Piezo1, ion channels, stem cells, neural stem cells, differentiation, development, mechanical forces, matrix, environment
Howard Hughes Medical Institution's Gilliam Fellowship for Advanced Study
NIH Director's New Innovator Award
UCI Chancellor’s Award for Excellence in Undergraduate Research
UCI ADVANCE Faculty Career Development Award
Junior Faculty Fellow, Journal of General Physiology
GSK Neuroscience Discovery Award, FASEB Ion Channel Regulation Conference
Helen Hay Whitney Postdoctoral Fellowship
The long-term goal of my lab is to understand at molecular, cellular and organismal levels, how mechanical forces modulate neural stem cell fate in development and repair. We previously showed that the stretch-activated ion channel Piezo1 mediates mechanosensitive lineage specification of neural stem cells. Our studies revealed that Piezo1 activity in neural stem cells is modulated by matrix mechanics, and that it influences differentiation of the cells into neurons or astrocytes. Current work focuses on understanding (i) how Piezo1 detects and transduces matrix mechanical signals, (ii) how Piezo1 activity elicits gene expression changes, (iii) how Piezo1 may shape neural development, and (iv) how Piezo1 may be involved in certain disease states. We use a multi-disciplinary approach, combining ideas and techniques from ion channel biophysics, cell biology, optical imaging, stem cell biology and bioengineering.
* Denotes Equal Contribution
† Corresponding authors
Holt, J. R., Zeng, W.-Z., Evans, E. L., Woo, S.-H., Ma, S., Abuwarda, H., Loud, M., Patapoutian, A.†, Pathak, M. M.† (2021). Spatiotemporal dynamics Of PIEZO1 Localization Controls Keratinocyte migration during wound healing. eLife 2021;10:e65415.
Atcha, H., Meli, V. S., Davis, C. T., Brumm, K. T., Anis, S., Chin, J., & Jiang, K., Pathak M. M., Liu W. F. (2021). Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues. Frontiers in immunology, 12.
Atcha, H., Jairaman, A., Evans, E. L., Pathak, M. M., Cahalan, M. D., & Liu, W. F. (2021). Ion channel mediated mechanotransduction in immune cells. Current Opinion in Solid State and Materials Science, 25(6), 100951.
Jairaman A*, Othy S*, Dynes JL, Yeromin AV, Zavala A, Greenberg ML, Nourse JL, Holt JR, Cahalan SM, Parker I, Pathak MM, and Cahalan MD (2021). Piezo1 channels restrain regulatory T cell polarization but are dispensable for effector CD4+ T cell responses. Science Advances, 7(28).
Atcha H, Jairaman A, Holt JR, Meli VS, Nagalla RR, Veerasubramanian PK, Brumm KT, Lim HE, Cahalan MD, Pathak MM, and Liu WF (2021). Mechanically-activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nature Communications, 12(1), 1-14.
Abuwarda H, Pathak MM. (2020).
Mechanobiology of neural development.
Current Opinion in Cell Biology. 66:104-111.
Ellefsen K*, Chang A*, Holt JR*, Nourse JL*, Arulmoli A, Mekhdjian A, Abuwarda H, Tombola F, Flanagan LA, Dunn AR, Parker I, Pathak MM. (2019).
Myosin-II mediated traction forces evoke localized Piezo1 Ca2+ flickers.
Communications Biology. 2: 298.
Zhao C, Sun Q, Tang L, Cao Y, Nourse JL, Pathak MM, Lu X, Yang Q. (2019).
Mechanosensitive Ion Channel Piezo1 Regulates Diet-Induced Adipose Inflammation and Systemic Insulin Resistance.
Front Endocrinol (Lausanne). 10:373.
Nourse JL, Pathak MM (2017).
How cells channels their stress: Interplay betwen Piezo1 and the Cyoskeleton
Seminars in Cell and Development Biology. 2017 Nov; 71:3-12.
Pathak MM, Tran T, Hong L, Joós B, Morris CE, Tombola F (2016).
The Hv1 proton channel responds to mechanical stimuli.
Journal of General Physiology. 2016 Nov;148(5):405-418.
Arulmoli J, Wright HJ, Phan DTT, Sheth U, Que RA, Botten GA, Keating M, Botvinick EL, Pathak MM, Zarembinski TI, Yanni DS, Razorenova OV, Hughes CCW, Flanagan LA (2016).
Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell and vascular tissue engineering.
Acta Biomaterialia 2016 Oct 1;43:122-38.
Phan L*, Kautz R*, Arulmoli J, Kim I, Le DT, Shenk MA, Pathak MM†, Flanagan LA†, Tombola F†, Gorodetsky AA† (2016).
Reflectin as a Material for Neural Stem Cell Growth.
ACS Applied Materials & Interfaces. 13;8(1):278-84
† Corresponding authors.
Arulmoli J, Pathak MM, McDonnell LP, Nourse JL, Tombola F, Earthman JC, Flanagan LA. (2015)
Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner.
Scientific Reports. 5: 8499.
Pathak MM†, Nourse JL, Tran T, Hwe J, Arulmoli J, Le DTT, Bernardis E, Flanagan LA, Tombola F†. (2014)
Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells.
Proceedings of the National Academy of Sciences. 111(45):16148-53.
Kim IH, Hevezi P, Varga C, Pathak MM, Hong L, Ta D, Tran CT, Zlotnik A, Soltesz I, Tombola F. (2014).
Evidence for functional diversity between the voltage-gated proton channel Hv1 and its closest related protein HVRP1.
PLoS One. 9(8):e105926.
Nourse JL*, Prieto JL*, Dickson AR, Lu J, Pathak MM, Tombola F, Demetriou M, Lee AP, Flanagan LA. (2014).
Membrane biophysics define neuron and astrocyte progenitors in the neural lineage.
Stem Cells. 32(3):706-16.
Hong L, Pathak MM, Kim IH, Ta D, Tombola F. (2013).
Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.
Commentary: Kalia & Schwartz (2013). Common principles of voltage-dependent gating for Hv and Kv channels. Neuron. 77(2):214-6.
Pathak MM*, Yarov-Yarovoy V*, Roux B, Agarwal G, Kohout S, Barth P, Tombola F, Isacoff EY. (2007).
Closing in on the resting state of the Shaker K+ channel.
Tombola F, Pathak MM, Gorostiza P, Isacoff EY. (2007).
The twisted ion-permeation pathway of a resting voltage-sensing domain.
Tombola F, Pathak MM, Isacoff EY. (2006).
How does voltage open an ion channel?
Annual Review of Cell and Developmental Biology. 22:23-52.
Tombola F, Pathak MM, Isacoff EY. (2005).
How far will you go to sense voltage?
Tombola F, Pathak MM, Isacoff EY. (2005).
Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores.
Pathak MM, Kurtz L, Tombola F, Isacoff EY. (2005).
The cooperative voltage sensor motion that gates a potassium channel.
Journal of General Physiology.125:57-69.
NIH New Investigator Award (DP2AT01037, Principal Investigator).
Building the brain: How mechanical forces shape human neural development. $1,500,000. 9/30/2018 – 6/30/2023.
NIH R01 grant (R01NS109810, Principal Investigator).
Piezo1 in neural stem cell mechano-regulation. $1,117,990. 9/30/2018 – 6/30/2023.
HHMI Gilliam Fellowship for PI Advanced Studies (GT11549, Principal Investigator). Functional dynamics of Piezo1 and Traction Forces in Tissue Repair. $150,000. 9/1/2019 – 8/30/2022.
Center for Advanced Design & Manufacturing of Integrated Microfluidics (CADMIM) (Multi-PIs, Hui, Eddington, Pathak). Low-Shear Organoid Vortex Array (LOVA). $65,000. 3/1/2021 – 2/28/2022.
UCI NIH NIAMS P30 Skin Biology Resource-based Center Seed Grant (Multi-PIs, Pathak, Lowengrub). Piezo1 dynamics in keratinocyte migration during skin wound healing. $35,000. 1/1/2021 – 12/31/2021.
NIH Administrative Supplement to DP2 (Principal Investigator). $250,000. 9/1/2020 – 8/31/2021.
NIH Administrative Supplement to DP2 (Principal Investigator). $100,000. 9/1/2020 – 6/30/2023.
NIH Administrative Supplement to R01 (Principal Investigator). $250,000. 7/1/2020 – 6/30/2021.
NIH Diversity Supplement to R01 (Principal Investigator). $79,399. 4/1/2020 – 6/30/2022.
NIH R01 grant (Co-Investigator, Liu PI). Biophysical regulation of macrophage function. $2,062,810. 9/1/2020 – 8/31/2025.
NIH R21 grant (Co-Investigator, Liu PI). Regulation of Microglia by Tissue Stiffness and Piezo1 in Alzheimer’s Disease. $275,000. 9/30/2020 – 8/31/2022.
NIH R21 grant (Co-Investigator, Liu PI). Mechanical regulation of skin repair and regeneration. $275,000. 7/1/2020 – 6/30/2022.
American Society for Cell Biology
International Society for Stem Cell Research
Biomedical Engineering Society
American Association for the Advancement of Science
Cellular and Molecular Biosciences
Interdepartmental Neuroscience Program
Mathematical and Computational Biology
Medical Scientist Training Program
Sue and Bill Gross Stem Cell Research Center
Center for Complex Biological Systems