Megan L. Rexius-Hall, PhD – Microphysiological Systems Engineering

About

I am a postdoctoral researcher in the Viterbi School of Engineering at the University of Southern California. I work in the Department of Biomedical Engineering in the Laboratory for Living Systems Engineering.

I earned my PhD in Bioengineering from the University of Illinois at Chicago and my BS in Biomedical Engineering from Boston University.

My areas of expertise are microphysiological systems/organs-on-chips, microfluidics, tissue engineering, microfabrication, computational fluid dynamics, cellular hypoxia, mechanobiology, cellular metabolism, exosomes, stem cell biology, vascular biology, and cardiac physiology.

Career Highlights

Select Grants

National Institutes of Health (NIH) K99/R00 Pathway to Independence Award. Read the press release from USC Viterbi.
American Heart Association (AHA) Postdoctoral Fellowship

Select Recent Publications

A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient, Science Advances (2022)

Abstract:

After a myocardial infarction, the boundary between the injured, hypoxic tissue and the adjacent viable, normoxic tissue, known as the border zone, is characterized by an oxygen gradient. Yet, the impact of an oxygen gradient on cardiac tissue function is poorly understood, largely due to limitations of existing experimental models. Here, we engineered a microphysiological system to controllably expose engineered cardiac tissue to an oxygen gradient that mimics the border zone and measured the effects of the gradient on electromechanical function and the transcriptome. The gradient delayed calcium release, reuptake, and propagation; decreased diastolic and peak systolic stress; and increased expression of inflammatory cascades that are hallmarks of myocardial infarction. These changes were distinct from those observed in tissues exposed to uniform normoxia or hypoxia, demonstrating distinct regulation of cardiac tissue phenotypes by an oxygen gradient. Our border-zone-on-a-chip model advances functional and mechanistic insight into oxygen-dependent cardiac tissue pathophysiology.

Citation:

Megan L. Rexius-Hall et al., A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient. Science Advances 8, eabn7097 (2022). https://doi.org/10.1126/sciadv.abn7097.

Mitochondrial division inhibitor 1 increases oxidative capacity and contractile stress generated by engineered skeletal muscle, The FASEB Journal (2020)

Abstract:

In skeletal muscle fibers, mitochondria are densely packed adjacent to myofibrils because adenosine triphosphate (ATP) is needed to fuel sarcomere shortening. However, despite this close physical and biochemical relationship, the effects of mitochondrial dynamics on skeletal muscle contractility are poorly understood. In this study, we analyzed the effects of Mitochondrial Division Inhibitor 1 (mdivi-1), an inhibitor of mitochondrial fission, on the structure and function of both mitochondria and myofibrils in skeletal muscle tissues engineered on micromolded gelatin hydrogels. Treatment with mdivi-1 did not alter myotube morphology, but did increase the mitochondrial turbidity and oxidative capacity, consistent with reduced mitochondrial fission. Mdivi-1 also significantly increased basal, twitch, and tetanus stresses, as measured using the Muscular Thin Film (MTF) assay. Finally, mdivi-1 increased sarcomere length, potentially due to mdivi-1-induced changes in mitochondrial volume and compression of myofibrils. Together, these results suggest that mdivi-1 increases contractile stress generation, which may be caused by an increase in maximal respiration and/or sarcomere length due to increased volume of individual mitochondria. These data reinforce that mitochondria have both biochemical and biomechanical roles in skeletal muscle and that mitochondrial dynamics can be manipulated to alter muscle contractility.

Citation:

Rexius-Hall, Megan L. et al. Mitochondrial division inhibitor 1 (mdivi-1) increases oxidative capacity and contractile stress generated by engineered skeletal muscle. FASEB Journal: official publication of the Federation of American Societies for Experimental Biology. 34 (9): 11562-11576, 2020. https://doi.org/10.1096/fj.201901039RR.