Cancer and Inflammation Program

Director
Giorgio Trinchieri, M.D.
Deputy Director of Basic Research
Daniel W. McVicar, Ph.D.
Deputy Director of Translational Research
David A. Wink, Jr., Ph.D.

The Cancer and Inflammation Program (CIP) constitutes the major immunologic component of the CCR's inflammation and cancer initiative, which spans the NCI's campuses in Frederick and Bethesda and seeks to partner NCI's expertise in inflammation and immunology with its cutting-edge cancer etiology and carcinogenesis program.

Recent studies are shedding a new light on how innate resistance, as an integral part of inflammation, and adaptive immunity participate in oncogenesis and tumor surveillance. For a long time, innate resistance was considered a primitive nonspecific form of resistance to infections that was eclipsed by the potent and specific acquired immunity of higher organisms.

More recently, it has been recognized that innate resistance is not only the first line of defense against infections but also sets the stage and is necessary for the development of adaptive immunity. Advances in cancer biology now reveal that what used to be considered the defensive mechanisms of innate resistance and inflammation are indeed manifestations of tissue homeostasis and control of cellular proliferation that have many pleiotropic effects on carcinogenesis and tumor progression and dissemination. The interaction of the inflammatory mediators and effector cells with carcinogenesis and tumor progression is complicated and results in effects that either favor or impede tumor progression.

The Cancer and Inflammation Program is composed of 17 research sections:

- The Molecular Immunology Section (Dr. Steve Anderson) investigates the mechanisms controlling selective gene activation in the immune system.

- The HLA Immunogenetics Section (Dr. Mary Carrington) investigates the host genetic effects on human disease. The primary candidates include the HLA class I and II genes located within the human Major Histocompatibility Complex (MHC), because of their central role in the immune response.

- The Human Genetics Section (Dr. Michael Dean) is to develop methods for analyzing complex diseases and to apply them to human genetic conditions, such as cancer, HIV infection, and other diseases.

- The Protein Interactions Section (Dr. Dimiter Dimitrov) focuses on development of human monoclonal antibodies including isolated engineered antibody domains for prevention and treatment of cancer and other diseases.

- The Cytokines and Immunity Section (Dr. Scott Durum) is investigating the role of cytokines such as IL7 in the development of T lymphocyte and natural killer cell lineages and their role in promoting cell survival, terminal differentiation and apoptotic cell death.

- The Inflammation and Tumorigenesis Section (Dr. Yingling Hu) studies the mechanism of skin tumorigenesis, the effect of inflammatory microenvironments on skin tumorigenesis in the absence of IKKalpha, and the role of IKKalpha in the development of lymph cells and organs.

- The Immune Modulation Section (Dr. Dennis Klinman) studies immunostimulatory and immunosuppressive agents, their ability to alter the immune milieu, and their impact on the development of inflammatory and oncogenic processes.

- The Leukocyte Signaling Section (Dr. Daniel McVicar) dissects the signaling cascades of leukocyte regulatory receptors including the TREM, KIR, and Ly49s toward an understanding of the mechanisms underlying the innate immune system role in the development of, and subsequent response to, cancer.

- The Computational Structural Biology Section (Dr. Ruth Nussinov) is focusing on the key role and principles of allostery under normal conditions, in disease and in allosteric drug discovery.

- The Cellular Immunology Section (Dr. Joost Oppenheim) is studying the structure/function relationships of the family of chemoattractant cytokines. These investigators are investigating the role of chemokines in inflammation, immunity, and chemokine mimics such as defensins and autoantigens. They are also investigating the regulation of angiogenesis by chemokines and identifying chemokine inhibitors and immuno-regulatory molecules present in natural products. The investigators in this Section are also investigating the pathophysiological consequences of receptor cross-talk in regulating the functions of receptors for pain and chemokines.

- The Molecular Immunotherapy Section (Dr. Thomas Sayers) studies the molecular amplification of apoptotic signaling in tumor cells by TNF family members, and assesses the therapeutic benefit of this molecular targeting approach alone or in combination with immunotherapy in various mouse tumor models

- The Cancer Immunobiology Section (Dr. Giorgio Trinchieri) studies the role of dendritic cells, other innate or adaptive effector cell types, and pro-inflammatory or immunoregulatory cytokines on carcinogenesis and cancer therapy.

- The Chemoattractant Receptor and Signal Section (Dr. Ji Ming Wang) is engaged in studies on the role of chemoattractant receptors such as FPR and FPRL-1 in the pathogenesis of neurodegenerative diseases and tumor progression of glioblastomas.

- The Molecular and Chemical Inflammation Section (Dr. David Wink) studies the role of redox biology in cancer progression and therapy. Specifically how small reactive molecules modulate inflammatory processes that promote disease progression and  the identification of new therapeutics for improved outcome.

- The Cellular and Molecular Immunology Section (Dr. Howard Young) studies the molecular mechanism(s) of cytokine-induced gene expression in leukocytes. A primary focus of research is on IFN-gamma, an important marker of inflammation and the host immune response.

CIP Adjunct Investigators

Dr. Li Yang (Head, Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics, CCR) is investigating the mechanisms of tumor-host interaction underlying tumor initiation, invasion and metastasis, with the emphasis on the contribution of TGF-beta signaling and the COX-2 pathway.

CIP Core Facilities

The Cancer and Inflammation Program also supervises 3 core laboratories:

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Postdoctoral Fellow Scott Durum

durums@mail.ncifcrf.gov

301-846-1545

Immunology, T cells, leukemia, inflammatory bowel disease

1
Postdoctoral Fellow Charles Lin

Linp3@mail.nih.gov

301-846-6636

angiogenesis, vascular biology

2

About

The Cancer and Inflammation Program (CIP) constitutes the major immunologic component of the CCR's inflammation and cancer initiative, which spans the NCI's campuses in Frederick and Bethesda and seeks to partner NCI's expertise in inflammation and immunology with its cutting-edge cancer etiology and carcinogenesis program.

Recent studies are shedding a new light on how innate resistance, as an integral part of inflammation, and adaptive immunity participate in oncogenesis and tumor surveillance. For a long time, innate resistance was considered a primitive nonspecific form of resistance to infections that was eclipsed by the potent and specific acquired immunity of higher organisms.

More recently, it has been recognized that innate resistance is not only the first line of defense against infections but also sets the stage and is necessary for the development of adaptive immunity. Advances in cancer biology now reveal that what used to be considered the defensive mechanisms of innate resistance and inflammation are indeed manifestations of tissue homeostasis and control of cellular proliferation that have many pleiotropic effects on carcinogenesis and tumor progression and dissemination. The interaction of the inflammatory mediators and effector cells with carcinogenesis and tumor progression is complicated and results in effects that either favor or impede tumor progression.

The Cancer and Inflammation Program is composed of 17 research sections:

- The Molecular Immunology Section (Dr. Steve Anderson) investigates the mechanisms controlling selective gene activation in the immune system.

- The HLA Immunogenetics Section (Dr. Mary Carrington) investigates the host genetic effects on human disease. The primary candidates include the HLA class I and II genes located within the human Major Histocompatibility Complex (MHC), because of their central role in the immune response.

- The Human Genetics Section (Dr. Michael Dean) is to develop methods for analyzing complex diseases and to apply them to human genetic conditions, such as cancer, HIV infection, and other diseases.

- The Protein Interactions Section (Dr. Dimiter Dimitrov) focuses on development of human monoclonal antibodies including isolated engineered antibody domains for prevention and treatment of cancer and other diseases.

- The Cytokines and Immunity Section (Dr. Scott Durum) is investigating the role of cytokines such as IL7 in the development of T lymphocyte and natural killer cell lineages and their role in promoting cell survival, terminal differentiation and apoptotic cell death.

- The Inflammation and Tumorigenesis Section (Dr. Yingling Hu) studies the mechanism of skin tumorigenesis, the effect of inflammatory microenvironments on skin tumorigenesis in the absence of IKKalpha, and the role of IKKalpha in the development of lymph cells and organs.

- The Immune Modulation Section (Dr. Dennis Klinman) studies immunostimulatory and immunosuppressive agents, their ability to alter the immune milieu, and their impact on the development of inflammatory and oncogenic processes.

- The Leukocyte Signaling Section (Dr. Daniel McVicar) dissects the signaling cascades of leukocyte regulatory receptors including the TREM, KIR, and Ly49s toward an understanding of the mechanisms underlying the innate immune system role in the development of, and subsequent response to, cancer.

- The Computational Structural Biology Section (Dr. Ruth Nussinov) is focusing on the key role and principles of allostery under normal conditions, in disease and in allosteric drug discovery.

- The Cellular Immunology Section (Dr. Joost Oppenheim) is studying the structure/function relationships of the family of chemoattractant cytokines. These investigators are investigating the role of chemokines in inflammation, immunity, and chemokine mimics such as defensins and autoantigens. They are also investigating the regulation of angiogenesis by chemokines and identifying chemokine inhibitors and immuno-regulatory molecules present in natural products. The investigators in this Section are also investigating the pathophysiological consequences of receptor cross-talk in regulating the functions of receptors for pain and chemokines.

- The Molecular Immunotherapy Section (Dr. Thomas Sayers) studies the molecular amplification of apoptotic signaling in tumor cells by TNF family members, and assesses the therapeutic benefit of this molecular targeting approach alone or in combination with immunotherapy in various mouse tumor models

- The Cancer Immunobiology Section (Dr. Giorgio Trinchieri) studies the role of dendritic cells, other innate or adaptive effector cell types, and pro-inflammatory or immunoregulatory cytokines on carcinogenesis and cancer therapy.

- The Chemoattractant Receptor and Signal Section (Dr. Ji Ming Wang) is engaged in studies on the role of chemoattractant receptors such as FPR and FPRL-1 in the pathogenesis of neurodegenerative diseases and tumor progression of glioblastomas.

- The Molecular and Chemical Inflammation Section (Dr. David Wink) studies the role of redox biology in cancer progression and therapy. Specifically how small reactive molecules modulate inflammatory processes that promote disease progression and  the identification of new therapeutics for improved outcome.

- The Cellular and Molecular Immunology Section (Dr. Howard Young) studies the molecular mechanism(s) of cytokine-induced gene expression in leukocytes. A primary focus of research is on IFN-gamma, an important marker of inflammation and the host immune response.

CIP Adjunct Investigators

Dr. Li Yang (Head, Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics, CCR) is investigating the mechanisms of tumor-host interaction underlying tumor initiation, invasion and metastasis, with the emphasis on the contribution of TGF-beta signaling and the COX-2 pathway.

CIP Core Facilities

The Cancer and Inflammation Program also supervises 3 core laboratories:

PI & Key Staff

Positions

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Postdoctoral Fellow Scott Durum

durums@mail.ncifcrf.gov

301-846-1545

Immunology, T cells, leukemia, inflammatory bowel disease

1
Postdoctoral Fellow Charles Lin

Linp3@mail.nih.gov

301-846-6636

angiogenesis, vascular biology

2

Contact Info

Cancer and Inflammation Program
Center for Cancer Research
National Cancer Institute
Building 560, Room 31-93
Frederick, MD 21701-1201
Ph: 301-846-1323 or 301-846-7558
Fax: 301-846-1673
Administrative Lab Manager
301-846-5398
Secretary
301-846-5833
Secretary
301-846-1735
Secretary
301-846-1298
Secretary (Bldg. 37)
301-496-1450
Technical Lab Manager
301-846-1328