Scholars@Duke

• Recognition
• 

  In the News

  • MAY 4, 2020

    Scanning Electron Microscope Images: Coming to a Screen Near You

  • APR 17, 2020

    A Bee’s Knees and Toilet Paper’s Fibrous Jungles—in Super-High Resolution

  • APR 2, 2020

    Duke Leverages Cryo-Electron Microscope Facility in the Race for Coronavirus Vaccine

  • MAY 24, 2018

    Girls STEM Day @ Duke Fuels the STEM Pipeline
• Expertise
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  Subject Headings

  • Microscopy
  • Microscopy, Atomic Force
  • Microscopy, Electron
  • Microscopy, Electron, Scanning Transmission
• Research
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  Selected Grants

  • NNCI: North Carolina Research Triangle Nanotechnology Network (RTNN) awarded by North Carolina State University 2020 - 2025
  • Regulation of Cartilage Mechanobiology by Hydrostatic Pressure awarded by  National Science Foundation 2014 - 2016
  • Viscoelastic Properties of Normal and OA Chondrons awarded by National Institutes of Health 1998 - 2016
  • Mechanical and Osmotic Signaling in Chondrocytes awarded by National Institutes of Health 2001 - 2015
• Publications & Artistic Works
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  Selected Publications

  • Academic Articles

    • Gilchrist, Christopher L., Holly A. Leddy, Laurel Kaye, Natasha D. Case, Katheryn E. Rothenberg, Dianne Little, Wolfgang Liedtke, Brenton D. Hoffman, and Farshid Guilak. “TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension.” Proc Natl Acad Sci U S A 116, no. 6 (February 5, 2019): 1992–97. https://doi.org/10.1073/pnas.1811095116.
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    • Lee, W., H. Leddy, A. McNulty, F. Guilak, and W. Liedtke. “Inflammatory Cytokine Il-1α Up-Regulates Piezo1 and Hyper-Sensitizes Chondrocytes to Compression.” Biophysical Journal 110, no. 3 (February 16, 2016): 349a-349a.
    • Zelenski, Nicole A., Holly A. Leddy, Johannah Sanchez-Adams, Jinzi Zhang, Paolo Bonaldo, Wolfgang Liedtke, and Farshid Guilak. “Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.” Arthritis Rheumatol 67, no. 5 (May 2015): 1286–94. https://doi.org/10.1002/art.39034.
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    • McNulty, Amy L., Holly A. Leddy, Wolfgang Liedtke, and Farshid Guilak. “TRPV4 as a therapeutic target for joint diseases.” Naunyn Schmiedebergs Arch Pharmacol 388, no. 4 (April 2015): 437–50. https://doi.org/10.1007/s00210-014-1078-x.
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    • Lee, Whasil, Holly A. Leddy, Yong Chen, Suk Hee Lee, Nicole A. Zelenski, Amy L. McNulty, Jason Wu, et al. “Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.” Proc Natl Acad Sci U S A 111, no. 47 (November 25, 2014): E5114–22. https://doi.org/10.1073/pnas.1414298111.
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    • Sanchez-Adams, Johannah, Holly A. Leddy, Amy L. McNulty, Christopher J. O’Conor, and Farshid Guilak. “The mechanobiology of articular cartilage: bearing the burden of osteoarthritis.” Curr Rheumatol Rep 16, no. 10 (October 2014): 451. https://doi.org/10.1007/s11926-014-0451-6.
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    • Leddy, Holly A., Amy L. McNulty, Suk Hee Lee, Nicole E. Rothfusz, Bernd Gloss, Margaret L. Kirby, Mary R. Hutson, Daniel H. Cohn, Farshid Guilak, and Wolfgang Liedtke. “Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations.” Faseb J 28, no. 6 (June 2014): 2525–37. https://doi.org/10.1096/fj.13-245936.
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    • O’Conor, Christopher J., Holly A. Leddy, Halei C. Benefield, Wolfgang B. Liedtke, and Farshid Guilak. “TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading.” Proc Natl Acad Sci U S A 111, no. 4 (January 28, 2014): 1316–21. https://doi.org/10.1073/pnas.1319569111.
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    • Leddy, Holly A., Amy L. McNulty, Farshid Guilak, and Wolfgang Liedtke. “Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias.” Rare Dis 2, no. 1 (2014): e962971. https://doi.org/10.4161/2167549X.2014.962971.
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    • Widmyer, Margaret R., Gangadhar M. Utturkar, Holly A. Leddy, Jeremy L. Coleman, Charles E. Spritzer, Claude T. Moorman, Louis E. DeFrate, and Farshid Guilak. “High body mass index is associated with increased diurnal strains in the articular cartilage of the knee.” Arthritis Rheum 65, no. 10 (October 2013): 2615–22. https://doi.org/10.1002/art.38062.
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    • McNulty, Amy L., Nicole E. Rothfusz, Holly A. Leddy, and Farshid Guilak. “Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation.” J Orthop Res 31, no. 7 (July 2013): 1039–45. https://doi.org/10.1002/jor.22334.
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    • Coleman, Jeremy L., Margaret R. Widmyer, Holly A. Leddy, Gangadhar M. Utturkar, Charles E. Spritzer, Claude T. Moorman, Farshid Guilak, and Louis E. DeFrate. “Diurnal variations in articular cartilage thickness and strain in the human knee.” J Biomech 46, no. 3 (February 1, 2013): 541–47. https://doi.org/10.1016/j.jbiomech.2012.09.013.
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    • Davis, Bryce H., Yoshihisa Morimoto, Chris Sample, Kevin Olbrich, Holly A. Leddy, Farshid Guilak, and Doris A. Taylor. “Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.” Journal of Biomechanical Engineering 134, no. 10 (October 2012): 101005. https://doi.org/10.1115/1.4007455.
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    • Christensen, Susan E., Jeffrey M. Coles, Nicole A. Zelenski, Bridgette D. Furman, Holly A. Leddy, Stefan Zauscher, Paolo Bonaldo, and Farshid Guilak. “Altered trabecular bone structure and delayed cartilage degeneration in the knees of collagen VI null mice.” Plos One 7, no. 3 (January 2012): e33397. https://doi.org/10.1371/journal.pone.0033397.
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    • Finan, John D., Holly A. Leddy, and Farshid Guilak. “Osmotic stress alters chromatin condensation and nucleocytoplasmic transport.” Biochemical and Biophysical Research Communications 408, no. 2 (May 2011): 230–35. https://doi.org/10.1016/j.bbrc.2011.03.131.
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    • Guilak, Farshid, Holly A. Leddy, and Wolfgang Liedtke. “Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system?” Ann N Y Acad Sci 1192 (March 2010): 404–9. https://doi.org/10.1111/j.1749-6632.2010.05389.x.
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    • Phan, Mimi N., Holly A. Leddy, Bartholomew J. Votta, Sanjay Kumar, Dana S. Levy, David B. Lipshutz, Suk Hee Lee, Wolfgang Liedtke, and Farshid Guilak. “Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes.” Arthritis Rheum 60, no. 10 (October 2009): 3028–37. https://doi.org/10.1002/art.24799.
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    • Leddy, Holly A., Susan E. Christensen, and Farshid Guilak. “Microscale diffusion properties of the cartilage pericellular matrix measured using 3D scanning microphotolysis.” Journal of Biomechanical Engineering 130, no. 6 (December 2008): 061002. https://doi.org/10.1115/1.2979876.
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    • Leddy, Holly A., and Farshid Guilak. “Site-specific effects of compression on macromolecular diffusion in articular cartilage.” Biophysical Journal 95, no. 10 (November 2008): 4890–95. https://doi.org/10.1529/biophysj.108.137752.
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    • Choi, Jae Bong, Inchan Youn, Li Cao, Holly A. Leddy, Christopher L. Gilchrist, Lori A. Setton, and Farshid Guilak. “Zonal changes in the three-dimensional morphology of the chondron under compression: the relationship among cellular, pericellular, and extracellular deformation in articular cartilage.” Journal of Biomechanics 40, no. 12 (January 2007): 2596–2603. https://doi.org/10.1016/j.jbiomech.2007.01.009.
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    • Leddy, Holly A., Mansoor A. Haider, and Farshid Guilak. “Diffusional anisotropy in collagenous tissues: fluorescence imaging of continuous point photobleaching.” Biophysical Journal 91, no. 1 (July 2006): 311–16. https://doi.org/10.1529/biophysj.105.075283.
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    • Fetter, Nicole L., Holly A. Leddy, Farshid Guilak, and James A. Nunley. “Composition and transport properties of human ankle and knee cartilage.” J Orthop Res 24, no. 2 (February 2006): 211–19. https://doi.org/10.1002/jor.20029.
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    • Tognana, E., F. Chen, R. F. Padera, H. A. Leddy, S. E. Christensen, F. Guilak, G. Vunjak-Novakovic, and L. E. Freed. “Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro.” Osteoarthritis and Cartilage 13, no. 2 (February 2005): 129–38. https://doi.org/10.1016/j.joca.2004.10.015.
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    • Leddy, Holly A., Hani A. Awad, and Farshid Guilak. “Molecular diffusion in tissue-engineered cartilage constructs: effects of scaffold material, time, and culture conditions.” Journal of Biomedical Materials Research. Part B, Applied Biomaterials 70, no. 2 (August 2004): 397–406. https://doi.org/10.1002/jbm.b.30053.
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    • Awad, Hani A., M Quinn Wickham, Holly A. Leddy, Jeffrey M. Gimble, and Farshid Guilak. “Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds.” Biomaterials 25, no. 16 (July 2004): 3211–22. https://doi.org/10.1016/j.biomaterials.2003.10.045.
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    • Guilak, Farshid, Hani A. Awad, Beverley Fermor, Holly A. Leddy, and Jeffrey M. Gimble. “Adipose-derived adult stem cells for cartilage tissue engineering.” Biorheology 41, no. 3–4 (January 2004): 389–99.
    • Leddy, Holly A., and Farshid Guilak. “Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching.” Annals of Biomedical Engineering 31, no. 7 (July 2003): 753–60. https://doi.org/10.1114/1.1581879.
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    • Johnson, Amy S., Olaf Ellers, Jim Lemire, Melissa Minor, and Holly A. Leddy. “Sutural loosening and skeletal flexibility during growth: determination of drop-like shapes in sea urchins.” Proceedings. Biological Sciences 269, no. 1488 (February 2002): 215–20. https://doi.org/10.1098/rspb.2001.1881.
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    • Gronthos, S., D. M. Franklin, H. A. Leddy, P. G. Robey, R. W. Storms, and J. M. Gimble. “Surface protein characterization of human adipose tissue-derived stromal cells.” J Cell Physiol 189, no. 1 (October 2001): 54–63. https://doi.org/10.1002/jcp.1138.
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    • Leddy, H. A., and A. S. Johnson. “Walking versus breathing: mechanical differentiation of sea urchin podia corresponds to functional specialization.” The Biological Bulletin 198, no. 1 (February 2000): 88–93. https://doi.org/10.2307/1542806.
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