Edus Houston Warren

Appointments and Affiliations

 
 
Fred Hutchinson Cancer Research Center
Clinical Research Division
Program in Immunology
Associate Member
University of Washington
School of Medicine
Medicine
Medical Oncology
Associate Professor
Professional Headshot of Edus Houston Warren

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N.
P.O. Box 19024
D3-100
Seattle, Washington 98109-1024
United States

Contact

Phone: (206) 667-6441
Fax: (206) 667-7983
Mobile: (206) 390-0874
ehwarren@u.washington.edu
http://labs.fhcrc.org/warren/index.html
 

Degrees

M.D., Harvard University, 1991.
Ph.D., Harvard University, Neurobiology, 1988.
A.B., Harvard University, Applied Mathematics, 1982.

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.

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

  • 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.

 

Recent Publications

2013
2012
Chapman, M, Warren EH, Wu CJ.  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. Abstract
2011
Falkenburg, FJH, Warren EH.  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.
Grogan, BM, Tabellini L, Storer BE, Bumgarner TE, Astigarraga CC, Flowers MED, Lee SJ, Martin PJ, Warren EH, Hansen JA.  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. Abstract
2010
2009