Research


Natural Product Sources

Fungi
Estimates suggest that several million fungi inhabit our planet, yet only a fraction of these species have been described (let alone examined for secondary metabolites). This situation presents a unique and exciting opportunity to identify novel organic compounds made by fungi that are capable of improving human health. We obtain fungi from a wide variety of substrates including soils, plants, sediments, insects, and animals. The breadth of samples we examine for fungi has expanded greatly thanks in large part to the participation of our citizen team of citizen scientists. Once in the lab, our group uses a diverse set of media and culture conditions to encourage the growth of new and/or uncommon fungal species. Our microbial collection consists of over 10,000 isolates obtained from samples collected across the United States. All of these fungi have been grown in the lab and extracts prepared that contain their unique secondary metabolites. We and our collaborators use this one-of-a-kind resource in combination with biological assays to identify new bioactive compounds that have promising drug-like activities. Researchers interested in screening compounds and extracts from our library should contact the director for more information.

Bacteria
Bacteria grow in nearly every conceivable environment on earth. One group of microbes that are of considerable interest to our laboratory is the consortium of bacteria that reside in and on mammals. We have explored bacteria from the human mouth and recently expanded this to include bacteria from other mammalian sources. We employ an opportunistic sampling approach for obtaining bacteria from wild mammalian sources. This method focuses on sampling ‘fresh’ road kill from local highways. The carcasses of recently deceased mammals are a virtual microbial treasure trove containing thousands of bacteria, many of which are new to science.

Disease Targets

Cancer
Cancers of all kinds continue to plague humans. Although important inroads to success have emerged, there are still many types of cancer that are virtually untreatable and/or have a high mortality rate. Historically, natural products have played a tremendous role in the development of therapies for treating cancers and we believe that the scientific community has only just scratched the surface when it comes to mining this resource for new cancer-fighting compounds. We are particularly interested in the development of targeted therapies for difficult-to-treat or yet untreatable cancers including childhood cancers, pancreatic cancers, triple negative breast cancers, and glioblastomas. Our approach to addressing these therapeutic needs involves the use of innovative methods for screening and testing natural products in phenotype-driven assays that highlight the unique genomic defects within each cancer subtype. This targeted approach is beginning to yield compounds with promising activity profiles, as well as providing insights into the molecular targets suitable for inhibiting cancers of diverse origins.

Microbial Infections
We are using our natural products library to identify compounds active against a range of deadly infectious bacteria and fungi including Acinetobacter spp., methicillin-resistant Staphylococcus aureus, Candida spp., Enterobacter spp., Aspergillus spp., and others. We utlize assays geared toward uncovering natural products that could be used to combat persistent bacterial and fungal infections such as those caused by recurring and antibiotic-resistant microorganisms. Two ways that we have approached this problem are through the inhibition of biofilms, as well as synergistic enhancement of antibiotic activities.

Parasitic Diseases
We are in the process of completing preliminary studies that will enable our group to screen for new compounds that inhibit a variety of human parasites. These tests will be completed in early 2014 and further details are expected to be released later this year.

Collaborative Studies

Making meaningful inroads to the discovery of new drugs requires cross-disciplinary groups of researchers. Our research group consists of students, postdoctoral fellows, and researchers with diverse expertise in chemistry, natural products, biology, and microbiology. In addition, we are proud to have strong collaborative relationships with researchers in the Institute for Natural Products Applications and Research Technologies (INPART), as well as outside of the University of Oklahoma. We routinely work with experts in the fields of mycology (Andrew Miller), medicinal chemistry (Doug Frantz), cancer pharmacology (Susan Mooberry and April Risinger), freshwater ecology (Mark Luttenton), and microbiology (Brad Stevenson).