Immunology Graduate Program | University of California, San Francisco

Lisa Coussens, PhD

Inflammation, Proteolysis and Tissue Remodeling

Professor, Department of Pathology and
Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
513 Parnassus Ave, HSW 450C, Box 0502
San Francisco, CA 94143-0502

(415) 502-6378 (office)
(415) 514-0878 (FAX)
Email: lisa.coussens@ucsf.edu

Lab Website: http://cancer.ucsf.edu/coussens/index.php

Description of Research

The Coussens lab focuses on the role of inflammatory cells and proteases as critical regulators of skin, lung and breast cancer development. During the early development of cancer, many physiological processes occur in the vicinity of 'young tumor cells' that are similar to processes that occur during embryonic development and to healing of wounds in adult tissue, e.g., inflammation, angiogenesis (development of new blood supply) and tissue remodeling. During wound healing, inflammatory cells are recruited to sites of injury to eliminate potential bacterial infection as well as to facilitate healing by providing growth factors and proteases that are essential to the process. In so doing, a new blood supply is also formed that further helps the tissue heal. When 'healing' is complete, inflammation resolves and the tissue returns to its former state. Several of these parameters are conserved during tumor development; however, instead of initiating a 'healing' response, inflammatory cells provide growth-promoting factors that help tumors grow. By studying mouse models of skin, lung and breast cancer development, the Coussens lab is identifying important molecules involved in regulating tumor-associated inflammation and angiogenesis. Identification of these important regulatory mechanisms reveals drug-targets that can then be used to design novel therapeutic strategies for treating cancer development in humans.

Featured Papers
Tumor Stroma and Regulation of Cancer Development. Download Paper

De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Download Paper

Paradoxical roles of the immune system during cancer development. Download Paper

Distinctive Features of Angiogenesis and Lymphangiogenesis determin their funcitonality during De Novo Tumor Development. Download Paper

CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages. Download Paper

Coussens LM, Hanahan D, Arbeit J. (1996) Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. Am. J. Pathol. 149:1899-1917.

Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, Caughey, GH, Hanahan D. (1999) Inflammatory mast cells upregulate angiogenesis during squamous epithelial carcinogenesis. Genes & Development 13:1382-1397.

Coussens LM, Tinkle CL, Hanahan DH, Werb Z. (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481-490.

Coussens LM, Fingleton B, Matrisian LM. (2002) Matrix metalloproteinases and cancer: Trials and tribulations. Science 295:2387-2392.

Coussens LM, Werb Z. (2002) Inflammation and cancer. Nature 420: 860-867.

Daniel D, Meyer-Morse N, Bergsland EK, Dehne K, Coussens LM, Hanahan D. (2003) Immune enhancement of skin carcinogenesis by CD4 + T cells. J Exp. Med, 197:1017-1028.

Rhee JS, Diaz R, Korets L, Hogson G, Coussens LM. (2004) TIMP-1 alters susceptibility to carcinogenesis. Cancer Research 64:952-961.

de Visser KE, Korets LV, Coussens LM. (2004) Early neoplastic progression is complement-independent. Neoplasia 6: 768-776.

de Visser KE, Korets LV, Coussens LM. (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7:411-423.

Tlsty TD, Coussens LM. (2006) Tumor stroma and regulation of cancer development. Ann Rev Pathol. Mech of Disease, 1: 119-150.

Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. (2007) Curr Opin Immunology 19(2), 209-216.

Egeblad M, Shen HCJ, Behonick DJ, Wilmes L, Eichten A, Korets L, Kheradmand F, Werb Z, Coussens LM. (2007). Type I collagen is a modifier of matrix metalloproteinase 2 function in skeletal development. Dev Dynamics, 36:1683-1693.

Eichten AE, Hyun WC, Coussens LM. (2007) Distinctive features of angiogenesis and lymphangiogenesis determine their functionality during de novo tumor development. Cancer Research, 67:5211-5220.

DeNardo DG, Johansson M, Coussens LM. (2008) Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev.27:11-18.

Johansson M, DeNardo DG, Coussens LM. (2008) Polarized immune responses differentially regulate cancer development. Immunol Rev., 222:145-154.

Kenny H, Kaur S, Coussens LM, Lengyel E. (2008) Adhesion of OvCa cells to peritoneum is mediated by MMP-2 cleavage of fibronectin, J Clin Invest. 118(4):1367-1379.

Watkins GA, Jones EF, Shell MS, VanBrocklin HV, Pan MH, Hanrahan SM, Feng JJ, He J, Sounni NE, Dill KA, Contag CH, Coussens LM, Franc BL. (2009) Development of an optimized activatable MMP-14 targeted SPECT imaging probe. Bioorganic & Medicinal Chemistry, 17:653-659.

DeNardo DG, Baretto JB, Andreu P, Vasquez L, Kolhatkar N, Coussens LM. (2009) CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell, 16:91-102.