be a source of new chemodiversity. (c) The close parallels in the structures we isolate from sponges versus those obtained from terrestrial myxobacteria is unexplainable. We now have the expertise to isolate marine derived strains of this underexplored group of Gram-negative organisms. We are beginning to add myxobacterium-derived compounds to our library. In summary, outcomes of our program include a large number of research publications, patents (US and worldwide), and significant molecular structures. Educating others is also important and my textbook Organic Structure Analysis (Edition 2) has become an important tool. Expanding the diversity of bioorganic chemistry professionals represents another goal and this continues through ongoing diversity oriented training grants that I direct.A primary goal of Phillip Crews’ marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isolation assists us in the discovery of natural products potent against human diseases such as cancer or viruses. Our search for novel active compounds incorporates elements of structure elucidation but there are other dimensions to this research, including questions in the areas of chemical ecology, marine natural products biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy.

Whenever possible, we try to use new concise strategies to elucidate structures, including gradient 2D NMR techniques such as HMBC, HMQC, COSY, TOCSY, NOESY, and 1H-15N HMQC. Utilization of new NMR hardware, 3mm probes and advanced NMR microtubes, nanoprobe, micro-coil flow probe and cryo probe technology on 500 and 600 MHz machines addresses problems of limited amounts of sample. Another goal is to engage in follow-up studies that employ molecular mechanics data combined with these state-of-the-art NMR techniques.

Lectures

Complete Biographical Sketch (October 1st, 2022)