From Cardiac Systems Biology Lab

Main: Research

Cardiac Regeneration. While cardiac regeneration was once thought to be limited to organisms such newts and zebrafish, recent studies have demonstrated that mammals also have some regenerative capacity. We are combining genomic and high-throughput microscopy experiments with computational models to map the molecular networks and identify compounds that stimulate cardiac myocyte proliferation.

  1. Woo L, Tkachenko S, Ding M, Plowright AT, Engkvist O, Andersson H, Drowley L, Barrett I, Firth M, Wolf MJ, Bekiranov S, Brautigan DL, Wang QD, *Saucerman JJ. High-content phenotypic screen for compounds that induce proliferation of human iPSC-derived cardiomyocytes. Circulation 2016;134:A18674. AHA Scientific Sessions Abstract (link).

Cardiac inflammation and extracellular matrix remodeling. Cardiac macrophages and fibroblasts play important roles in inflammation and wound healing following cardiac injury. Yet systems and therapeutic approaches targeting these cells have been limited. We are collaborating with investigators at UVA and externally to reconstruct the molecular networks in fibroblasts and macrophages in the context of myocardial infarction.

  1. *Lindsey ML, Saucerman JJ, DeLeon-Pennell K. Knowledge gaps to understanding cardiac macrophage polarization following myocardial infarction. Biochim Biophys Acta. 2016 May 27. pii: S0925-4439(16)30129-6. doi: 10.1016/j.bbadis.2016.05.013. [Epub ahead of print]
  2. Zeigler AC, Richardson WJ, Holmes JW, *Saucerman JJ. A computational model of cardiac fibroblast signaling predicts context-dependent drivers of myofibroblast differentiation. J Mol Cell Cardiol. 2016 May;94:72-81.
  3. Zeigler, AC, Richardson WJ, Holmes JW, *Saucerman JJ. Computational modeling of cardiac fibroblasts and fibrosis. J Mol Cell Cardiol. 2016 Apr;93:73-83.

Cardiac hypertrophy. Dozens of pathways are implicated in cardiac myocyte growth, but little is known about the quantitative contribution of these pathways to myocyte shape, reversibility, sarcomeric organization, or many other factors affecting the progression of heart failure. We are combining high-throughput microscopy, automated image processing, and large-scale network modeling to address these challenges.

  1. Ryall KA, *Saucerman JJ. Automated Microscopy of Cardiac Myocyte Hypertrophy: A Case Study on the Role of Intracellular α-Adrenergic Receptors. Methods Mol Biol. 2015; 1234:123-34.
  2. Ryall, K. A., V. J. Bezzerides, A. Rosenzwieg, Saucerman JJ. Phenotypic screen quantifying differential regulation of cardiac myocyte hypertrophy identifies CITED4 regulation of myocyte elongation. J Mol Cell Cardiol 2014 [Epub ahead of print], 10.1016/j.yjmcc.2014.02.013.

β-adrenergic signaling and beta blockers in heart failure. Do beta blockers work by suppressing or resensitizing the β-adrenergic pathway? Would patients with receptor polymorphisms benefit from personalized therapies? We are coupling integrated models of signaling and contractile function with video microscopy of Ca2+ dynamics.

  1. Amanfu RK, Saucerman JJ. Modeling the effects of beta1-adrenergic receptor blockers and polymorphisms on cardiac myocyte Ca2+ handling. Mol Pharmacol 2014 May 27. pii: mol.113.090951.

cAMP/PKA compartmentation. cAMP and PKA are central hubs transmitting signals from dozens of receptors to hundreds of effectors. We are studying how compartmentation (subcellular localization) of cAMP and PKA determines the input/output specificity of the network. Key methods are imaging genetically-encoded FRET biosensors and computational models with realistic cellular geometries. Dysregulated cAMP compartmentation is a key element of heart failure.

  1. Saucerman JJ, Greenwald EC, Polanowska-Grabowska R. Mechanisms of cyclic AMP compartmentation revealed by computational models. J Gen Physiol. 2014 Jan;143(1):39-48. PMCID: 3874575.
  2. Yang JH, Polanowska-Grabowska RK, Smith JS, Shields CW, Saucerman JJ. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic stimulation. J Mol Cell Cardiol, 2013 Nov 10;66C:83-93.[Epub ahead of print]. PMCID: 3927644.

Funding: National Institutes of Health, National Science Foundation, American Heart Association, AstraZeneca, Coulter Foundation, University of Virginia

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Page last modified on January 04, 2017, at 11:21 AM EST