lisa.coussens@ucsf.edu
(415) 514-0231 (lab); (415) 514-0878 (fax)

Box 0502, UCSF; San Francisco, CA 94143-0502

deliveries: 513 Parnassus Ave, HSW-425; San Francisco, CA 94143

Full Biosketch

Nesrine Affara, PhD; Pauline Andreu, PhD; Jairo Barreto, MD; David DeNardo, PhD; Preethi Ganesan, MD; Magnus Johansson, PhD; Nikita Kolhatkar, BS; Lidiya Korets, BA (mouse colony mgr.); Brian Ruffell, PhD; Jane Wiesen, PhD (lab mgr.)

Inflammation, Proteolysis, Tissue Remodeling and Cancer Development

The Coussens lab focuses on the role of inflammatory cells and leukocyte 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.

The concept that leukocytes are components of malignant tumors is not new; however, their functional involvement as promoting forces for tumor progression has only recently been appreciated. We are interested in understanding the molecular mechanisms that regulate leukocyte recruitment into neoplastic tissue and subsequent regulation those leukocytes exert on evolving cancer cells. To address these issues, we have taken several approaches to investigate mechanisms involved in: i. induction and maintenance of chronic inflammatory microenvironments in premalignant tissues, ii. role of leukocyte proteases as regulators of cancer development, and iii. development of novel non-invasive imaging reagents to monitor and/or delivery radiotherapeutics to carcinoma cells. Our studies are designed to test the hypothesis that inflammation is a critical parameter of neoplastic development and therefore represents an efficacious target for anti-cancer therapies. By studying mouse models of skin, lung and breast cancer development, the Coussens lab is identifying important molecules involved in regulating tumor-associated inflammation, angiogenesis, and cancer development. 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.

de Visser KE, Korets LV, and Coussens LM, De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent, Cancer Cell. 2005 May;7(5):411-23. [link]

de Visser KE, Eichten A and Coussens LM, Paradoxical roles of the immune system during cancer development, Nat Rev Cancer. 2006 Jan;6(1):24-37. [link]

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

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. [link]

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. [link]