The Integrated Therapies Laboratory is a collaborative research effort between Michael J. Gough, Ph.D., and Marka R. Crittenden, M.D., Ph.D. It encompasses their overlapping research interest into the ability of cytotoxic therapy to provide large-scale cancer cell death in vivo, while modifying the profile of immune cells within the tumor. Research projects in the Integrative Therapies Laboratory are investigating the interaction between cytotoxic therapy-induced cancer cell death and the innate and adaptive immune system of the patient.
Current Projects
Cancer patients receive treatment with some combination of surgery, radiation and chemotherapy, and we have reason to believe that the patient’s own immune system may play a role in the success and in the failure of these therapies. As cancers progress, an array of non-cancer cells are co-opted or recruited into the tumor environment. The tumor macrophage is one of the more important cells in this mix since it influences many aspects of the tumor environment. One of our aims is to target the macrophages in the tumor to remove their inhibitory effects and create an environment that supports rather than opposes anti-tumor immune responses.
To achieve this aim, we make use of the observation that not all cell death is created equal. As cytotoxic therapies kill cancer cells, other cells, particularly macrophages, internalize and destroy the remnants. However, certain modes of catastrophic cell death also release cellular contents that activate inflammatory processes in macrophages that can aid immune responses. Despite such potential adjuvant activity, we have identified that the dysregulated macrophages of the tumor environment respond to inflammatory stimuli with further immune suppression. We are developing strategies to overcome these tumor-supportive and immune-suppressive macrophages through a range of molecular techniques. The goal of this project is to redirect the inflammatory processes that have been subverted to support tumor growth and use the power of the patient’s own immune system to target and destroy the residual cancer cells that remain following treatment.
Research projects in the Integrated Therapies Laboratory encompass basic research, pre-clinical therapy models and translational research through a multi-disciplinary team of scientists, physicians and physician-scientists to bring novel cancer therapy options to patients.
Current Research Collaborations
Marka R. Crittenden, M.D., Ph.D., director of translational radiation research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center; radiation oncologist, The Oregon Clinic
Steven K. Seung, M.D., Ph.D., director of radiation research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center; radiation oncologist, The Oregon Clinic
Todd Crocenzi, M.D., director, gastrointestinal oncology research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center; medical oncologist
Andrew M. Jackson, Ph.D., Academic Oncology, University of Nottingham, City Hospital, Nottingham, UK
Paul D. Hansen, M.D., F.A.C.S., medical director, Providence Hepatobiliary and Pancreatic Cancer Program; Gastrointestinal & Minimally Invasive Surgery Division, The Oregon Clinic
Full List of Publications
Laboratory Team
Michael J. Gough, Ph.D.
Marka R. Crittenden, M.D., Ph.D.
Benjamin Cottam
Philippa Newell, M.D.
Talicia Savage