Title: Verticillins and Wheldone: Two leads from different chapters of the drug discovery story

Abstract:

Fungal metabolites are well known for providing humanity with medical benefits, with penicillin and the antibiotics revolution that it stimulated probably the greatest example from the 20th century. Our team has been studying fungi for drug leads effective in the fight against cancer, with an emphasis on ovarian cancer, and this presentation will peer into two different chapters of that ongoing story. The verticillins are potent, cytotoxic leads, first discovered over 50 years ago. Our emphasis has been on amplifying their supply, generating semisynthetic analogues, understanding their mechanism of action, and optimizing their delivery. In contrast, wheldone is a molecule that we first described recently. Interestingly, it is only biosynthesized via the antagonism of two fungi fighting for limited resources in co-culture. We’ve spent considerable effort developing ways to supply this compound on a larger scale, as the scale up of fungal co-cultures is not discussed in the literature. We’ve also probed its mode of action and are starting to generate semisynthetic analogues. In sum total, this presentation will provide a glimpse into how natural products drug discovery from fungi is carried out in the modern research setting.

Bio: 

Nicholas Oberlies received his B.S. in Chemistry from Miami University (Oxford, Ohio) in 1992 and his Ph.D. in Medicinal Chemistry and Pharmacognosy from Purdue University (West Lafayette, Indiana) in 1997, where he studied under Professor Jerry L. McLaughlin. He then spent a year as a postdoctoral chemist at American Cyanamid (Princeton, New Jersey), where he investigated leads with insecticidal, herbicidal, and fungicidal properties from natural sources. In 1998, he joined the Natural Products Laboratory at Research Triangle Institute (RTI) in North Carolina, specifically to be mentored by the late Dr. Mansukh C. Wani and the late Dr. Monroe E. Wall, who are most well known as the co-discoverers of taxol and camptothecin. He rose progressively through the ranks of RTI and eventually directed the Natural Products Laboratory. In 2009, he moved his research group to the Department of Chemistry and Biochemistry at the University of North Carolina at Greensboro. 

He has received several awards that speak to his accomplishments, including the Matt Suffness Young Investigator Award from the American Society of Pharmacognosy, the 40 under 40 Leadership Award from the Triangle Business Journal, and the North Carolina Distinguished Speaker Award from the NC Section of the American Chemical Society. 

He is a Fellow and Past President of the American Society of Pharmacognosy.