Dr. Edus Houston Warren |
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Fred Hutchinson Cancer Research Center Clinical Research Division Program in Immunology Associate Member University of Washington School of Medicine Medicine Medical Oncology Associate Professor |  |
Mailing AddressFred Hutchinson Cancer Research Center 1100 Fairview Avenue N. P.O. Box 19024 D3-100 Seattle, Washington 98109-1024United States | Contact Information |
Qualifications
M.D., Harvard University, 1991.
Ph.D., Harvard University, Neurobiology, 1988.
A.B., Harvard University, Applied Mathematics, 1982.
Expertise and Research Interests
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.
Future Research
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.
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.
Keywords
COS Keywords:
'Malaria', Cancer or Carcinogenesis, Cell Transplantation, Hematology, Immunology, Immunotherapy, Neurobiology, Oncology.Additional Terms:
Oncology.Languages
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Functional, Functional, Functional)
German: (Basic, Basic, Basic)
Spanish: (Basic, Basic, Basic)
Memberships
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
Previous Positions
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
Funding Received
- National Institutes of Health (NIH): P01 CA 18029-31 (Appelbaum) Improve the outcome of allogeneic hematopoietic stem cell transplantation in the treatment of hematologic malignancies, 2007 to 2012.
- University of Washington Royalty Research Fund: 3896 (Warren) Identification of genomic loci associated with graft-versus-leukemia activity after allogeneic hematopoietic cell transplantation, 2007 to 2008.
- National Institutes of Health (NIH): 5 P30 CA015704-34 (Hartwell) FHCRC CCSG Pilot (Warren) Characterization of tumor-and lymph node-infiltrating CD3* lymphocytes in stage III colorectal carcinoma, 2007 to 2007.
- J. Orin Edson Fund for Immunotherapy (Warren): Characterization fo tumor-and lymph node-infiltrating CD3* lymphocytes in stage III colorectal carcinoma, 2007 to 2007.
- National Institutes of Health (NIH): R21 CA119599-01 (Deeg) WI1 Expression in patients treated with MDS treat with ATG and TNF-a blockade, 2005 to 2007.
- Lauri Strauss Leukemia Foundation: FDN TE 4153 (Warren) Transcription factors in hematopoietic stem cells as targets for leukemia immunotherapy, 2005 to 2006.
- National Institutes of Health (NIH): Allogeneic T Cell Responses Against Renal Cell Carcinoma, 1 R01 CA106512 (PI), 2004 to 2009.
- Damon Runyon Cancer Research Foundation: FND TE 3172 (Warren) Antigen-specific T-cell therapy for leukemia, 2000 to 2005.
Publications
- Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR (Jan 2010) Therapy of relapsed leukemia after allogeneic hematopoietic cell transplant with T cells specific for minor histocompatibility antigens., Blood, In Press
- Campregher PV, Srivastava SK, Deeg HJ, Robins HS, Warren EH (Jan 2010) Abnormalities of the alphabeta T cell receptor repertoire in advanced myelodysplastic syndrome., Experimental Hematology, In Press
- McCarroll SA, Bradner JE, Turpeinen H, Volin L, Martin PJ, Chilewski SD, Antin JH, Lee SJ, Ruutu T, Storer B, Warren EH, Zhang B, Zhao LP, Ginsburg D, Soiffer RJ, Partanen J, Hansen JA, Ritz J, Palotie A, Altshuler D (Dec 2009) Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease., Nature Genetics, 41 (12), 1341-4
- Tykodi SS, Voong LN, Warren EH (Dec 2009) Combining allogeneic immunotherapy with an mTOR inhibitor for advanced renal cell carcinoma., Bone Marrow Transplantation, In Press
- Robins HS, Campregher PV, Srivastava SK, Wacher A, Turtle CJ, Kahsai O, Riddell SR, Warren EH, Carlson CS (Nov 2009) Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells., Blood, 114 (19), 4099-107
- Warren EH (Sep 2009) Genetic risk for colitis-associated colorectal cancer., Gut, 58 (9), 1177-9
- Spellman S, Warden MB, Haagenson M, Pietz BC, Goulmy E, Warren EH, Wang T, Ellis TM (Jul 2009) Effects of mismatching for minor histocompatibility antigens on clinical outcomes in HLA-matched, unrelated hematopoietic stem cell transplants., Biology of Blood and Marrow Transplantation, 15 (7), 856-63
- Nishida T, Hudecek M, Kostic A, Bleakley M, Warren EH, Maloney D, Storb R, Riddell SR (Jul 2009) Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia., Clinical Cancer Research, 15 (14), 4759-68
- Vigorito AC, Campregher PV, Storer BE, Carpenter PA, Moravec CK, Kiem HP, Fero ML, Warren EH, Lee SJ, Appelbaum FR, Martin PJ, Flowers ME (Jul 2009) Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD., Blood, 114 (3), 702-8
- Chien JW, Zhao LP, Storer B, Martin PJ, Boeckh M, Warren EH, Hansen JA (Jan 2009) Improving hematopoietic cell transplant outcomes in a new era of genomic research., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 15 (1 Suppl), 42-5
- Flowers ME, Storer B, Carpenter P, Rezvani AR, Vigorito AC, Campregher PV, Moravec C, Kiem HP, Fero M, Georges G, Warren E, Lee S, Sanders JE, Appelbaum F, Martin PJ (Dec 2008) Treatment change as a predictor of outcome among patients with classic chronic graft-versus-host disease., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 14 (12), 1380-4
- Tykodi SS, Fujii N, Vigneron N, Lu SM, Mito JK, Miranda MX, Chou J, Voong LN, Thompson JA, Sandmaier BM, Cresswell P, Van den Eynde B, Riddell SR, Warren EH (Aug 2008) C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients., Clinical cancer research : an official journal of the American Association for Cancer Research, 14 (16), 5260-9
- Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH (May 2008) DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells., Blood, 111 (9), 4817-26
- Campregher PV, Gooley T, Scott BL, Moravec C, Sandmaier B, Martin PJ, Deeg HJ, Warren EH, Flowers ME (Nov 2007) Results of donor lymphocyte infusions for relapsed myelodysplastic syndrome after hematopoietic cell transplantation., Bone marrow transplantation, 40 (10), 965-71
- Terakura S, Murata M, Warren EH, Sette A, Sidney J, Naoe T, Riddell SR (May 2007) A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403., Transplantation, 83 (9), 1242-8
- Deeg HJ, Maris MB, Scott BL, Warren EH (Oct 2006) Optimization of allogeneic transplant conditioning: not the time for dogma., Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, 20 (10), 1701-5
- Warren EH, Vigneron NJ, Gavin MA, Coulie PG, Stroobant V, Dalet A, Tykodi SS, Xuereb SM, Mito JK, Riddell SR, Van den Eynde BJ (Sep 2006) An antigen produced by splicing of noncontiguous peptides in the reverse order., Science (New York, N.Y.), 313 (5792), 1444-7
- Brickner AG, Evans AM, Mito JK, Xuereb SM, Feng X, Nishida T, Fairfull L, Ferrell RE, Foon KA, Hunt DF, Shabanowitz J, Engelhard VH, Riddell SR, Warren EH (May 2006) The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL., Blood, 107 (9), 3779-86
- Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, Heimfeld S, Flowers ME, Anasetti C, Doney KC, Hansen JA, Kiem HP, Nash RA, O'Donnell PV, Radich JP, Sandmaier BM, Scott BL, Sorror ML, Warren EH, Witherspoon RP, Woolfrey A, Appelbaum FR, Storb R (May 2006) Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 12 (5), 573-84
- Berger C, Flowers ME, Warren EH, Riddell SR. (2006) Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation, Blood, 107, 2294-2302
- Warren EH (2006) Minor histocmpatibility antigens in allogeneic hematopoietic cell transplantation, Current Opinion in Organ Transplantation, 11, 31-36
- Riddell SR, Bleakley M, Nishida T, Berger C, Warren EH (Jan 2006) Adoptive transfer of allogeneic antigen-specific T cells., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 12 (1 Suppl 1), 9-12
- Tykodi SS, Warren EH, Thompson JA, Riddell SR, Childs RW, Otterud BE, Leppert MF, Storb R, Sandmaier BM, Allogeneic Hematopoietic Cell Transplantation for Metastatic Renal Cell
Carcinoma After Nonmyeloablative Conditioning: Toxicity, Clinical
Response, and Immunological Response to Minor Histocompatibility
Antigens., Clinical Cancer Research : An Official Journal of the American Association for Cancer Research., 10(23), 7799-811, Dec 2004
- Torikai H, Akatsuka Y, Miyazaki M, Warren EH, Oba T, Tsujimura K, Motoyoshi K, Morishima Y, Kodera Y, Kuzushima K, Takahashi T (Dec 2004) A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene., Journal of Immunology, 173 (11), 7046-54
- Randolph SS, Gooley TA, Warren EH, Appelbaum FR, Riddell SR, Female donors contribute to a selective graft-versus-leukemia effect in
male recipients of HLA-matched, related hematopoietic stem cell
transplants, Blood, 103(1), 347-52, January 2004
- Deeg HJ, Gooley TA, Flowers ME, Sale GE, Slattery JT, Anasetti C, Chauncey TR, Doney K, Georges GE, Kiem HP, Martin PJ, Petersdorf EW, Radich J, Sanders JE, Sandmaier BM, Warren EH, Witherspoon RP, Storb R, Appelbaum FR, Allogeneic hematopoietic stem cell transplantation for myelofibrosis, Blood, 102(12), 3912-8, December 2003
- Akatsuka Y, Warren EH, Gooley TA, Brickner AG, Lin MT, Hansen JA, Martin PJ, Madtes DK, Engelhard VH, Takahashi T, Riddell SR, Disparity for a newly identified minor histocompatibility antigen, HA-8,
correlates with acute graft-versus-host disease after haematopoietic stem
cell transplantation from an HLA-identica, British Journal of Haematology, 123(4), 671-5, November 2003
- Riddell SR, Berger C, Murata M, Randolph S, Warren EH, The graft versus leukemia response after allogeneic hematopoietic stem cell transplantation, Blood Reviews, 17(3), 153-62, September 2003
- Murata M, Warren EH, Riddell SR, A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion, Journal of Experimental Medicine, 197(10), 1279-89, May 2003
- Warren EH, Otterud BE, Linterman RW, Brickner AG, Engelhard VH, Leppert MF, Martin PJ, Riddell SR, Feasibility of using genetic linkage analysis to identify the genes encoding T cell-defined minor histocompatibility antigens, Tissue Antigens, 59(4), 293-303, April 2002
- Riddell SR, Murata M, Bryant S, Warren EH, T-cell therapy of leukemia, Cancer Control : Journal of the Moffitt Cancer Center, 9(2), 114-22, 2002
- Brickner AG, Warren EH, Caldwell JA, Akatsuka Y, Golovina TN, Zarling AL, Shabanowitz J, Eisenlohr LC, Hunt DF, Engelhard VH, Riddell SR, The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing, Journal of Experimental Medicine, 193(2), 195-206, 2001
- Warren EH, Gavin MA, Simpson E, Chandler P, Page DC, Disteche C, Stankey KA, Greenberg PD, Riddell SR, The human UTY gene encodes a novel HLA-B8-restricted H-Y antigen, Journal of Immunology, 164(5), 2807-14, 2000
- Bonnet D, Warren EH, Greenberg PD, Dick JE, Riddell SR, CD8 minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells, Proceedings of the National Academy of Sciences (USA), 96(15), 8639-44, 1999
- Warren EH, Gavin M, Greenberg PD, Riddell SR, Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation, Current Opinion in Hematology, 5(6), 429-33, November 1998
- Warren EH, Greenberg PD, Riddell SR, Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution, Blood, 91(6), 2197-207, 1998
Profile Details
Last Updated: 1/27/2010
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