Background
Research Focus
Our lab uses microfluidics and 3D scaffolds to create physiologically realistic cell culture models of organs and tissues. These in vitro models can be engineered to signal cells using biochemical and biomechanical pathways, help to minimize animal testing, and provide tightly controlled, reproducible experimental conditions. The goal of our work is to replicate some of the cell-cell and cell-extracellular matrix interactions not easily studied in vivo or in silico to better understand how cells behave during disease and respond to chemicals or drugs. Our current research has applications toward cardiovascular disease and cancer and focuses on how disruptions in a tissue's local mechanical environment can lead to changes in cell phenotype and disease initiation and progression.
Selected Recent Publications
Complete List of Publications:
1. Liu Y, Rogel N, Harada K, Jarett L, Maiorana CH, German GK, Mahler GJ, Doiron AL. Nanoparticle size-specific actin rearrangement and barrier dysfunction of endothelial cells. Nanotoxicology. 2017. doi: 10.1080/17435390.2017. PMID: 28885066.
2. Mina SG, Huang P, Murray BT, and Mahler GJ. The role of shear stress and altered tissue properties on endothelial to mesenchymal transformation and tumor-endothelial cell interaction. Biomicrofluidics. 2017; 11(4): 044104. doi: 10.1063/1.49917. PMID: 28798857.
2. Dahal S, Huang P, Murray B, and Mahler GJ. Endothelial to mesenchymal transformation is induced by altered extracellular matrix in aortic valve endothelial cells. Journal of Biomedical Materials Research: Part A. 2017. doi: 10.1002/jbm.a.36133. PMID: 28589644.
3. Guo Z, Martucci NJ, Moreno Olivas F, Tako E, Mahler GJ. Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine. Nanoimpact. 2017; 5: 70-82. doi:10.1016/j.impact.2017.01.002.
4. Sakolish CM and Mahler GJ. A novel microfluidic device to model the human proximal tubule and glomerulus. RSC Advances. 2017; 7: 4216 – 4225. doi: 10.1039/c6ra25641d.
5. Mahler GJ, Esch MB, Stokol T, Hickman JJ, Shuler ML. Body-on-a-chip systems for animal-free toxicity testing. ALTA. 2016; 44(5):469-478. PMID: 27805830.
6. Mina S, Wang W, Qao Q, Huang P, Murray BT, Mahler GJ. Shear stress magnitude and transforming growth factor-β1 regulate endothelial to mesenchymal transformation in a three dimensional culture microfluidic device. RSC Advances. 2016; 6: 85457 – 85467. doi: 10.1039/C6RA16607E.
7. Sakolish CM, Esch MB, Hickman JJ, Shuler ML, Mahler GJ. Modeling barrier tissues in vitro: Methods, achievements, and challenges. EBioMedicine. 2016; 5: 30–39, doi: 10.1016/j.ebiom.2016.02.023. PMID: 27077109.
8. Pardo YA, Florez C, Baker KM, Schertzer JW, Mahler GJ. Detection of outer membrane vesicles in Synechocystis PCC 6803. FEMS Microbiology Letters. 2015; (362): 1 – 6. doi: 10.1093/femsle/fnv163.
9. Mahler GJ. Metabolic Engineering: Enzyme control on a chip. Nature Nanotechnology. 2014; (9): 571 – 572. doi: 10.1038/nnano.2014.160. PMID: 25064395.
10. Mahler GJ, Frendl CM, Cao Q, and Butcher JB. Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells. Biotechnology and Bioengineering. 2014; 111(11): 2326–2337. doi: 10.1002/bit.25291. PMID: 24898772.
11. Esch MB, Mahler GJ, Stokol T, and Shuler ML. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab on a Chip. 2014; 14: 3081–3092. doi: 10.1039/c4lc00371c. PMID: 24970651.
12. Mahler GJ, Farrar EJ and Butcher JB. Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013; 33(1): 121-30. doi: 10.1161/ATVBAHA.112.300504. PMID: 23104848.
13. Mahler GJ, Esch MB, Tako E, Southard TL, Archer SD, Glahn RP, and Shuler, ML. Oral exposure to polystyrene nanoparticles affects iron absorption. Nature Nanotechnology. 2012; 7(4): 264-270. doi: 10.1038/nnano.2012.3. PMID: 22327877.
14. Mahler GJ, Esch MB, Glahn RP, and Shuler ML. Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnology and Bioengineering. 2009; 104(1): 193-205. doi: 10.1002/bit.22366. PMID: 19418562.
15. Mahler GJ, Shuler ML, and Glahn, RP. Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability. Journal of Nutritional Biochemistry. 2009; 20(7): 494-502. PMID: 18715773.
Education
- BS, University of Massachusetts at Amherst
- PhD, Cornell University
Research Interests
- Organ-on-a-chip technology
- Tissue engineering
- Nanotoxicology
Awards
- 2017 Provost's Award for Outstanding Graduate Director
- 2015 Lush Prize
- 2015 Dr. Nuala McGann Drescher Award
- 2008 The Hartwell Foundation Postdoctoral Fellowship
- 2007 The Austin Hooey Graduate Research Excellence Recognition Award