I am an Assistant Professor at the Drug Discovery Institute at the University of Pittsburgh. The goal of my research is to use all-human structured biomimetic liver microphysiology systems (MPS) to model both normal and disease-state liver physiology. My main interests are in coupling the use of quantitative systems pharmacology (QSP) and liver MPS as a precision medicine platform to provide new mechanistic detail and predict and/or initiate the development of novel therapeutics for NAFLD/NASH as well as to use liver MPS models to examine the impact of the liver tumor microenvironment on metastatic phenotypes that are associated with the progression of different cancer types (metastatic melanoma and breast cancer). I have a broad background in cell biology, with specific training and expertise in key research areas complementary to the goals of this proposal, including implementation of liver-on-a-chip model systems as disease models, drug discovery using MPS, fluorescence-based imaging techniques, and the optimization and standardization of liver MPS platforms.
Selected Publications:
- Lefever DE, Miedel MT*, et al. A Quantitative Systems Pharmacology Platform Reveals NAFLD Pathophysiological States and Targeting Strategies. Metabolites. 2022 Jun 7;12(6):528. doi: 10.3390/metabo12060528. PMID: 35736460; PMCID: PMC9227696. [* joint first author].
- 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. Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors. Exp Biol Med (Maywood). 2021 Nov;246(22):2420-2441. doi: 10.1177/15353702211009228. Epub 2021 May 6. PMID: 33957803; PMCID: PMC8606957.
- 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. Sci Rep. 2019 Jun 6;9(1):8341. doi: 10.1038/s41598-019-44756-5. PMID: 31171849; PMCID: PMC6554298.
- 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 Feb 28; 450:152667. doi: 10.1016/j.tox.2020.152667. Epub 2021 Jan 6. PMID: 33359578.