My research program focuses on understanding the cell and molecular basis of wound healing.  Our work has three foci: (1) Normal healing. We study primarily the activation, expression, function and mode of action of chemokines in healing, using animal models and complex human cultures. Our studies have focused on the chemokine Interleukine-8 (IL-8), what agents at the wound site stimulate its expression, the signal-transduction mechanisms by which this expression occurs, and what functions IL-8 performs during the healing process. Our aim is to: (a) Identify commonalities in the signal transduction and transcription activation mechanisms that may lead the way to regulating the expression of chemokines for potential medical applications; (b) test the effects of IL-8 on the principal cellular components of the granulation tissue of wounds -- fibroblasts, myofibroblasts, endothelial cells, keratinocytes and immune cells – accompanied by tests directly to wounds; (c) characterize the function of IL-8 receptor(s) during wound healing. (2) Impaired healing.  Effects of environmental toxicants, especially those present in cigarette smoke.  We study the effects of second-hand smoke on: (a) the development of atherosclerosis (a form of impaired healing); (b) delay of skin and cornea wound healing. Our aim here is to identify key processes affected by cigarette smoke and which chemicals in the smoke cause those effects. (3) Engineering of human tissues.  In order to test the relevance for human biology of some of the hypotheses we have developed in animal systems, we are developing complex tissue cultures using primary human cells. We have already developed a novel human “skin” organ culture that we are now using to study some of the fundamental cell and molecular processes in normal and abnormal healing of skin.  We have also developed a system that allows us to test the effects of inflammatory agents on endothelial permeability and we are currently developing an arterial wall model and a lung epithelial/endothelial blood barrier system for studies of atherogenesis induced by first- and second-hand cigarette smoke.

Selected recent publications

Wong, L. and M. Martins-Green (2004).  “Firsthand” cigarette smoke alters fibroblasts migration and survival:  Implications for impaired Healing.  Wound Repair and Regeneration 12(4):471-84.

Martins-Green, M. Q-J Li and Min Yao (2004). A new generation organ culture arising from cross-talk between multiple primary human cell types. Epub 2004 Dec 9. PMID: 15591154.

Li, Qi-Jing, Min Yao, Melissa Dueck, Vladimir  Parpura  and Manuela Martins-Green (2005).  cCXCR1 is a Receptor for  cIL8 (9E3/cCAF) and its N- and C-Terminal Peptides, and is also Activated by hIL8 (CXCL8). J. Leukocyte Biology, 77:1-14.

Yao, Min, Rui-Hai Zhou, Melissa Petreaca, John Shyy and Manuela Martins-Green (2006). “Signal Transduction Pathways Stimulated by Different Types of Angiogenic Factors Converge in Activation of SREBPs and RhoA”.   J. Leukocyte Biology 80(3): 608-20. Epub 2006 Jul 18.

Dueck-Petreaca, Melissa and Martins-Green (2006). "Biologic and Molecular Basis of Regenerative Medicine: Cell-Extracellular Matrix Interactions" in Principles of Regenerative Medicine, edited by Anthony Atala, Robert Lanza, James Thomson, Robert Nerem.

Dueck-Petreaca, Melissa and Martins-Green (2006). "Cell-Extracellular Matrix Interactions with implications for Tissue engineering" in Principles of Tissue engineering, 3^rd edition, edited by Robert Lanza, Robert Langer and Joseph Vacanti.

Hongwei Yuan, Lina Wong, Monideepa Bhattacharya, Matthias Schneider, Robert E. Pitas and Manuela Martins-Green. Second-Hand Smoke Effects on Biological Processes Important in Atherogenesis.  BMC Cardiovascular Disease, in Press.