Russell Lab
The lab's goal is to understand cardiac remodeling in health and disease, which is almost certain to involve mechano-signaling and may provide a path for novel therapeutic targets to avoid heart failure over time.
Fundamental mechanobiology questions are how changes in load and strain link mechanosignaling pathways to actin assembly on heart muscle cells. We deliver local forces to heart cells in three dimensions and determine cellular changes using state-of-art biophysical, imaging, cell/molecular biology and proteomics. Techniques are refined on neonatal rat ventricular myocytes prior to use on myocytes derived from human induced pluripotent stem cells (hIPSC-CMs), and from human and adult rabbit hearts. Our approach is to relate micromechanical signaling to cell hypertrophy by growing cells in microenvironments of different compliance (stiffness) to mimic chronic load (disease), or by loading with micromagnets to mimic acute changes. We focus on actin and the actin capping protein, CapZ, to study sarcomere assembly. The specific hypothesis currently being tested is that actin assembly depends on CapZ modification by mechano-transduction signaling pathways, such as deacetylation via HDACs, phosphorylation by PKCe, and binding to phosphatidylinositol 4,5-bisphosphate (PIP2).
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Publications by date
- Dittloff KT, Iezzi A, Zhong JX, Mohindra P, Desai TA, Russell B. Transthyretin amyloid fibrils alter primary fibroblast structure, function and inflammatory gene expression. Am J Physiol Heart Circ Physiol. 2021 May 21. doi: 10.1152/ajpheart.00073.2021. Epub ahead of print. PMID: 34018852
- Russell B, Solís C. Mechanosignaling pathways alter muscle structure and function by post-translational modification of existing sarcomeric proteins to optimize energy usage. J Muscle Res Cell Motil. 2021 Feb 17. doi: 10.1007/s10974-021-09596-9. Epub ahead of print. PMID: 33595762
- Le LV, Mkrtschjan MA, Russell B, Desai TA. Hang on tight: reprogramming the cell with microstructural cues.Biomed Microdevices. 2019 Apr 6;21(2):43. [Full text in PDF]
- Solís C, Russell B. CapZ integrates several signaling pathways in response to mechanical stiffness. J Gen Physiol. 2019 Feb 26. [Full text in PDF]
- Mkrtschjan MA, Solís C, Wondmagegn AY, Majithia J, Russell B. PKC epsilon signaling effect on actin assembly is diminished in cardiomyocytes when challenged to additional work in a stiff microenvironment. Cytoskeleton. 2018 Jul 75(8): 363-371. [Full text in PDF]
- Le LV, Mohindra P, Fang Q, Sievers RE, Mkrtschjan MA, Solís C, Safranek CW, Russell B, Lee RJ, Desai TA. Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction. Biomaterials. 2018 Jul;169:11-21. [Full text in PDF]
- Mkrtschjan MA, Gaikwad SB, Kappenman KJ, Solís C, Dommaraju S, Le L, Desai TA, Russell B. Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography. J Cell Physiol. 2018 Apr; 233(4):3672-3683. [Full text in PDF]
- Ryba DM, Li J, Cowan CL, Russell B, Wolska BM, Solaro RJ. Long-Term Biased β-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy. Circulation. 2017 Mar 14;135(11):1056-1070. [Full text in PDF]
- Li J, Mkrtschjan MA, Lin YH, Russell B. Variation in stiffness regulates cardiac myocyte hypertrophy via signaling pathways. Canadian Journal of Physiology and Pharmacology. 2016 Jun 15:1-9. [Full text in PDF]
- Lin YH, Warren CM, Li J, McKinsey TA, Russell B. Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ. Cell Signal. 2016 May 13;28(8):1015-1024. doi: 10.1016/j.cellsig.2016.05.011. [Full text in PDF]
- Broughton KM, Li J, Sarmah E, Warren CM, Lin YH, Henze MP, Sanchez-Freire V, Solaro RJ, Russell B. A Myosin Activator improves Actin Assembly and Sarcomere Function of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes with a Troponin T Point Mutation. Am J Physiol Heart Circ Physiol. 2016 May 6:ajpheart.00162.2016. doi: 10.1152/ajpheart.00162.2016. [Full text in PDF]
- Lin YH, Swanson E, Li J, Mkrtschjan MA, Russell B. Cyclic mechanical strain of myocytes modifies CapZβ1 post translationally via PKCε. Journal of Muscle Research and Cell Motility 2015 Oct 1. [Full text in PDF] [Cover photo]
- Broughton KM, Russell B. Cardiomyocyte subdomain contractility arising from microenvironmental stiffness and topography. Biomech Model Mechanobiol. 2014 Oct 2.
- Li J, Tanhehco EJ, Russell B. Actin dynamics is rapidly regulated by the PTEN and PIP2 signaling pathways leading to myocyte hypertrophy. Am J Physiol Heart Circ Physiol. 2014 Sep 26. pii: ajpheart.00393.2014.
- Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Jun 8.
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Publications by date
- Li J, Russell B. Phosphatidylinositol 4,5-bisphosphate regulates CapZβ1 and actin dynamics in response to mechanical strain. Am J Physiol Heart Circ Physiol. 2013 Dec 1;305(11):H1614-23
- Allen M. Samarel, Yevgeniya Koshman, Erik R. Swanson, and Brenda Russell. Biophysical Forces Modulate the Costamere and Z-Disc for Sarcomere Remodeling in Heart Failure. Biological and Medical Physics, Biomedical Engineering 2013, pp 141-174
- Lin YH, Li J, Swanson ER, Russell B. CapZ and actin capping dynamics increase in myocytes after a bout of exercise and abates in hours after stimulation ends. J Appl Physiol. 2013 Jun;114(11):1603-9.
- Doroudian G, Curtis MW, Gang A, Russell B. Cyclic strain dominates over microtopography in regulating cytoskeletal and focal adhesion remodeling of human mesenchymal stem cells. Biochem Biophys Res Commun. 2012 Dec 17.
- Chu M, Koshman Y, Iyengar R, Kim T, Russell B, Samarel AM. Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NOi Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway. Journal of Signal Transduction Volume 2012, Article ID 473410, 11 pages
- Köllmer M, Keskar V, Hauk TG, Collins JM, Russell B, Gemeinhart RA. Stem Cell-Derived Extracellular Matrix Enables Survival and Multilineage Differentiation within Superporous Hydrogels. Biomacromolecules. 2012 Mar 22.
- Curtis MW, Budyn E, Desai TA, Samarel AM, Russell B. Microdomain heterogeneity in 3D affects the mechanics of neonatal cardiac myocyte contraction. Biomech Model Mechanobiol. 2012 Mar 11.
- Chu M, Iyengar R, Koshman YE, Kim T, Russell B, Martin JL, Heroux AL, Robia SL, Samarel AM. Serine-910 phosphorylation of focal adhesion kinase is critical for sarcomere reorganization in cardiomyocyte hypertrophy. Cardiovasc Res. 2011 Dec 1;92(3):409-19. Epub 2011 Sep 21.
- Curtis MW and B Russell. Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling. Pflugers Archiv – European Journal of Physiology. 2011. Jul; 462(1): 105-17.
- Andrews JL, Zhang X, McCarthy JJ, McDearmon EL, Hornberger TA, Russell B, Campbell KS, Arbogast S, Reid MB, Walker JR, Hogenesch JB, Takahashi JS and KA Essser. CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function. PNAS. Oct 2010.
- Collins JM, Goldspink PH and B Russell. Migration and proliferation of human mesenchymal stem cells is stimulated by different regions of the mechano-growth factor prohormone. J Mol Cell Cardiology. Sep 2010.
- Curtis MW, Sharma S, Desai TA and B Russell. Hypertrophy, gene expression, and beating of neonatal cardiac myocytes are affected by microdomain heterogeneity in 3D. Biomed. Microdev. 2010.
- Russell B, Curtis MW, Koshman YE and AM Samarel. Mechanical stress-induced sarcomere assembly for cardiac muscle growth in length and width. J Mol Cell Cardiol. 2010.
- Koshman YE, Piano MR, Russell B and DW Schwertz. Signaling responses after exposure to 5{alpha}-dihydrotestosterone or 17{beta}-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes. J Appl Physiol. 2010.
- Collins JM, Ayala P, Desai TA and B Russell. Three-dimensional culture with stiff microstructures increases proliferation and slows osteogenic differentiation of human mesenchymal stem cells. Small. 2009. [Cover picture in PDF]
- Biehl JK, Yamanaka S, Desai TA, Boheler KR and B Russell. Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography. Dev Dyn. 2009. Aug; 238(8): 1964-73. [Featured article summary in PDF]
- Hartman TJ, Martin JL, Solaro RJ, Samarel AM and B Russell. CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2 and PKC-dependent mechanisms. AJP: Cell. 2009. May; 296(5): C1034-9.
- Boateng SY, Senyo SE, Qi L, Goldspink PH and B Russell. Myocyte remodelling in response to hypertrophic stimuli requires nucleocytoplasmic shuttling of muscle LIM protein. J Mol Cell Cardiol. 2009. doi: 10.1016/j.yjmcc.2009.04.006.
- Biehl JK and B Russell. Introduction to stem cell therapy. J. Cardiovascular Nursing. 2009. Mar-Apr; 24(2): 98-103.
- Collins JM and B Russell. Stem cell therapy for cardiac repair. J. Cardiovascular Nursing. 2009. Mar-Apr; 24(2): 93-7.
- Curtis MW and B Russell. Cardiac tissue engineering. J. Cardiovascular Nursing. 2009. Mar-Apr; 24(2): 87-92.
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Publications by date
- Russell B and JM Collins. Hearty slices to plan for future health. Cardiovascular Research. 2008. doi: 10.1093/cvr/cvn347.
- Koshman YE, Waters SB, Walker LA, Los T, de Tombe P, Goldspink PH and B Russell. Delivery and visualization of proteins conjugated to quantum dots in cardiac myocytes. J Mol Cell Cardiol. 2008. doi: 10.1016/j.yjmcc.2008.08.006.
- Boateng SY and PH Goldspink. Assembly and maintenance of the sarcomere night and day. Cardiovasc Res. 2007 Oct 25.
- Norman JJ, Collins JM, Sharma S, Russell B and TA Desai. Microstructures in 3D biological gels affect cell proliferation. Tissue Engineering. 2007.
- Senyo SE, Koshman YE and B Russell. Stimulus interval, rate and direction differentially regulate phosphorylation for mechanotransduction in neonatal cardiac myocytes. FEBS Letters. 2007.
- Boateng SY, Belin RJ, Geenen DL, Margulies KB, Martin JL, Hoshijima M, de Tombe PP and B Russell. Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein. Am J Physiol Heart Circ Physiol. 2007 Jan; 292 (1):H259-69.
- Yu J and B Russell. Cardiomyocyte remodeling and sarcomere addition after uniaxial static strain in vitro. Journal of Histochemistry and Cytochemistry. 53: 1-6, 2005.
- Lateef SS, Boateng S, Ahluwalia N, Hartman TJ, Russell B and L Hanley. Three-dimensional chemical structures by protein functionalized micron sized beads bound to polylysine coated silicone surfaces. J Biomed Mater Res A. 2005 Mar 15;72A(4): 373-80.
- Boateng SY, Lateef SS, Mosley W, Hartman TJ, Hanley L and B Russell. RGD and YIGSR synthetic peptides facilitate identical cellular adhesion as laminin and fibronectin but alter the physiology of neonatal cardiac myocytes. Am J Physiol-Cell Physiology. 288:C30?8, 2005.
- Vracar-Grabar M and B Russell. Creatine Kinase is an Alpha Myosin Heavy Chain 3’UTR mRNA Binding Protein. Journal of Muscle Research and Cell Motility. 25:397-404. 2004.
- Mansour H, de Tombe PP, Samarel AM and B Russell. Restoration of resting sarcomere length after uniaxial static strain is regulated by PKC and FAK. Circ Research, 94: 642-649, 2004.
- Motlagh D, Hartman TJ, Desai TA and B Russell. Microfabricated grooves recapitulate neonatal myocyte connexin43 and N-cadherin expression and localization. J Biomed Mater Res. 67A148-57. 2003.
- Boateng SY, Hartman TJ, Ahluwalia N, Vidula H, Desai TA and B Russell. Inhibition of Fibroblast Proliferation in Cardiac Myocyte Cultures by Surface Microtopography. Am J. Physiol: Cell. 285:C171-C182, 2003.
- Motlagh D, Senyo SE, Desai TA and B Russell. Microtextured substrata alter gene expression, protein localization and the shape of cardiac myocytes. Biomaterials. 24: 2436-2476, 2003.
- Lateef S, Boateng S, Hartman TJ, Crot C, Russell B and L Hanley. Stretching and Fibroblast Growth on GRGDSP-Peptide Modified Silicone Membranes. Polymeric Materials Science & Engineering, 85, 403-404, 2002.
- Boateng S, Lateef SS, Crot CA, Motlagh D, Desai TA, Samarel AM, Russell B and L Hanley. Peptides bound to silicone membranes and 3D microfabrication for cardiac cell culture. Adv. Materials. 14: 461- 463, 2002.
- Motlagh D, Alden KJ, Russell B and J GarcÃa. Sodium current modulation by a tubulin/GTP coupled process in neonatal cardiac myocytes. J Physiol, 540.1, 93-103, 2002.
- Lateef S, Boateng S, Hartman TJ, Crot C, Russell B and L Hanley L Stretching and Fibroblast Growth on GRGDSP-Peptide Modified Silicone Membranes. Polymeric Materials: Science & Engineering 85, 403-404, 2001.
- Heidkamp MC and B Russell. Calcium not strain regulates localization of alpha-myosin heavy chain mRNA in oriented cardiac myocytes. Cell Tissue Research, 305:1221-127, 2001.
- Nikcevic G, Perhonen M, Boateng SY and B Russell. Translation is regulated via the 3′ untranslated region of alpha-myosin heavy chain mRNA by calcium but not by its localization. J. Muscle Research and Cell Motility. 21: 599-607, 2000.
- Ashley WW Jr and B Russell. Tenotomy decreases reporter protein synthesis via the 3′ untranslated region of the a-myosin heavy chain mRNA. Am J Physiol:Cell: 279: C257-C265, 2000.
- Deutsch J, Motlagh D, Russell B and TA Desai. Fabrication of Microtextured Membranes for Cardiac Myocyte Attachment and Orientation, J Biomed Mater Res.Applied Biomaterials, 53: 267-275, 2000.
- Desai TA, Deutsch J, Motlagh D and B Russell. Microfabricated in-vitro cell culture systems for investigating cellular interactions: fabricating a model system for cardiac myocytes. Proc. SPIE Vol. 3912, p 122-129, Micro- and Nanotechnology for Biomedical and Environmental Applications, Raymond P. Mariella, Ed., 2000.
- Russell B, Motlagh D and WW Ashley. Form follows function: How muscle shape is regulated by work. Journal of Applied Physiology. 88: 1127-1132, 2000.