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Molecular and Biophysical mechanisms of 
Mechanotransduction

Mechanical forces are ubiquitous in biological systems. Yet, we understand little about how cells sense and respond to these stimuli. To address this challenged, we study how mechanosensitive ion channels and G protein coupled Receptors sense and respond to mechanical forces such as membrane stretch, applied force, and fluid shear stress. We use protein engineering, force-clamp electrophysiology, fluorescence imaging, and theoretical modeling to discover biophysical principles underlying these processes. We also create genetically-encoded fluorescent indicators for in vitro and in vivo real-time monitoring of mechanotransduction signaling and explore ultrasound-based approaches for safe and non-invasive delivery of therapeutic mechanical stimuli.

 
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Jerome Lacroix, PhD

Assistant Professor

Western University of Health Sciences

Education

PhD, Cell and Molecular Biology (2006)

University of Nice-Sophia Antipolis


Master of Science in Molecular Pharmacology (2002)

University of Nice-Sophia Antipolis


Bachelor of Science, Cell Biology, Genetics, and Physiology (2001)

École Normale Supérieure de Lyon

Claude-Bernard University Lyon

Contact
 

Lab members

 
 

Our Electrophysiology and imaging systems

 
 

Publications

2004

Lacroix J, Poët M, Maehrel C, Counillon L. A mechanism for the activation of the Na/H exchanger NHE-1 by cytoplasmic acidification and mitogens. EMBO Rep. 2004 Jan;5(1):91-6. doi: 10.1038/sj.embor.7400035. PubMed PMID: 14710192; PubMed Central PMCID: PMC1298952.

2008

Tekpli X, Huc L, Lacroix J, Rissel M, Poët M, Noël J, Dimanche-Boitrel MT, Counillon L, Lagadic-Gossmann D. Regulation of Na+/H+ exchanger 1 allosteric balance by its localization in cholesterol- and caveolin-rich membrane microdomains. J Cell Physiol. 2008 Jul;216(1):207-20. doi: 10.1002/jcp.21395. PubMed PMID: 18264982.

Lacroix J, Poët M, Huc L, Morello V, Djerbi N, Ragno M, Rissel M, Tekpli X, Gounon P, Lagadic-Gossmann D, Counillon L. Kinetic analysis of the regulation of the Na+/H+ exchanger NHE-1 by osmotic shocks. Biochemistry. 2008 Dec 23;47(51):13674-85. doi: 10.1021/bi801368n. PubMed PMID: 19035652.

2011

Lacroix JJ, Labro AJ, Bezanilla F. Properties of deactivation gating currents in Shaker channels. Biophys J. 2011 Mar 2;100(5):L28-30. doi: 10.1016/j.bpj.2011.01.043. PubMed PMID: 21354387; PubMed Central PMCID: PMC3043211.

Lacroix JJ, Bezanilla F. Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6444-9. doi: 10.1073/pnas.1103397108. Epub 2011 Apr 4. PubMed PMID: 21464282; PubMed Central PMCID: PMC3081032.

Lacroix J, Halaszovich CR, Schreiber DN, Leitner MG, Bezanilla F, Oliver D, Villalba-Galea CA. Controlling the activity of a phosphatase and tensin homolog (PTEN) by membrane potential. J Biol Chem. 2011 May 20;286(20):17945-53. doi: 10.1074/jbc.M110.201749. Epub 2011 Mar 17. PubMed PMID: 21454672; PubMed Central PMCID: PMC3093869.

2012

Allen MJ, Lacroix JJ, Ramachandran S, Capone R, Whitlock JL, Ghadge GD, Arnsdorf MF, Roos RP, Lal R. Mutant SOD1 forms ion channel: implications for ALS pathophysiology. Neurobiol Dis. 2012 Mar;45(3):831-8. doi: 10.1016/j.nbd.2011.08.031. Epub 2011 Sep 10. PubMed PMID: 21930207; PubMed Central PMCID: PMC3384721.

Pang V, Counillon L, Lagadic-Gossmann D, Poet M, Lacroix J, Sergent O, Khan R, Rauch C. On the role of the difference in surface tensions involved in the allosteric regulation of NHE-1 induced by low to mild osmotic pressure, membrane tension and lipid asymmetry. Cell Biochem Biophys. 2012 May;63(1):47-57. doi: 10.1007/s12013-012-9340-7. PubMed PMID: 22331497; PubMed Central PMCID: PMC3326373.

Lacroix JJ, Bezanilla F. Tuning the voltage-sensor motion with a single residue. Biophys J. 2012 Aug 8;103(3):L23-5. doi: 10.1016/j.bpj.2012.06.030. PubMed PMID: 22947880; PubMed Central PMCID: PMC3414891.

Labro AJ, Lacroix JJ, Villalba-Galea CA, Snyders DJ, Bezanilla F. Molecular mechanism for depolarization-induced modulation of Kv channel closure. J Gen Physiol. 2012 Nov;140(5):481-93. doi: 10.1085/jgp.201210817. Epub 2012 Oct 15. PubMed PMID: 23071266; PubMed Central PMCID: PMC3483114.

Lacroix JJ, Pless SA, Maragliano L, Campos FV, Galpin JD, Ahern CA, Roux B, Bezanilla F. Intermediate state trapping of a voltage sensor. J Gen Physiol. 2012 Dec;140(6):635-52. doi: 10.1085/jgp.201210827. PubMed PMID: 23183699; PubMed Central PMCID: PMC3514728.

2013

Lacroix JJ, Campos FV, Frezza L, Bezanilla F. Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation. Neuron. 2013 Aug 21;79(4):651-7. doi: 10.1016/j.neuron.2013.05.036. PubMed PMID: 23972594; PubMed Central PMCID: PMC3907179.

Priest MF, Lacroix JJ, Villalba-Galea CA, Bezanilla F. S3-S4 linker length modulates the relaxed state of a voltage-gated potassium channel. Biophys J. 2013 Nov 19;105(10):2312-22. doi: 10.1016/j.bpj.2013.09.053. PubMed PMID: 24268143; PubMed Central PMCID: PMC3838747.

2014

Lacroix JJ, Hyde HC, Campos FV, Bezanilla F. Moving gating charges through the gating pore in a Kv channel voltage sensor. Proc Natl Acad Sci U S A. 2014 May 13;111(19):E1950-9. doi: 10.1073/pnas.1406161111. Epub 2014 Apr 29. PubMed PMID: 24782544; PubMed Central PMCID: PMC4024920.

Kubota T, Lacroix JJ, Bezanilla F, Correa AM. Probing α-3(10) transitions in a voltage-sensing S4 helix. Biophys J. 2014 Sep 2;107(5):1117-1128. doi: 10.1016/j.bpj.2014.07.042. PubMed PMID: 25185547; PubMed Central PMCID: PMC4156671.

2015

Labro AJ, Priest MF, Lacroix JJ, Snyders DJ, Bezanilla F. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization. Nat Commun. 2015 Dec 17;6:10173. doi: 10.1038/ncomms10173. PubMed PMID: 26673941; PubMed Central PMCID: PMC4703866.

2017

Botello-Smith WM, Alsamarah A, Chatterjee P, Xie C, Lacroix JJ, Hao J, Luo Y. Polymodal allosteric regulation of Type 1 Serine/Threonine Kinase Receptors via a conserved electrostatic lock. PLoS Comput Biol. 2017 Aug;13(8):e1005711. doi: 10.1371/journal.pcbi.1005711. eCollection 2017 Aug. PubMed PMID: 28827795; PubMed Central PMCID: PMC5578689.

Chatterjee P, Botello-Smith WM, Zhang H, Qian L, Alsamarah A, Kent D, Lacroix JJ, Baudry M, Luo Y. Can Relative Binding Free Energy Predict Selectivity of Reversible Covalent Inhibitors?. J Am Chem Soc. 2017 Dec 13;139(49):17945-17952. doi: 10.1021/jacs.7b08938. Epub 2017 Nov 29. PubMed PMID: 29124934; PubMed Central PMCID: PMC5729052.

2018

Brugarolas P, Sánchez-Rodríguez JE, Tsai HM, Basuli F, Cheng SH, Zhang X, Caprariello AV, Lacroix JJ, Freifelder R, Murali D, DeJesus O, Miller RH, Swenson RE, Chen CT, Herscovitch P, Reich DS, Bezanilla F, Popko B. Development of a PET radioligand for potassium channels to image CNS demyelination. Sci Rep. 2018 Jan 12;8(1):607. doi: 10.1038/s41598-017-18747-3. PubMed PMID: 29330383; PubMed Central PMCID: PMC5766510.

Lacroix JJ, Botello-Smith WM, Luo Y. Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1. Nat Commun. 2018 May 23;9(1):2029. doi: 10.1038/s41467-018-04405-3. PubMed PMID: 29795280; PubMed Central PMCID: PMC5966384.

2019

Lacroix JJ, Ozkan AD. Multiplexing Focused Ultrasound Stimulation with Fluorescence Microscopy. J Vis Exp. 2019 Jan 7;(143). doi: 10.3791/58781. PubMed PMID: 30663695; PubMed Central PMCID: PMC7098245.

Botello-Smith WM, Jiang W, Zhang H, Ozkan AD, Lin YC, Pham CN, Lacroix JJ, Luo Y. A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1. Nat Commun. 2019 Oct 3;10(1):4503. doi: 10.1038/s41467-019-12501-1. PubMed PMID: 31582801; PubMed Central PMCID: PMC6776524.

2020

Xie C, Jiang W, Lacroix JJ, Luo Y, Hao J. Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling. Int. J. Mol. Sci. 2020, 21(18), 6498; https://doi.org/10.3390/ijms21186498

 

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