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Lawrence Vernetti, PhD

Director of Early Drug Safety, Drug Discovery Institute, Associate Professor of Computational and Systems Biology

MS in Toxicology, University of Arizona
PhD in Pharmacology/Toxicology, University of Arizona

 

I spent the first part of my career as a study monitor at AbbVie (formerly Abbott Laboratories) conducting non- GLP and GLP compliant drug safety trials in mice, rats, dogs and non-human primates. During this time I wrote the IND toxicology summary sections for several compounds, including Ritonavir, which became the first approved protease inhibitor drug for HIV treatment. Later in my pharmaceutical experience, I initiated a screening program to assess candidate drugs for potential liability focusing on the use of mechanism-based measurements using High Content Screening (HCS) image analysis and in vitro liver models. In addition, I initiated a high throughput in vitro drug metabolism assay to rank order compounds by intrinsic clearance. 

After leaving Abbott Laboratories in 2007, I accepted the position of Director of Cellular Toxicology at Cellumen, in Pittsburgh, PA, a biotech developing an HCS-based predictive toxicology platform. During my tenure at Cellumen, I developed ‘scoring’ method to populate a drug safety database using an expert-based quantitative assessment of rodent and human adverse findings. The drug safety database eventually grew to over 500 marketed and failed drugs and became the core data set for collaborating computational scientists to train a safety risk predictive algorithm to identify toxic compounds from in vitro profile analysis. In December 2010, I joined the Drug Discovery Institute at University of Pittsburgh to initiate an early drug safety toxicology program. In these positions I used media measurements of liver products and HCS to read sub-cellular chemical fluorescent probes to interrogate pathways of toxicity activation. In 2012, I became an active participate into the development, validation and deployment of a physiologically relevant microfluidic, 3D, multicellular human liver microphysiology system (MPS). Our MPS model is a biomimetic re-construction of the liver sinusoid using 4 key liver cell types in a media flow-through device. In 2016, I worked with other scientists in the department to begin development of an MPS liver disease model to follow the progression of non-alcoholic fatty liver disease alone or as a part of metabolic syndrome including co-morbidity of type 2 diabetes. Additionally, I assisted in the design, use and interpretation of compound induced adverse effects for the BioSystics-AP™ (formerly known as the University of Pittsburgh MicroPhysiology Database), a commercial comprehensive platform constructed to design wet bench experiments, manage and analyze data for computational modeling to predict human toxicity, pharmacokinetics, drug efficacy and disease initiation and progression. 

 

Selected Publications 

  • Beaudoin JJ, Lara Clemens L, Miedel MT, Gough A, Zaidi F, Ramamoorthy P,  
    Wong K, Sarangarajan R, Battista C, Shoda LKM, Siler SQ, Taylor DL, Howell BA, Vernetti LA, Yang K. The combination of a human biomimetic liver microphysiology system with BIOLGXsym, a quantitative toxicology (QST) modeling platform for macromolecules, provides mechanistic understanding of Tocilizumab- and GGF2-induced liver injury.  Int J Mol Sci 2023, 24(11). 
  • Florentino RM, Morita K, Haep N, Motomura T, Diaz-Aragon R, Faccioli LAP, Collin de l'Hortet A, Cetin Z, Frau C, Vernetti L, Amler AK, Thomas A, Lam T, Kloke L, Takeishi K, Taylor DL, Fox IJ, Soto-Gutierrez A. Biofabrication of synthetic human liver tissue with advanced programmable functions. iScience. 2022;25(12):105503.  
  • Lefever D, Fen P, Miedel M, DiStefano J, DeBiasio R, Shun, TY, Vernetti L, Soto-Gutierrez A, Monga S, Bataller R, Behari J, Yechoor V; Bahar I, Gough A, Stern, A, Taylor D. A Quantitative Systems Pharmacology Platform Reveals Potential Repurposable Drugs for Nonalcoholic Fatty Liver Disease. Metabolites. 2022 Jun 7;12(6):528 
  • Courtney Sakolish; Yu-Syuan Luo; Alan Valdiviezo; Lawrence A. Vernetti; Ivan Rusyn. Prediction of Hepatic Drug Clearance with a Human Microfluidic Four-Cell Liver Acinus MicroPhysiology System. Toxicology. 2021 Nov;463:152954. 
  • Albert Gough, Alejandro Soto-Gutierrez, Lawrence Vernetti, Mo R. Ebrahimkhani, Andrew M. Stern, D. Lansing Taylor. Human biomimetic liver microphysiology systems in drug development and precision medicine. Nature Reviews Gastroenterol Hepatol, 2021 Apr;18(4):252-268. 
  • Vernetti LA, Senutovitch N, Boltz R, DeBiasio R, Shun TY, Gough A, Taylor DL. A human liver microphysiology platform for investigating physiology, drug safety, and disease models. Exp Biol Med (Maywood). 2016 Jan;241(1):101-14. 

 

 

Primary Address
700 Technology Dr Pittsburgh PA 15219
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