Manuela Martins-Green

• Martins-Green, M. (1988). Origin of the dorsal surface of the neural tube by progressive delamination of epidermal ectoderm and neuroepithelium: Implications for neurulation and neural tube defects. Development 103: 687-706.
  In this seminal paper as a graduate student, I proposed a novel way by which the neural tube develops and closes and the potential consequences for Spina bifida if the process goes astray. My model was highlighted in a 1990 comprehensive review of mechanisms of neurulation as one of two important new ideas breaking ground on this subject and has been included in Developmental Biology textbooks.
• Martins-Green, M., M.J. Bissell (1990). Localization of 9E3/CEF4 in avian tissues: Expression is absent in RSV-induced tumors but is stimulated by injury. J. Cell Biol. 110: 581-595. (photo on journal cover).
  In this paper we discovered that tumors that develop due to viral infection do not necessarily retain components of the virus that can be detected in diagnostic assays. This was at the time a very unconventional proposition. Furthermore, we showed for the first time that chemokines are involved in response to injury caused by the tumor and in normal response to injury, in particular in the development of microvessels.
• Martins-Green, M., N. Boudreau, M.J. Bissell (1994). Inflammation is responsible for the development of wound tumors in RSV-infected newly-hatched chicks. Cancer Res. 54:4334-4341.
  In this publication we showed that Rous-Sarcoma-Virus (RSV) -induced tumors were dependent on inflammation and proposed that during inflammation macrophages play a key role for viral-induced tumor development and that this type of inflammation is also instrumental in HIV setting up of Aids because both injury and macrophages are critical for development of this disease.
• Feugate, J.E., QJ Li, S. Lu, M. Martins-Green (2001). The CXC chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure in vivo. Journal of Cell Biology 156:161-172.
  This study showed for the first time that chemokines stimulate another process of wound healing (contraction of the wound) in addition to angiogenesis, in this manner making solid the contributions of these small cytokines to wound healing, something that was not known previously. We obtained a patent for these findings.
• Li, Q-J., SH Yang, Y. Maeda, FM Sladek, AD Sharrocks, M. Martins-Green (2003). Map kinase phosphorylation-dependent activation of Elk-1 leads to activation of the coactivator p300. EMBO Journal 22(2): 1-11.
  The work presented here made new and significant experimental and conceptual contributions to the field of transcription. We identified novel interactions between transcription factor and co-activator that could play a critical role in chromatin remodeling and gene activation. This mechanism may be important in regulation of expression of immediate early response genes, in particular those involved in stress responses.
• Li, QJ, M. Yao, W. Wong, V. Parpura, M. Martins-Green. (2004). The N- and C-terminal peptides of hIL8/CSCL8 are ligands for hCXCR1 and hCXCR2. FASEB, 10:10961/fj.02-1175fje. Three page summary published in. FASEBJ 18:776-778, 2004.
  In this paper we used the chemokine IL-8/CXCL8 and discovered that multifunctionality of chemokines is related to the function of peptides that represent not only the N-terminus but also the C-terminus of these highly conserved molecules and that their functions lead to different outcomes. Up to this time only the N-terminus of chemokines was thought to have functionality.
• Martins-Green, M., Q-J Li and Min Yao (2004). Engineering human skin in culture using primary adult cells. FASEB Dec 9, [Epub].
  Here we show a new generation of organ cultures that mimics human skin. This system can help answer fundamental biological and medical questions and can potentially be developed to help with impaired healing. These procedures will help with development of more complex tissue and organ cultures prepared with adult human primary cells for studies of disease, testing of drugs, and potential application as replacement organs. This type of construction is now one of the topics for the TR01 RFAs at NIH.
• Petreaca, M., M. Yao, C. Ware, and M. Martins-Green (2008). VEGF promotes macrophage apoptosis through stimulation of tumor necrosis factor superfamily member 14 (Tnfsf14/Light). [Winner of a Young Investigator Award in 2006]. Wound Repair and Regeneration, 16:602-614.
  In this work we challenged the established paradigm that VEGF is a survival factor by demonstrating that it stimulates macrophage death during inflammation in vivo. We have gone on to delineate the process by which this occurs and proposed that during wound healing VEGF functions in resolution of inflammation through LIGHT.
• Yuan, H., M. Yao, and M. Martins-Green. (2006). Building of a 3-D Blood Vessel Culture System for Cardiovascular Research. Abstract for 5th California Tissue Engineering Meeting. University of California, Davis. Sept 15-16. Poster award for innovation.
• Q. Dai, H. Yuan, M. Yao, N. Zou, and M. Martins-Green (2009). A 3-D Multi-Cellular Human Arterial Wall Culture System for the Study of Blood Vessel Biology and Disease. Submitted.
  The work in both this publication and the one above describes the development of an arterial wall for studies on the effects of second hand cigarette smoke toxins on initiation of atherosclerotic plaque development. We show that indeed this system will be useful to study initiation of plaque formation. When monocytes are put in contact with this culture system they penetrate the wall of the vessel much more efficiently, and become macrophages, when in the presence of cigarette smoke. When exposed to smoke and oxidized LDL a "plaque" forms which contains macrophages which are full of lipid.