Hendrik Luesch, Ph.D.

Hendrik Luesch, Ph.D., a professor of medicinal chemistry, received his Diplom in Chemistry at the University of Siegen (Germany) in 1997. He studied marine natural products chemistry at the University of Hawaii at Manoa and obtained his Ph.D. with Professor Richard E. Moore in 2002. He undertook three years of postdoctoral studies as an Irving S. Sigal Fellow at The Scripps Research Institute with Professor Peter G. Schultz in functional genomics and chemical biology. In 2005 he joined the faculty of the Department of Medicinal Chemistry at the University of Florida (UF) as an assistant professor and was tenured and promoted to associate professor in 2010 and to full professor in 2015. He holds the endowed Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development and serves as Department Chair. He combines his interest in marine natural products chemistry with genomics and proteomics approaches for the discovery and characterization of potential drugs and molecular drug targets. Specifically, he leads a multidisciplinary marine natural products program that integrates genome mining, isolation, chemical synthesis, pharmacology, mechanism of action and early development studies. He is founding Director of UF’s Center for Natural Products, Drug Discovery and Development (CNPD3). He has published over 160 papers, is inventor on 40 issued patents (US, PCT and nationalized) and cofounded companies, consistent with the translational nature of his research and entrepreneurial mindset. He has received the UF Technology Innovator Award for several years. He has been invited to prestigious national and international meetings and has presented at institutions around the world (over 140 invited lectures). He serves as Commissioning Editor and Editorial Board member of Natural Product Reports, the most prestigious and highest ranked journal in the field, and on the Editorial Board of Marine Drugs.

Dr. Luesch‘s multidisciplinary research program at the interface of chemistry and biology combines classical natural products chemistry with high-throughput screening and chemical genomics. It involves most aspects of drug discovery ranging from the collection of promising marine organisms, bioassay development, NMR spectroscopic structure determination, chemical synthesis, mechanism-of-action studies, and pharmacology, up to the preclinical and clinical development of candidate molecules. His lab is producing a small but increasing pipeline of bioactive compounds that are at various developmental stages. Recent incorporation of upstream genome mining, biosynthetic gene cluster identification, and heterologous expression led to a concerted “Genomes to Natural Products to Drugs” initiative in the CNPD3.

His lab has been working closely with chemical ecologist Valerie Paul, Ph.D. (Smithsonian Marine Station) and discovered numerous novel bioactive compounds from marine sources, particularly cyanobacteria, as starting points for drug discovery and development. He discovered the potent microtubule-destabilizer dolastatin 10 from a marine cyanobacterium. Dolastatin 10 has provided the basis for three marketed anticancer drugs to date. Antibody-drug conjugates (ADCs) of a dolastatin 10 analogue have been FDA approved for Hodgkin’s lymphoma and anaplastic large cell lymphoma (brentuximab vedotin), B-cell lymphoma (polatuzumab vedotin), and refractory bladder cancer (enfortumab vedotin). His team discovered a new chemical scaffold from marine cyanobacteria, gatorbulin-1, that targets a new tubulin pharmacological site. He reported the entire spectrum of the discovered chemical and biological novelties, including the isolation, structure determination, chemical synthesis, mechanism of action, target identification, and binding mode elucidation at the atomic level. His team discovered, synthesized and performed the in vitro and in vivo evaluation as well as preclinical developmental studies for largazole, one of the most potent class I histone deacetylase (HDAC) inhibitors. He discovered apratoxins and subsequently characterized the novel mechanism of action through genomic and proteomic approaches, revealing that this class of natural products inhibits cotranslational translocation in the secretory pathway. Medicinal chemistry efforts paved the way for the development of synthetic apratoxins for pancreatic and colon cancer as well as retinal angiogenic diseases. His team also discovered, synthesized and tuned selectivity profiles of protease inhibitors, GPCR modulators, cytoskelectal and cell membrane targeting agents, as well as many other natural products with various functions. In general, his team puts significant biology behind all discoveries to enhance the value of the natural products and to enable the best chances for development. He discovered approximately 200 natural products belonging to over 50 chemical scaffolds.

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