Organic synthesis and chemical biology of small molecules
Dr. Sulikowski is Director of the CBI training program, which will ensure coordination between the two training programs. He has served as the Faculty Director of the VICB Synthesis Core since 2005, and was appointed Associate Director for Synthetic Chemistry and Deputy Director of the VICB in Spring 2011. He received his Ph.D. from the University of Pennsylvania under the mentorship of Amos B. Smith, III. He then pursued postdoctoral studies at Yale University under the sponsorship of Samuel J. Danishefsky with funding from an American Cancer Society research fellowship. His first faculty appointment was in the Department of Chemistry at Texas A&M University in 1991 where he rose through the ranks to Professor of Chemistry by 2001. He joined the Vanderbilt Chemistry Department as Professor of Chemistry and member of the VICB beginning with the 2004-2005 academic year. Dr. Sulikowski’s research areas are organic synthesis and chemical biology of small molecules, particularly natural products. Dr. Sulikowski serves as advisor to the Vanderbilt Specialized Chemistry Center of the NIH-sponsored Molecular Library Probe Center Network (MLPCN) and co-PI of the Vanderbilt Chemical Diversity Center of the NCI Chemical Biology Consortium (Experimental Therapeutics Program). He has served as director of the Vanderbilt CBI program since 2005 and co-PI of the Vanderbilt NSF-REU Summer Program in Chemical Biology. He has mentored over 35 graduate students and 15 postdoctoral associates during the course of 23 years as a faculty advisor. His current research group consists of 7 graduate students and 1 postdoctoral scholar.
Dr. Sulikowski has served as a member of the Study Section in Chemical & Bioanalytical Sciences at NIH and the Peer Review Committee for Cancer Drug Development of the American Cancer Society (2007-2010). Both panels review pre- and postdoctoral fellowship applications. He was also a member of the SBCA (Synthetic and Biological Chemistry) study section of the NIH (2009-2013). In 2011, he was appointed to serve on the Vanderbilt Chemical Physical Biology Program executive advisory board. He organized the 2005 10th International Conference on the Chemistry of Antibiotics and other Bioactive Compounds, and co-organized the 1st Regional Career Development Conference at the Chemistry Biology Interface.
Natural product total synthesis. We have maintained a longstanding interest in the development of synthetic strategies leading to the total synthesis of complex natural products. Historically, natural products present opportunities to address defined synthetic challenges presented in the novel structure of a natural product target. Currently we are pursuing the total synthesis of marine diterpenes (bielschowskysin) and alkylpiperidine alkaloids (upenamide and xestocyclamine A). These studies also serve as an excellent opportunity for the training of young scientists interested in the art and practice of chemical synthesis. Increasingly our motivation in the area of total synthesis is the biological study of synthetic products and derivatives (arachidonic acid metabolites and antimicrobial natural products).
Biology and chemistry of natural products. Natural products are among the most structurally complex and privileged of the bioactive small molecules. Analysis of the sources of small molecule drugs approved between 1981 and 2006 indicates that over half of the new chemical entities declared in this timeframe were natural products or derived from natural products. However, from the perspective of medicinal chemistry, the complex molecular architecture of natural products continues to pose a significant challenge to access not only quantities of the parent structure but also analogs to establish structure-activity relationships (SAR). In addition to utilizing our skills in chemical synthesis to access and modify natural products we also attempt to harness the biosynthetic machinery to access complex natural products, sometimes in collaboration with groups with expertise the genetic modification of biosynthetic pathways. We were the first group to identify the biosynthesis of the complex nonadrides CP-225,917 and CP-263,114 and study the development of this biosynthetic dimerization in the lab. More recently, working with the Bachmann group we have developed fluorescent derivatives the cell selective cytotoxic agent apoptolidin and demonstrated its localization in the mitochondria. We are also one of two groups in the world that developed a chemical synthesis of the microbial thiol bacillithiol, now being used by investigators worldwide.
Chemical probes and pre-clinical lead development. Phenotypic and functional screens of compound libraries are currently being used by a variety of biomedical investigators in Cell and Developmental Biology, Microbiology and Immunology and Pharmacology. We provide chemistry support in lead development and target identification studies. In some cases we have optimized lead potency and metabolic compound properties allowing animal studies to provide preliminary validation of new targets for therapeutic development.