Dr. Wiseman has 30 years of experience in drug discovery research in the pharmaceutical industry. He recently joined Edelweiss Connect as Senior Fellow in the team that is building computational tools to promote multiple facets of chemical safety – including toxicology, low environmental impact, and green manufacturing - in multiple industries. He previously held positions as worldwide vice president and member of the Research Executive Council of the pharmaceutical company GlaxoSmithKline and then as Chief Technology Officer at the biotechnology company Locus Pharmaceuticals. At Locus he participated in raising $32 MM in financing and established research collaborations valued at $60 MM. Most recently, he served for 10 years as Executive in Residence, Senior Research Scientist, and Adjunct Professor of Chemistry and Biochemistry at Ohio University. In these roles he conducted independent research on natural products as therapeutic agents and was responsible for identifying and advancing life science technologies to commercialization. These efforts advanced 5 companies to the pre-seed funding stage. Dr. Wiseman holds a B.S. degree summa cum laude in chemistry from Ohio University and a Ph.D. in chemistry from Harvard University, with postdoctoral studies in biochemistry at Stanford and Brandeis Universities. He retired from Ohio University in 2022.
Evaluating Membrane Disruption as a Cause of Steatosis: Suitability of Existing Data and Opportunities for Additional Studies.
Non-alcoholic hepatic steatosis represents an imbalance between lipid uptake, synthesis, and oxidation. Since the nuclear hormone receptors are key regulators of these processes, a biochemical analysis predicts that modulators of specific nuclear hormones or specific enzymes of lipid metabolism will induce steatosis, and this is demonstrably the case. However, for highly prevalent conditions such as steatosis, it is also reasonable to propose that more promiscuous mechanisms are a major underlying cause. The purpose of this study was to test the hypothesis that membrane disruption is a major cause of steatosis. The secondary purpose was to evaluate the suitability of major repositories of toxicity data for testing this hypothesis. These are the AOP-Wiki, which is a manually constructed repository of biochemical pathways leading to toxicity; the AOP-Database, which holds the results of toxicity-related high-throughput assays from the U.S. EPA ToxCast program; and the InXight database, which holds clinical data for drugs, drug precursors, and drug metabolites. The results show a strong correlation between membrane disruption and steatosis when compared to other potential causes. However, the results also point out opportunities to extend the current data to fully understand this relation. For example, if membrane disruption is a cause of steatosis and not just a correlation, the available data does not illuminate the specific biochemical steps that lead from this initiating event to steatosis. In addition, further studies would benefit from a facile screening assay for membrane disruption that can be applied prospectively.