Project Description

The objective of this project is to study the biomechanics and mechanobiology of hyaluronan and its role in modulating the synthesis and bioactivity of the hyaluronan molecule. Hyaluronan is a deceptively simple polysaccharide molecule whose biological roles include inflammation, wound healing, and metastasis. These biological roles for hyaluronan also interact with its mechanical or physical functions, including structural support of various tissues and lubrication in the eye, synovial joint, and other organs.

Despite these diverse and important biological functions and the near ubiquitous presence of hyaluronan in almost all tissues of the body, understanding of how mechanical loading interacts with biological signaling to produce different molecular weights, concentrations, and configurations of hyaluronan at the cellular level is limited. Furthermore, how these biophysical and biological factors interact to alter the emergent properties at the tissue scale remains poorly understood. Importantly, it is unknown how biomechanical signaling to the cell alters the activity of the three different enzymes that may synthesize hyaluronan nor how the products of these enzymes alter mechanical properties of the tissue. This project therefore combines experimental and computational approaches at the cell and tissue scales to probe the effect of mechanical loading on hyaluronan metabolism and bioactivity.

Start Date

05/15/2022

Postdoctoral Qualifications

The ideal candidate will be able to demonstrate…
• A Ph.D. in Biomedical, Biomechanical, Mechanical Engineering, or closely related field
• Expertise in experimental or computational biomechanics or mechanobiology
• Familiarity with atomic force microcopy and/or nanoindentation or willingness to learn
• Ability to independently design, conduct, and document experiments
• Critical thinking, curiosity, and creativity in multidisciplinary research
• Effective project and time management, mentorship, leadership, and interpersonal skills
• Strong oral and written communication

The successful candidate will also be responsible for preparing manuscripts for publication, traveling to and presenting research results at scientific meetings, and working with the PI to manage research activities in the lab and train students. Postdocs are also expected to apply for external support and to develop additional independent projects in biomechanics and mechanobiology as part of their training to become independent investigators.

Co-Advisors

Deva Chan, Weldon School of Biomedical Engineering
Eric Nauman, School of Mechanical Engineering

Bibliography

• Chan DD, Xiao WF, Li J, de la Motte CA, Sandy JD, Plaas A. Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage. Osteoarthritis Cartilage. 2015;23(11):1879-89. Epub 2015/11/03. doi: 10.1016/j.joca.2015.06.021. PubMed PMID: 26521733; PMCID: PMC4630789.
• Sikes KJ, Renner K, Li J, Grande-Allen KJ, Connell JP, Cali V, Midura RJ, Sandy JD, Plaas A, Wang VM. Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa. J Orthop Res. 2018;36(10):2622-32. Epub 2018/04/20. doi: 10.1002/jor.24027. PubMed PMID: 29672913; PMCID: PMC6203660.
• Nagy N, de la Zerda A, Kaber G, Johnson PY, Hu KH, Kratochvil MJ, Yadava K, Zhao W, Cui Y, Navarro G, Annes JP, Wight TN, Heilshorn SC, Bollyky PL, Butte MJ. Hyaluronan content governs tissue stiffness in pancreatic islet inflammation. J Biol Chem. 2018;293(2):567-78. Epub 2017/12/01. doi: 10.1074/jbc.RA117.000148. PubMed PMID: 29183997; PMCID: PMC5767862.
• Voutouri C, Stylianopoulos T. Accumulation of mechanical forces in tumors is related to hyaluronan content and tissue stiffness. PLoS One. 2018;13(3):e0193801. Epub 2018/03/22. doi: 10.1371/journal.pone.0193801. PubMed PMID: 29561855; PMCID: PMC5862434.
• Hasib A, Hennayake CK, Bracy DP, Bugler-Lamb AR, Lantier L, Khan F, Ashford MLJ, McCrimmon RJ, Wasserman DH, Kang L. CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice. Am J Physiol Endocrinol Metab. 2019;317(6):E973-E83. Epub 2019/09/25. doi: 10.1152/ajpendo.00215.2019. PubMed PMID: 31550181; PMCID: PMC6957377.