Research & Interests
Communication between cells and the environment is essential for development, homeostasis and repair of tissues. Our research in this area focuses on the interaction between epithelial cells and the extracellular matrix. Our primary goal is to define how members of the laminin family of matrix molecules and their receptors regulate the behavior of skin and lung cells in normal and diseased tissues.
One of our projects involves studying cell surface receptors of the integrin family and the mechanisms via which they determine not only the precise pattern of deposition and assembly of laminin matrix in the skin but also cell polarity and motility. Our analyses involve molecular genetics, dissection of signaling cascades and live cell imaging. The movie below depicts our model of the molecular mechanisms governing motility and is consistent with data we published in a series of papers over the last few years (Sehgal et al., 2006; Kligys et al., 2009; Hamill et al., 2009, 2011, 2013).
In a second project, we have uncovered novel functions for laminin matrix in the transduction of mechanosignals in the alveolar epithelial compartment of the lung. We are currently working on how laminin regulates alveolar epithelial cell differentiation and how genetic manipulation of signaling pathways in alveolar epithelial cells impacts normal and diseased lung cell function in vivo and in vitro. We have also recently identified a highly unusual organization of matrix adhesions in primary lung cells maintained on a micropatterned substrate. These data are published in Eisenberg et al., 2013 (see cover picture below).
- Hiroyasu S, Colburn, ZT, Jones JCR (2016) A hemidesmosomal protein regulates actin dynamics and traction forces in motile keratinocytes. FASEB J. 30(6), 2298-310 PMID: 26936359 PMCID: PMC4871795
- Morales LI, Rogel MR, Eisenberg JL, Hamill KJ, Soberanes S, Nigdelioglu R, Takugo MC, Radigan KA, Ridge KM, Misharin AV, Woychek A, Hopkinson S, Perlman H, Mutlu GM, Pardo A, Selman M, Jones JCR (2015) Lung specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis. Am J Resp Cell Mol Biol. 52, 503-512 PMID: 25188360 PMCID: PMC4491119
- Hamill KJ, Hiroyasu S, Colburn ZT, Ventrella RV3, Hopkinson SB, Skalli O4, Jones JC (2015) Alpha actinin-1 regulates cell-matrix adhesion organization in keratinocytes: consequences for skin cell motility J Invest Dermatol. 135(4), 1043-52 PMID: 25431851 PMCID: PMC4366307
- Kligys K, Wu Y, Hamill K, Hopkinson S, Budinger GRS, Jones JCR (2013) Laminin-332 and a3b1 integrin-supported migration of bronchial epithelial cells is modulated by fibronectin Am J Resp Cell Mol Biol. 49, 731-740
- Eisenberg JE, Beaumont KG, Takawira D, Hopkinson SB, Mrksich M, Budinger GRS, Jones JCR (2013) Plectin-containing, centrally-localized focal adhesions exert traction forces in primary lung epithelial cells. J Cell Sci. 126, 3746-3755 PMID: 23750011 PMCID: PMC3744029
- Hiroyasu S, Ozawa T, Kobayashi H, Ishii M, Aoyama Y, Kitajima Y, Hashimoto T, Jones JCR, Tsuruta D (2013) Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway Am J Pathol. 182, 828-840 PMID: 23337823 PMCID: PMC3590760
- Hamill KJ, Hopkinson SB, Skalli O, Jones JC (2013) Actinin-4 in keratinocytes regulates motility via an impact on lamellipodia stability and matrix adhesions FASEB J. 27(2), 546-56 PMID: 23085994 PMCID: PMC3545541
- Hamill KJ, Hopkinson SB, Hoover P, Todorović V, Green KJ, Jones JCR (2012) Fibronectin expression determines skin cell motile behavior J Invest Derm. 132, 448-457 PMID: 21956124 PMCID: PMC3252482