OHSU

Coussens Lab

Research

CD31_Hypoxia_CC3-in-PyMT

Immunofluorescent image of a murine mammary carcinoma displaying vasculature (blue), regions of hypoxia (green), and areas of cell death (red).

The Coussens lab focuses on the role of immune cells and their mediators as critical regulators of 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., leukocyte recruitment and activation (inflammation), angiogenesis (development of new blood supply) and tissue remodeling.  During tumor development however, instead of initiating a 'healing' response, activated leukocytes provide growth-promoting factors that typically help tumors grow.  We are interested in understanding the molecular and cellular mechanisms that regulate leukocyte recruitment into neoplastic tissue, and the 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, malignant and metastatic tissues using murine models of human cancer development, and clinical samples obtained fresh from the operating room from patients with cancer, ii. role of leukocytes in regulating tissue remodeling, angiogenesis, immune suppression and cancer development, iii. development of novel non-invasive imaging reagents to monitor immune response in tissues/tumors.  The long-term goal of this work is to translate basic observations made in the mouse, toward rational design of novel therapeutics whose aim will be to block and/or alter rate-limiting events critical for solid tumor growth, maintenance or recurrence in humans, and/or therapeutics that enhance the efficacy of standard-of-care cytotoxic therapy.  Currently, we are actively utilizing transgenic mouse models of solid tumor development (non-small cell lung cancer, non-melanoma squamous, pancreatic and breast adenocarcinoma, and mesothelioma) to reveal the functional roles of adaptive and innate leukocytes during tumor development.  These experimental studies are conducted in parallel with evaluation of representative human cancer specimens to affirm that mechanisms revealed in the experimental setting represent fundamental parameters of multi-stage cancer development in humans.


Laboratory Manager / Research Coordinator

Jane Wiesen PhD

Jane Wiesen, Ph.D.

Education: Ph.D., Cellular and Molecular Biology, University of Michigan, 1992

Postdoctoral training: The University of California, San Francisco, Departments of OB/GYN and Anatomy


Research Assistant Professors

Sushil Kumar PhD

Sushil Kumar, Ph.D.

Education: Ph.D., Max Planck Institute of Biochemistry, Munich, Germany, 2007

Postdoctoral training: Institute of Molecular Cancer Research, University of Zurich, Switzerland, 2008 - 2011;  Oregon Health & Science University 2012 - 2014

Scientific interests: My scientific interests are to understand the molecular basis of tumor related inflammation and translation of this knowledge into modern cancer therapy.


Brian Ruffell PhD

Brian Ruffell, Ph.D.

Education: Ph.D., Department of Microbiology and Immunology, University of British Columbia, 2008

Postdoctoral training:  The University of California, San Francisco 2008 - 2012; Oregon Health & Science University, 2012 - 2013

Scientific interests: Immune suppression within the tumor microenvironment with the goal of improving the efficacy of chemotherapeutics and immunotherapies.


Postdoctoral Scholars

Andrew Gunderson  PhD

Andrew Gunderson, Ph.D.

Education: Ph.D., Immunology and Infectious Disease Program, The Pennsylvania State University, 2012

Scientific interests: Patients with pancreatic ductal adenocarcinomas (PDAC) have extremely poor survival rates of ~ 5% after five years and chronic pancreatitis is a known risk factor for invasive malignant progression. I am interested in characterizing the infiltration of immune subsets into human pancreatic neoplasms at various stages and correlating these results to genetic defects in specific tumor suppressor pathways in order to establish a direct casual link between mutational status, inflammatory response, and disease prognosis. This work is aimed at identifying novel immune targets for PDAC therapies.


Terry resized

Terry Medler, Ph.D.

Education: Ph.D., Department of Pathology, Northwestern University, 2012

Scientific interests: The skin acts as both a physical and immunological barrier to a barrage of environmental insults, such as UV radiation, chemical carcinogens, and oncogenic viruses. The damage response (inflammation) is mediated by both innate and adaptive immunity to clear damaged cells and pathogens such that tissue homeostasis can be restored. When inflammation fails to resolve and instead becomes chronic, it acts as a promoting force for neoplastic progression. My interests lie in identifying mechanisms by which immune cells foster cancer development such that novel targeted immunotherapies can be developed. Other interests include identifying mechanisms by which autoimmune skin disorders (pemphigus vulgaris) occur and discovering targeted immunotherapies to help ameliorate disease with fewer side effects.


Graduate Students

Charlie Gast-resized2

Charlie Gast 

Education:  M.D., Ph.D., (in progress), Cancer Biology, Oregon Health & Science University; B.A., Biochemistry/Molecular Biology, Lewis & Clark College (2006)

Scientific interests:  My research interests focus on the role macrophages play in promoting the progression of cancer.  Specifically, I am investigating phenotypic alterations in cancer that are a result of hybrid cells forming via fusion between cancer cells and macrophages.  Additionally, I am testing specific immunotherapies that target macrophage function to treat metastatic disease.  In my free time I enjoy hiking, skiing, brewing beer and changing diapers.


shannon-resized3

Education:  Ph.D. (in progress), Cancer Biology, Oregon Health & Science University; B.S., Molecular Biology, Portland State University (2012)

Scientific interests:  Chronic inflammation as a driver of neoplasia, pancreatitis & pancreatic ductal adenocarcinoma, acinar cell plasticity, pancreatic regeneration following injury


Laboratory Staff

Teresa Beechwood resize
Teresa Beechwood

Pat Flynn

Education:  B.S., Ecology and Evolutionary Biology, Western Washington University

Scientific interests:  Tumor associated inflammation, cancer immunotherapy, immunity regulation, autoimmunity, T cell biology


Jo Hill

Jo Hill

Education: Drexel University College of Medicine's Master's degree program in histotechnology.

Interests:  the integration of art & science, tissue ultrastructure, and the beauty of the natural world.  She is particularly intrigued with cell-to-cell connections (physical and chemical), and the intricacies of the cytoskeleton.


Justin Tibbitts

Justin Tibbits

Education: M.S., Biology, New Mexico Institute of Mining and Technology; M.B.A., Technology, University of New Mexico

Interests: family, cancer biology, geosciences, hockey, fishing and all things outdoors.


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