PhD in Biology/Biophysics, Carnegie Mellon University

I received my PhD in Biophysics from Carnegie Mellon University where I developed tools and assays using fluorescence microscopy to study single cell physiology. As a Postdoc I served as the Director of Imaging Technology in the Center for Light Microscope Imaging and Biotechnology at Carnegie Mellon University, an NSF funded Science and Technology Center. I later joined Cellomics, to automate light microscopy and enable the analysis of millions of cells under thousands of experimental conditions in a single day, an approach we named HCS. I led the team which developed the first HCS platform, including the HCS Store Database, and the following generation of HCS platforms. In 2005, I joined Cellumen with a mission to develop Cellular Systems Biology (CSB) assay panels, using HCS Technology. The goal was to build better predictive models of in vivo toxicity using CSB data from in vitro assay panels. I led the development of classification models to interpret the multiparameter data generated for large pharmaceutical companies, the FDA and the EPA. Cellumen was acquired In 2010 and I joined the University of Pittsburgh Drug Discovery Institute. Presently my research is focused in 3 areas. First, is the development of, and computational analysis of data from, 3D tissue models in microfluidic devices (i.e. microphysiology systems, MPS). We have developed multiple 3D human liver MPS that use reporter cells (sentinels), fluorescent reagents, and probes for direct functional readouts. Analyses of a broad array of real-time and off-line biochemical, mass spectrometric, and high content assays are used to profile functional effects and to develop predictive models. We have used these MPS’ to model NAFLD, Type 2 diabetes, a melanoma niche, and other liver disease states. Second, is the design and development of the Microphysiology Systems database (MPS-Db) and website, now known as the BioSystics-Analytics Platform™ (BioSystics-AP™). The BioSystics-AP is designed to streamline the workflow for MPS, and therefore is expected to accelerate the application of MPS technologies by Pharma, and in the clinic. Third, is the application of informatics and machine learning to multiparameter phenotypic profiles. This approach to the interpretation of these complex data sets was used to develop a predictive model of liver toxicology and is the basis for a patent on its application to pathology imaging, and has also been applied to studying the relationship between cellular heterogeneity, compound mechanism(s) of action and cell signaling pathways. 

Selected Publications 

•  Lefever DE, Miedel MT, Pei F, DiStefano JK, Debiasio R, Shun TY, Saydmohammed M, Chikina M, Vernetti LA, Soto-Gutierrez A, Monga SP, Bataller R, Behari J, Yechoor VK, Bahar I, Gough A, Stern AM, Taylor DL. A Quantitative Systems Pharmacology Platform Reveals NAFLD Pathophysiological States and Targeting Strategies. Metabolites. 2022;12(6). Epub 2022/06/24. doi: 10.3390/metabo12060528. PubMed PMID: 35736460. 
• Saydmohammed M, Jha A, Mahajan V, Gavlock D, Shun TY, DeBiasio R, Lefever D, Li X, Reese C, Kershaw EE, Yechoor V, Behari J, Soto-Gutierrez A, Vernetti L, Stern A, Gough A, Miedel MT, Lansing Taylor D. Supplement to Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors. Experimental biology and medicine. 2021;246(22):2420-41. Epub 2021/05/08. doi: 10.1177/15353702211009228. PubMed PMID: 33957803. 
• Sakolish C, Reese CE, Luo YS, Valdiviezo A, Schurdak ME, Gough A, Taylor DL, Chiu WA, Vernetti LA, Rusyn I. Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS). Toxicology. 2021;448:152651. Epub 2020/12/12. doi: 10.1016/j.tox.2020.152651. PubMed PMID: 33307106.  
• Bircsak KM, DeBiasio R, Miedel M, Alsebahi A, Reddinger R, Saleh A, Shun T, Vernetti LA, Gough A. A 3D microfluidic liver model for high throughput compound toxicity screening in the OrganoPlate®. Toxicology. 2021;450:152667. Epub 2020/12/29. PubMed PMID: 33359578. 
• Schurdak M, Vernetti L, Bergenthal L, Wolter QK, Shun TY, Karcher S, Taylor DL, Gough A. Applications of the microphysiology systems database for experimental ADME-Tox and disease models. Lab on a chip. 2020;20(8):1472-92. Epub 2020/03/27. doi: 10.1039/c9lc01047e. PubMed PMID: 32211684. 
• Nmezi B, Vollmer LL, Shun TY, Gough A, Rolyan H, Liu F, Jia Y, Padiath QS, Vogt A. Development and Optimization of a High-Content Analysis Platform to Identify Suppressors of Lamin B1 Overexpression as a Therapeutic Strategy for Autosomal Dominant Leukodystrophy. SLAS Discov. 2020;25(8):939-49. Epub 2020/05/01. PubMed PMID: 32349647. 
• Miedel MT, Gavlock DC, Jia S, Gough A, Taylor DL, Stern AM. Modeling the Effect of the Metastatic Microenvironment on Phenotypes Conferred by Estrogen Receptor Mutations Using a Human Liver Microphysiological System. Scientific reports. 2019;9(1):8341. Epub 2019/06/07. PubMed PMID: 31171849. 
• Li X, George SM, Vernetti L, Gough AH, Taylor DL. A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX. Lab on a chip. 2018;18:2614-31. PubMed PMID: 30063238. 
• Lee-Montiel FT, George SM, Gough AH, Sharma AD, Wu J, DeBiasio R, Vernetti LA, Taylor DL. Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems. Experimental biology and medicine. 2017;242(16):1617-32. Epub 2017/04/15. PubMed PMID: 28409533.