Edus Houston Warren
M.D., Harvard University, 1991.
Ph.D., Harvard University, Neurobiology, 1988.
A.B., Harvard University, Applied Mathematics, 1982.
My primary laboratory and clinical interest is the cellular and molecular dissection of antitumor immune responses, so that these immune responses can be exploited to clinical advantage. In particular, the research in my laboratory is focused on the mechanisms and target molecules associated with the graft-versus-tumor (GVT) reaction that occurs after allogeneic hematopoietic cell transplantation for hematologic malignancies and selected solid tumors. My lab has extensive experience with the characterization and manipulation of human CD8+ and CD4+ T cells, as well as with the identification of antigens recognized by CD8+ cytotoxic T lymphocyte (CTL) clones using a variety of techniques, including cDNA expression cloning, genetic linkage analysis, and peptide elution/HPLC fractionation. In the clinical realm, I have several years' of experience serving as the Principal Investigator on an IRB- and FDA-approved Phase I clinical trial of adoptive therapy with CD8+ minor histocompatibility antigen-specific CTL clones for the treatment of acute leukemia or high-grade myelodysplasia that recurs after HLA-identical allogeneic hematopoietic cell transplantation. I am an Attending Physician on the Allogeneic Transplant Service at the Seattle Cancer Care Alliance.
The major focus of research in the Warren lab is the dissection of human antitumor immune responses at the cellular and molecular level. Identification and characterization of the immune effector cells and molecules that mediate tumor regression or elimination, and characterization of the relevant antigens recognized on tumor cells, will provide the foundation for the development of immune therapies that can manipulate these antitumor immune responses to clinical advantage.
Current effort is centered in several interrelated areas. The graft-versus-tumor (GVT) effect that occurs in recipients of allogeneic hematopoietic cell transplants is the one of the clearest examples of successful immunotherapy in humans. The GVT effect is mediated primarily by CD8+ and CD4+ T lymphocytes contained in or derived from the donor hematopoietic cell graft, and much of the lab's current effort is dedicated to understanding the T cells that mediate the GVT effect and identifying their target antigens. A major class of these target antigens comprises minor histocompatibility antigens, which are short peptides encoded by polymorphic genes that are presented on the cell surface by MHC class I and II molecules. A related area of current research focus is the immunobiology of graft-versus-host disease (GVHD), with which the GVT effect is strongly associated, but which nonetheless causes significant morbidity and mortality after allogeneic hematopoietic cell transplantation; GVHD is one of the leading causes of treatment failure. A third area of current research focus is the dissection of autologous immune responses against kidney and colon cancer. Kidney cancer is a common solid tumor in adults and is distinguished from many other solid tumors by its responsiveness to immune-based therapies. The identification of tumor-specific and tumor-associated antigens expressed on the surface of kidney cancer cells that could potentially be targeted with T cell-based immunotherapy is an active program in the lab. Colon cancer is another common solid tumor against which effective immune-based therapies might in the future be crafted. Recent studies in numerous labs have demonstrated that the adaptive immune system has a profound influence on the natural history of colon cancer, and that CD8+ T lymphocytes infiltrating the primary tumor are central mediators of this antitumor immune response. The Warren lab is actively investigating the antigenic specificity and effector functions of tumor-reactive CD8+ T lymphocytes infiltrating primary human colon tumors.
In addition, Dr. Warren's laboratory is collaborating with the labs of Drs. Harlan Robins and Christopher Carlson in the Public Health Sciences Division at the FHCRC on the development of techniques utilizing massively parallel DNA sequencing technologies to define more comprehensively than ever before possible the T cell receptor (TCR) repertoire of complex T lymphocyte populations. Comprehensive analysis of T cell populations at the clonal level using these new technologies will provide valuable insights into the immunobiology of tumors and autoimmune disease and will have important applications to the design and analysis of vaccines against infectious diseases.
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Functional, Functional, Functional)
German: (Basic, Basic, Basic)
Spanish: (Basic, Basic, Basic)
American Association for the Advancement of Science
American Society for Clinical Oncology
American Society of Hematology
International Society for Cellular Therapy
Honors and Awards
2008-2013, Clinical Scientist Award in Translational Research, Burroughs Wellcome Fund
2000-2005, Lilly Clinical Investigator Award, Damon Runyon Cancer Research Foundation
1999-2000, Mentored Clinical Scientist Development (K08) Award, National Institutes of Health (NIH)
1996-1997, Florence A. Carter Fellowship in Leukemia Research, American Medical Association Education and Research Fund
1996-1998, International Fellowship in Research on Leukemia and Allied Diseases, Lady Tata Memorial Trust
1995-1995, Molecular Biology in Clinical Oncology Workship, American Association for Cancer Research
1979-1982, Harvard College Scholarship, Harvard College
1977-1977, National Merit Scholarship, Monsanto Corporation
2003-2004, Visiting Scientist, Ludwig Institute for Cancer Research, Brussels Branch
2001-2007, Assistant Professor of Medicine, University of Washington, Department of Medicine
2001-2007, Assistant Member, Fred Hutchinson Cancer Research Center, Program in Immunology, Clinical Research Division
1998-2001, Associate in Clinical Research, Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center
1997-2001, Acting Instructor, University of Washington, Department of Medicine
1996-1998, Research Associate, Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center
1993-1996, Fellow, Medical Oncology, University of Washington
1992-1993, Resident, Internal Medicine, Massachusetts General Hospital
1991-1992, Intern, Internal Medicine, Massachusetts General Hospital
Dynamics of the cytotoxic T cell response to a model of acute viral infection.. Journal of virology. 89(8):4517-26.. 2015.
Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in the MHC.. Gene therapy. 21(3):337-42.. 2014.
Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.. Journal for immunotherapy of cancer. 2(1):36.. 2014.
High-throughput sequencing of B- and T-lymphocyte antigen receptors in hematology.. Blood. 122(1):19-22.. 2013.
HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway.. Journal of immunology (Baltimore, Md. : 1950). 191(4):1567-77.. 2013.
Dissecting graft-versus-leukemia from graft-versus-host-disease using novel strategies.. Tissue antigens. 81(4):183-93.. 2013.
CD8+ T-cell clones specific for the 5T4 antigen target renal cell carcinoma tumor-initiating cells in a murine xenograft model.. Journal of immunotherapy (Hagerstown, Md. : 1997). 35(7):523-33.. 2012.
Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of allogeneic HCT.. Blood. 120(14):2796-2806.. 2012.
Diversifying the MHC peptide portfolio.. Blood. 120(16):3165-7.. 2012.
Evaluation of published single nucleotide polymorphisms associated with acute graft versus host disease. Blood. 119(22):5311-5319.. 2012.
Applications of next-generation sequencing to blood and marrow transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(1 Suppl):S151-60.. 2012.
Epigenetic Modulation to Enable Antigen-specific T-cell Therapy of Colorectal Cancer.. Journal of immunotherapy (Hagerstown, Md. : 1997). 35(2):131-41.. 2012.
A Phase I/II Study of Chemotherapy Followed by Donor Lymphocyte Infusion plus Interleukin-2 for Relapsed Acute Leukemia after Allogeneic Hematopoietic Cell Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(9):1308-15.. 2011.
Blazing a trail in T-cell recognition.. Blood. 117(18):4681-2.. 2011.
Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia: relapse-free survival is determined by karyotype and comorbidities.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(6):908-15.. 2011.
Allogeneic hematopoietic cell transplantation for renal cell carcinoma: ten years after.. Expert opinion on biological therapy. 11(6):763-73.. 2011.
Graft versus leukemia reactivity after allogeneic stem cell transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(1 Suppl):S33-8.. 2011.
Activation and expansion of CD8(+) T effector cells in patients with chronic graft-versus-host disease.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(8):1121-32.. 2011.
Overlap and effective size of the human CD8+ T cell receptor repertoire.. Science translational medicine. 2(47):47ra64.. 2010.