Individual Listing

2117 BIOLOGICAL SCI
University of California
Riverside, CA 92521

Martins-Green, Manuela

Professor of Cell Biology

College of Natural and Agricultural Sciences

Cell Biology & Neuroscience


Biography

Field of Specialization: Cell and Molecular Biology of chemokines in Wound Healing and Tumorigenesis.

Degrees

M.S. Plant Pathology 1975

UC Riverside

Ph.D. Zoology 1987

UC Davis

Awards

NRSA Postdoctoral Fellowship (NIH), 1988-91
Associate Editor, Journal of Molecular Oncology, 1995-98
Department of Defense Breast Cancer Review Panel, Immunology Study Section #2, 1998-present
Faculty Development Award, UC Riverside, 1999-2000
Visiting Scientist, Molecular Immunoreg. Laboratory, National Cancer Institute, 2000
Nominee for Outstanding Teaching Award, UC Riverside, Spring 2000
Selected to organize a pre-meeting sub-group symposium on "The Cell Biology of Chemokines in Host Defense, Wound Healing & Disease" for annual ASCB Meeting, 2000
Invited participant as a chemokine expert on a workshop sponsored by Radiation Research Program, Division of Cancer Treatment and Diagnosis, NCI, September 2000
Proposal selected for presentation at ASCB entitled "The Cell Biology of Chemokines in Host Defense, Wound Healing & Disease" 2000
Member, American Society for Cell Biology Standing Committee, WICB 2001
Abstract selected for ASCB Press Book, 2001
Chair, Bioengineering Session at the Wound Healing Society Annual Meeting, 2002
Main speaker, Gordon Conference in Vascular Biology, 2003


Research Area

The work in my laboratory centers on studying the mechanisms of chemokine function in wound healing and tumor development. Chemokines are highly conserved proteins among higher vertebrates, are critical activators of the immune system, and are important not only in inflammatory diseases but also in healing, tumorigenesis and viral infections (e.g., HIV). Our work concentrates on two aspects of chemokine biology: (1) Determining the signal transduction and transcription activation mechanisms leading to expression of chemokines upon stimulation by stress-inducing agents associated with injury and tumorigenesis; (2) determining the functions of chemokines during wound healing and tumor development. To understand chemokine stimulation, we investigate (a) agents released upon injury, e.g. thrombin, (b) environmental toxicants, e.g. tobacco smoke, (c) radiation effects, e.g. ionizing radiation. In our work on chemokine function, we have determined that certain chemokines, such as IL-8 and its homologues, are angiogenic (stimulate formation of new blood vessels from pre-existing ones) and stimulate fibroblasts to differentiate into myofibroblasts, thereby accelerating wound contraction and closure. We have now developed a 3D co-culture system of primary human cells that mimics human skin in vivo, but in which we can control and manipulate the cells, to determine the molecular mechanisms by which human chemokines are stimulated and participate in angiogenesis, myofibroblast differentiation, and other aspects of tissue repair and tumorigenesis. Chemokines are very attractive targets for drug development because they are small inducible proteins that are easy to produce and modify, and they activate seven-transmembrane receptors that are highly amenable to pharmacological manipulations.

Publications

Li, QJ., S. Vaingankar, H. M. Green, M. Martins-Green (1999). Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge in MEK1/ERK2 and activate the Elk1 transcription factor. J. Biol. Chem. 274:15454-15465.

Martins-Green, M. (2000). The 9E3/cCAF chemokine. Chapter 10012 in A Compendium of Cytokines and Other Mediators of Host Defense, eds. J. Oppenheim, S. Durum, Academic Press Ltd. ftp site: ftp.harcourtbrace.com; directory: /pub/academic_press/saved/cytokineDB; password: 'anonymous'.

Martins-Green, M. (2000) Dynamics of cell-ECM interactions with implications for tissue engineering. In Principles of Tissue Engineering. 2nd Edition, eds. R.P. Lanza, W.L. Chick and R. Langer. R.G. Landes Co. (invited). pp33-55

Melkonian, G., C. Li, W. Zheng, P. Talbot, M. Martins-Green (2000). Normal patterns of angiogenesis and extracellular matrix deposition in chick chorioallantoic membranes are disrupted by mainstream and sidestream cigarette smoke. Toxicology and Applied Pharmacology 163(1):26-37.

Martins-Green, M., J. L. Bixby, T. Yamamoto, T. Graf and M. Sudol (2000). Tissue specific expression of Yrk kinase: Implications for differentiation and inflammation. International J. of Biochem. and Cell Biol. 32:351-364.

Li, QJ., S. Vaingankar, F. Sladek, M. Martins-Green (2000). Novel nuclear target for thrombin: Activation of the Elk1 transcription factor leads to chemokine gene expression. Blood 96(12):3692-3702.

Li, QJ., S. Lu, R. Ye and M. Martins-Green (2000). Isolation and characterization of a novel CXC chemokine receptor gene. Gene 257:307-317.

Liang, TS, JK Hartt, S. Lu, M. Martins-Green, J-L Gao, PM Murphy (2001). Cloning, mRNA distribution, and functional expression of an avian counterpart of the chemokine receptor/HIV coreceptor CXCR4. J. Leukocyte Biol. 69:297-305.

Martins-Green, M. (2001). The chicken Chemotactic and Angiogenic Factor, a CXC chemokine. Special Issue on Angiogenesis, J. Laurent and L. Claesson-Welsh (eds). International J. of Biochem. and Cell Biol. 33:427-432.

Feugate, J.E. and M. Martins-Green. (2002) The CXC chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure in vivo. J. Cell Biol 156:161-172.