E. Benjamin Randall, Ph.D.

With his background in mathematical modeling and analysis, Ben is working on multiple projects in the lab.

Cardiovascular physiology and its control mechanisms

Ben’s previous work focused modeling systemic cardiovascular physiology and its control neurological control mechanisms, including the baroreceptor reflex (baroreflex) and respiratory sinus arrhythmia. His work analyzed patient heart rate data to develop a model-based analysis of baroreflex heart rate control [1]. Armed with this expertise, Ben works with Filip in the development of a detailed representation of cardiovascular function that incorporates baroreflex control of heart rate, cardiac contractility, arteriolar resistance, and venous compliance. This model responds to various tests including the Valsalva maneuver, head-up tilt, and exercise. Moreover, Ben is currently working on developing a methodology for making this model (and simpler ones) species-specific, that is, this project has the benefit of using a suite of cardiovascular models for different species including humans, rats, and mice. Ben has also worked with Feng on his project analyzing the baroreflex’s influence in long-term blood pressure regulation [2].

[1] Randall, E.B., Billeschou, A., Brinth, L.S., Mehlsen, J., and Olufsen, M.S. A model-based analysis of autonomic nervous function in response to the Valsalva maneuver. J Appl Physiol 127: 1386–1402, 2019. doi: 10.1152/japplphysiol.00015.2019.

[2] Gu, Feng, Randall, E.B., Whitesall, S., Converso-Baran, K., Carlson, B.E., Fink, G.D., Michele, D.E., Beard, D.A. Intermittent functioning of baroreflex contributes to the etiology of hypertension in spontaneously hypertensive rats. Submitted.

 Induced pluripotent stem-cell derived cardiomyocytes (iPSC-CMs)

iPSC-CMs show promise as patient-specific surrogate for a donor’s individual cardiomyocytes, retaining disease markers and preserving cardiac phenotypes. However, these cells are immature, spontaneously beat, and exhibit structural differences. Furthermore, there is variability both within and between iPSC-CM labs. Since coming to UM, Ben works with Brian analyzing the efficacy of iPSC-CM mathematical models in determining patient-specific outcomes including time series analysis of action potential (AP) and calcium (CaT) data and discrete analysis of AP and CaT features. In particular, Ben has determined a subset of identifiable parameters of the gene expression O’Hara Rudy (GSORd) model, which can be used as both a model for human atrioventricular cardiomyocytes and iPSC-CMs. The GSORd model shows promise in linking cardiac performance between human heart tissue from an individual subject and the iPSC-CMs derived from that subject.

Models, simulation results and parameter sensitivity of hiPSC-CM electrophysiology and Ca2+ handling