Megan Sykes, MD

  • Professor of Microbiology and Immunology and Surgical Sciences (in Surgery)
  • Michael J. Friedlander Professor of Medicine
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Overview

Megan Sykes’ research career, during which she has published >440 papers and book chapters, has focused on hematopoietic cell transplantation, organ allograft tolerance induction, xenotransplantation tolerance and Type 1 diabetes. Dr. Sykes has developed novel strategies for achieving graft-versus-tumor effects without graft-versus-host disease following hematopoietic cell transplantation (HCT). She developed an approach that has been evaluated in clinical trials of non-myeloablative haploidentical HCT whose safety and efficacy allowed trials of HCT for the induction of organ allograft tolerance, allowing intentional achievement of tolerance in humans for the first time. Dr. Sykes has dissected the tolerance mechanisms and pioneered minimal conditioning approaches for using HCT to achieve allograft and xenograft tolerance. Her work on xenogeneic thymic transplantation for tolerance induction has led, for the first time, to long-term kidney xenograft survival in non-human primates. She has extended the HCT approach to the problem of reversing autoimmunity while replacing destroyed islets of Langerhans in Type 1 diabetes. She has developed novel “humanized mouse” models that allow personalized analysis of human immune disorders and therapies. Dr. Sykes believes that a mechanistic understanding of manipulations used to achieve clinical goals is essential to the translation of these manipulations to the clinic. It is for this reason that she has consistently worked at the interface between basic science and clinical applications, and has been able to translate her research to new treatments for patients requiring bone marrow or organ transplants. Dr. Sykes is a Past President of the International Xenotransplantation Association, served as Vice President of TTS, has repeatedly served on TTS Council and is a member of the Institute of Medicine of the National Academies and of the Association of American Physicians. She has received many honors and awards, including the 2018 Medawar Prize.

In 2010, after 20 years at Massachusetts General Hospital and Harvard Medical School, Dr. Sykes moved to Columbia University to establish the Columbia Center for Translational Immunology (CCTI). The CCTI is a multidisciplinary research center whose scope includes transplantation (organ and bone marrow), autoimmune disease, tumor immunology, infectious immunity and basic immunology. Currently, the CCTI has a staff of >100 scientists and support staff, including 17 faculty members. Dr. Sykes' own laboratory program currently includes major projects in the area of xenograft tolerance induction in humanized mouse models; unique humanized mouse models for the analysis and treatment of autoimmune diseases, including Type 1 diabetes and rheumatoid arthritis (the “personalized immune” mouse); studies of lymphocyte turnover, chimerism and T cell trafficking in patients receiving intestinal and liver transplants; tracking of alloreactive T cells in human transplant recipients; and both pre-clinical and clinical studies of non-myeloablative hematopoietic cell transplantation for the induction of allograft tolerance.

Academic Appointments

  • Professor of Microbiology and Immunology and Surgical Sciences (in Surgery)
  • Michael J. Friedlander Professor of Medicine

Administrative Titles

  • Director, Columbia Center for Translational Immunology
  • Director of Research, Transplant Initiative
  • Director, Bone Marrow Transplantation Research, Division of Hematology/Oncology

Languages

  • French

Gender

  • Female

Credentials & Experience

Education & Training

  • MD, 1982 Medicine, University of Toronto
  • Internship: 1983 Montreal General Hospital
  • Internship: 1985 McGill University
  • Residency: 1985 University of Toronto

Committees, Societies, Councils

American College of Physicians, Associate, 1985-1988

College of Physicians and Surgeons of Ontario, Member, 1985-

American Association of Immunologists, Member, 1989-

The Transplantation Society, Member, 1990-

International Society for Experimental Hematology, Member, 1991-

American Society of Hematology, Member, 1992-

American Society for Blood and Marrow Transplantation, Member, 1994-

American Society of Transplantation, Member, 1996-

Councilor, International Xenotransplantation Association, 1998-2001

American Diabetes Association, Member, 1999-

Councilor, The Transplantation Society, 2000-2006

Councilor, International Xenotransplantation Association, 2001-2005

President, International Xenotransplantation Association, 2005-2007

Vice President, The Transplantation Society, 2006-2010

Councilor, Interurban Clinical Club, 2007-2010

Councilor, The Transplantation Society, 2013-2016

New York Academy of Science, Member, 2014-2015

Committees

National Institute of Allergy and Infectious Diseases Advisory Council, 2005-2009

AAI Nominating Committee, 2005-2006

NHLBI Strategic Planning (Cellular Therapeutics), 2006

AAI Block Co-Chair, Transplantation Immunology, 2006

Advisory Board of the Lawrence Transplant Foundation, 2006

The Transplantation Society Communications Committee, 2006-

Representative for The Transplantation Society to Federation of Clinical Immunology Societies Steering Committee, 2006-2008

Member, Xenotransplant Program Subcommittee for the 2008 Congress of the Transplantation Society, 2006-2008

Member, International Advisory Committee for the 2008 Congress of the Transplantation Society, 2006-2008

The Transplantation Society Ethics Committee, 2006-2010

NIAID T32, Interdisciplinary Training in Transplantation Biology, University of Pittsburgh, Scientific Advisory Board, 2007-

Member, Scientific and Medical Research Funding Working Group, California Institute for Regenerative Medicine, 2008-

Member, Ad hoc Planning and Evaluation Panel for Clinical Research Efforts Supported by the Special Funding Program for Type 1 Diabetes, NIDDK, 2008

Member, Advisory Board, Faculty of 1000 Biology, 2008-2010

Participant, First Global Consultation on Regulatory Requirements for Xenotransplantation, 2008

Clinical Trials, World Health Organization, Changsha, China, November 17-22, 2008

Leader, Task Force on Basic Science, The Transplantation Society, 2008-

FOCIS Nominating Committee, 2010

Ad Hoc Member, Cancer Immunopathology and Immunotherapy Study Section, NIH, 2010

Member, Scientific Council, Institut Hospitalo Universitaire, 2010

Member, Blood and Marrow Transplant Clinical Trials Network Review Panel, NIH, 2011

Member, Expert Panel for the Special Statutory Funding Program for Type 1 Diabetes Research, NIDDK, 2011

Ad Hoc Member, Board of Scientific Counselors, National Heart, Lung, and Blood Institute, NIH, 2011

Member, Scientific Advisory Board, Diabetes Research Institute, University of Miami Miller School of Medicine, 2011

Member, Steering Committee, Women in Transplantation Program, The Transplantation Society, 2011-

Women in Transplantation (WIT) Mentor (Nina Pilat-Michalek and Evelyn Salvaris), 2011-

Ad Hoc Member, Cancer Immunopathology and Immunotherapy Study Section, NIH, 2012

Member, Communications Committee, The Transplantation Society, 2012

Member, Special Emphasis Panel on Transplantation, Tolerance & Tumor Immunology, NIH, 2012

Chair, Research Using Subjects from TrialNet Living Biobank Review Panel, NIDDK, NIH, 2012

Member, DMICC Workshop on Research Supported by the Special Statutory Funding Program for Type 1 Diabetes Research, NIDDK, NIH, 2013

Ad Hoc Reviewer, Mentor-Based Postdoctoral Fellowship Awards, American Diabetes Association, 2013

At-Large Director, Board of Directors, Federation of Clinical Immunology Societies, 2013-

Member, Transplantation, Tolerance, and Tumor Immunology Study Section, Center for Scientific Review, NIH, 2013-2017

Co-Chair, Abstract Review Committee, World Transplant Congress Meeting, 2013-2014

Chair, Keynote Symposium, International Xenotransplantation Association Congress, Osaka, Japan, 2013

Ad Hoc Reviewer, Mentor-Based Postdoctoral Fellowship Awards, Roche Organ Transplantation Research Foundation (ROTRF), 2013

Member, Lupus Drug Repurposing Vetting Committee Meeting, Boston, MA, 2014

Ad Hoc Reviewer, Cancer Immunopathology and Immunotherapy Study Section (CII), NIH, 2014

Basic Science Co-Chair, Scientific Program Committee, 2016 International Congress of the Transplantation Society, 2014-2016

Selection Committee, Woman Leader in Transplantation Award, 2014

Chair, Institute of Medicine Interest Group 13 on Cancer, Stem Cell Biology and Transplantation, 2014-2016

Co-Chair, Journal Committee, 2016 International Congress of the Transplantation Society, 2014-

Expert Reviewer, Transplant Library (Centre for Evidence in Transplantation), 2014-

Award Selection Committee Member, Basic/Translational Science Award, The Transplantation Society, 2014

Abstract Reviewer, FOCIS 2015, 2014-

Children’s Cancer Research Institute, Vienna, Scientific Advisory Board member, 2014-

Co-Chair, Symposium 3, 37th Annual Meeting of the Japan Society for Hematopoietic Cell Transplantation, 2015

Co-Chair, Thematic Symposium, The Best of Transplantation, 2015, FOCIS, San Diego, 2015

Chair, Symposium: Immunosuppression & Tolerance, IPITA IXA CTS Joint Congress, Melbourne, Australia, 2015

Co-Chair, Abstract Driven Session: Tolerance & Zoonosis, IPITA IXA CTS Joint Congress, Melbourne, Australia, 2015

Labex IGO, Scientific Advisory Board, Nantes, France, 2014-

Chair of Session Immunologic Crossroads in Transplantation Tolerance: An Optimal and Feasible Solution, FOCIS Boston, MA, 2016

Scientific Advisory Board, NIH/NIAID Systems Biology of Antibacterial Resistance grant, UCLA, 2016

Chair of Post-Graduate Course on Computational Immunology, TTS Conference, Hong Kong, China, 2016

Plenary Chair: Basic and Translational Sciences, TTS Conference, Hong Kong, China, 2016

Starr Cancer Consortium: Scientific Advisory Board, New York, NY, 2014-

FOCIS Nominating Committee, Boston, MA, 2016-

Consultant, New Leaf Venture Partners, 2016

Consultant, Magenta Therapeutics, 2016

Congress Board Member, 2017 International Xenotransplantation Association Congress, Maryland, 2017

Consultant, Recombinetics, 2017

Chair, Human Immunity to Islets, HIRN 2017 Annual Investigator Meeting, 2017

Consultant, Flagship Pioneering, 2017

Consultant, Bayer Healthcare, 2017

Consultant, Ossium Health Corporation, 2017

Consultant, Editas Medicine, 2017

FOCIS 2017 Session Chair, Thematic Symposia, Alarmins as Immune Targets, Session Chair Oral Abstract Sessions, The Forefront of Immune Regulation 2017

Member, Scientific Program Committee, 2018 International Congress of The Transplantation Society, 2018

Expert Member, International Scientific Advisory Committee (ISAC) of the One-Transplant-for-LifeNetwork, 2018

Member, Ad Hoc Evaluation Committee for Tenure at Harvard Medical School, 2018

Panel Member, Recent Advances and Opportunities in the Development and Use of Humanized Immune System Mouse Models Meeting, NIAID, 2018

Representative for The Transplantation Society on the 2019 International Xenotransplantation Association Congress Board, 2018-2019

Member, The Transplantation Society 2020 Scientific Program Committee, 2018-2020

Consulting, Regeneron Pharmaceuticals, Inc., 2019

Chair, Labex Immunology Graft Oncology Scientific Advisory Board, 2020-2025

Honors & Awards

1991 American Cancer Society Junior Faculty Research Award
1998 Wyeth-Ayerst Young Investigator Award, American Society of Transplant Physicians
1999 Honorary Master of Arts Degree, Harvard Medical School
2002 Moses Baron Lecture, University of Minnesota, MN
2005 Elected to membership, Interurban Clinical Club
2007 American Society of Transplantation (AST) Basic Science Established Investigator Award
2007 Honorary Professorship, Wenzhou Medical College
2009 Distinguished Lecturer, American Association of Immunologists Annual Meeting
2009 Fellow, AAAS (American Association for the Advancement of Science)
2009 Martin Research Prize for Excellence in Clinical Research, MGH
2009 Erwin Neter Memorial Lecture, Association of Medical Laboratory Immunologists
2009 8th Annual Catherine Tuck, MD Memorial Lecture
2009 Elected to membership, Institute of Medicine of the National Academies
2010 Elected to membership, Association of American Physicians
2010 TTS Roche Award for Outstanding Achievement in Transplantation Science (Basic)
2012 Pixie Campbell Memorial Lecture, 13th Annual Colorado Immunology Conference
2014 Award for Outstanding Achievement in Transplantation (Basic Science), The Transplantation Society
2015 Dean’s Distinguished Lecture in the Clinical Sciences, Dean’s Distinguished Lecture Series of the College of Physicians and Surgeons, Columbia University Medical Center
2016 Elected to membership The Practitioners Society, New York
2017 Elected to Honorary Membership, International Xenotransplantation Association
2017 Keynote Speaker, 8th Annual Retreat, Human and Translational Immunology Program, Yale University, New Haven, Connecticut
2017 Irene and Arthur Fishberg Prize for Significant Original Contributions to Internal Medicine
2017 Honorary Member Lecture, International Xenotransplantation Association, Baltimore, Maryland
2017 Charles G. Orosz Lecture, 18th Annual Great Lakes Transplant Immunology Forum, Madison, Wisconsin
2018 26th Annual Meeting of the Japanese Society for Histocompatibility and Immunogenetics, Special Lecture, Hiroshima, Japan
2018 The CIS Rose/Fahey Founders Lecture, the Clinical Immunology Society Annual Meeting, Toronto, Canada
2018 Keynote Lecture, Harnessing Immune Metabolism to Treat Cancer and Other Diseases Symposium, Ann Arbor, Michigan
2018 Keynote Lecture, 18th Annual Meeting of the Federation of Clinical Immunology Societies, San Francisco, California
2018 The Medawar Prize for the Most Outstanding Contributions in the Field of Transplantation
2018 The Leslie Brent Award for the Best Basic Science Paper, “Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques” Published in Transplantation
2018 The 13th Annual Oscar Salvatierra Jr. Lectureship, Palo Alto, California
2019 The Stevens Triennial Prize for Original Medical Research that is Most Meritorious
2019 American Society of Transplantation/Astellas Research Grant Award

Research

Our research is in the areas of hematopoietic cell transplantation, achievement of graft-versus-leukemia effects without GVHD, organ allograft tolerance induction, autoimmune disease and xenotransplantation.

Our research has developed ways to utilize bone marrow transplantation as immunotherapy to achieve graft-versus-tumor effects while avoiding the common complication of such transplants, graft-versus-host disease. Another major area has been to utilize bone marrow transplantation for the induction of transplantation tolerance, both to organs from the same species (allografts) and from other species (xenografts). Our laboratory has worked toward the development of clinically feasible, non-toxic methods of re-educating the T cell, B cell and NK cell components of the immune system to accept allografts and xenografts without requiring long-term immunosuppressive therapy. We pioneered xenogeneic thymic transplantation as an approach to tolerance induction. We have demonstrated that non-myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes. We have recently developed novel humanized mouse models allowing "personalized" analysis of immune disease pathogenesis and immunotherapy. Additionally, we have developed novel tools for the analysis of the human alloresponse and are using these tools to better understand organ transplant immunobiology and tolerance in patients.

Research Interests

  • High Dimensional Immune Profiling in Transplantation
  • Human Immune Repertoire Alloreactivity
  • Transplantation tolerance
  • Type 1 diabetes autoimmunity
  • Xenotransplantation

Grants

Past

American Cancer Society, Principal Investigator, 1991

Achieving the Graft-vs-Leukemia Effect Without GVHD (declined)

NIH/NCI, Principal Investigator, Achieving the Graft-vs-Leukemia Effect Without GVHD, 1991-1994

NIAID, Principal Investigator, A New Approach to Preventing GVHD, 1991-1995

NIH/NCI, R01, Co-Investigator, IL-2 in HLA Mismatched Bone Marrow Transplantation, 1994-1996

NHLBI, Co-Investigator, Retroviral Transduction of a Class I MHC Gene, 1993-1997

NIH/NCI, R01, Principal Investigator, T Cell Activities Promoting GVL, GVHD and Alloengraftment, 1994-1998

American Cancer Society, Principal Investigator, Achieving Graft-vs-Leukemia Effects without Graft-vs-Host Disease, 1995-1998

Sponsored Research Agreement, BioTransplant, Inc., Co-Investigator, Xenograft Research in Miniature Swine, 1991-1999

Sponsored Research Agreement, Bio Transplant, Inc., Role of Chemokines in GVHD Pathogenesis, 2001-2002

Sponsored Research Agreement, Bio Transplant, Inc., Avoiding Irradiation in Mixed Chimeras, 2001-2002

Sponsored Research Agreement, Bio Transplant, Inc., Pig Cytokines for Enhancement of Chimerism and Tolerance in a Mouse Model, 2001-2002

NIH/NHLBI, P01, Project Leader, Component Project 4: Xenogeneic Tolerance in Mice, 1998-2003

Tolerance: An Approach to Cardiac Allo- and Xenotransplants

Juvenile Diabetes Foundation, Principal Investigator, Project #10: Mixed Bone Marrow, 1998-2003

Chimerism as a Treatment for Diabetes, JDF Center for Islet Transplantation at HMS

NIH/NIAID, R01, Principal Investigator, T and B Cell Tolerance in Human Mixed Chimeras, 1999-2003

NIH/NCI, R01, Co-Investigator, Mixed Chimerism Following BMT for Hematologic Malignancy, 2000-2003

NIH/NHLBI, R01, Principal Investigator, Compatibility of Swine Stem Cells and Human Stroma, 1996-2004

NIH/NCDDG-HIV, P01, Principal Investigator (Program Director), Program Project Grant, 1996-2005

Xenogeneic Stem Cell and Thymic Replacement in AIDS

NIAID/NIDDK/JDRF Immune Tolerance Network, Subcontract Principal Investigator, 2001-2006

Combined HLA-Matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure

NIAID Bioinformatics Integration Support Contract (BISC) System Scientific Advisory Board, 2003-2007

Multiple Myeloma Research Foundation: Immunobiology of Donor Lymphocyte infusions (DLI), 2004-2005

to separate GVHD and GVT effects

Multiple Myeloma Research Foundation; Principal Investigator, Immunobiology of Lymphohematopoietic GVH Reactions, 2006-2007

Lymphohematopoietic GVH Reactions.

JDRF, Program Project Grant, JDRF Center on Immunological Tolerance in Type 1 Diabetes. 2003-2007

Project Leader, Project #5: Mixed Chimerism in Diabetic NOD Mice

NIH/NIAID R01 Principal Investigator, T and B Cell Tolerance via Marrow Transplantation, 2003-2008

(declined because project was funded under PO1 # HL18646-26)

NIH/NHLBI, P01 Tolerance: An approach to Cardiac Allo and Xenotransplantation, 2003-2008

Project Leader, Project #3 T & B cell tolerance in presensitized mice

NIH/NCI, R01, Principal Investigator, Separation of GVH and GVL in Mouse Models,1999-2009

Multiple Myeloma Research Foundation, Senior Research Award, Stem Cell Rejection to Induce Anti-tumor Immunity, 2007-2009

NIH/NIAID, P01, Thymic Xenotransplantation for Immune Restoration, 2005-2010

Project Leader, Project 3: Porcine Thymic Transplantation to Mice with Human Immune Systems

JDRF, Basic Science Grant, Principal Investigator, Tolerance Induction by Xenogeneic Thymic Transplantation, 2007-2010

NIH/NIAID, R21, Principal Investigator, In Vivo Delivery of siRNAs as a Novel Approach to Inducing Mixed Chimerism, 2009-2011

NIH/NHLBI, R01, Principal Investigator, Mixed Chimerism as an Approach to Transplant Tolerance, 1993-2011

NIH/NCI, P01, Principal Investigator (Program Director) GVL without GVHD across HLA Barriers: Translational Studies. 2006-2011

NIH/NCI, R01, Principal Investigator, Control of CD4 and CD8-mediated GVHR, 2006-2011

(declined because project was funded under PO1#CA 111519-01A2)

ROTRF, Principal Investigator, Achieving durable mixed chimerism using regulatory cells in non-human primates, 2001-2012

JDRF, Program Project Grant, JDRF Center on Immunological Tolerance in Type 1 Diabetes, 2008-2012

Project Leader, Project #3: Regulation and homeostasis of diabetic human T cells

NIH/Immune Tolerance Network, Co-Principal Investigator, Renal Allograft Tolerance through Mixed Chimerism, 2008-2014

NIH/NIAID, R01, Principal Investigator, Mechanisms of tolerance in recipients of combined kidney and, 2009-2012

bone marrow transplants

NIH/NHLBI/ARRA, Co-Investigator, Immune response to allogeneic hESC-derived endothelial cells in hu-mice. 2010-2012

NIH/NIAID R01, Principal Investigator, Antibody Tolerance by Mixed Chimerism Induction, 2009-2014

(declined because project was funded under PO1#HL18646)

Helmsley Foundation, Co-Investigator, Generation of Thymic Epithelial Cells from Human Pluripotent Stem Cells, 2014-2015

Frederick Banting Foundation, Principal Investigator, Durable Mixed Chimerism for Islet Allograft Tolerance, 2013-2015

ROTRF, Principal Investigator, A blood biomarker of kidney transplant outcomes: tracking and donor-reactive T cells, 2014-2015

NIH/NIDDK, R01, Co-Investigator, Contribution of B cells to Human Cardiac Allograft Vasculopathy, 2015-2016

NIH/ITN, Principal Investigator, Tracking T regulatory cells in ITN036 CKBMT patients, 2014-2016

NIH/NAIMS, R21, Co-Investigator, An RA immune system derived from patient’s stem cells, 2013-2016

NIH/NIAID, R01, Principal Investigator, Pig to human thymic xenotransplantation, 2010-2016

NIH/NIAMS P30, Co-Investigator, Columbia University Medical Center Skin Disease, 2010-2016

Research Center; Flow Cytometry Core

DoD, CDMRP, Principal Investigator, Reconstructive Transplantation Research Award, 2015-2017

Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP

Cell Co-Infusion

NIH/NIAID, P01, Principal Investigator (Contact PI), A Tolerance Approach to, 2001-2017

Xenotransplantation; Proj 3: Tolerance of Adaptive and Innate Human Anti-Pig Immune

Responses in Humanized Mice

NIH/NIDDK, P30, Core Leader, Diabetes & Endocrinology Research Center, Flow Cytometry Core, 2014-2018

Stemnion, Principal Investigator, Facilitating mixed allogeneic chimerism induction by, 2015-2017

co-transplantation of Amnion-derived Multipotent Progenitor Cells (AMP cells) in

humanized mice with established immune system

NIH/NIAID, R56, Principal Investigator, Immune response to combined liver and bone marrow, 2016-2017

transplant for tolerance in NHP

CELLDEX Therapeutics, Principal Investigator, Combined use of FLt3L and rapamycin to promote, 2016-2018

durable mixed allogeneic chimerism in NHP

NIH/NIAID, U01, Co-Investigator Effects of inhibiting early inflammation in kidney, 2016-2017

transplant patients

NIH/NIAID, R56, Co-Investigator, Tolerance to Vascularized Allografts in Miniswine, 2017-2018

JDRF, SRA, Co Investigator, Improving engraftment and survival of pig islet xenografts, 2017

through transgenic expression of human CD47

ITB-MED, Sponsored Research Project, Principal Investigator, Effect of Siplizumab, 2017

on natural Tregs and effector T cells

NIH/NIAID, RO1, Principal Investigator, Tolerance of Adaptive and Innate Human Anti-pig, 2017-2022

Immune Responses in Humanized Mice (declined because project was funded under PO1 “Tolerance of Adaptive and Innate Human Anti-pig Human Anti-Pig Immune Responses in Humanized Mice”)

Present

NIH/NIDDK, P30, Core Leader, Diabetes & Endocrinology Research Center, Flow Cytometry Core, 2014-2018

NIH/NIAID, P01, Principal Investigator (Contact PI), A Tolerance Approach to Xenotransplantation; 2001-2017

Proj 3: Tolerance of Adaptive and Innate Human Anti-Pig Immune Responses in Humanized Mice

NIH/NIAID, P01, Project Leader, Tissue compartmentalization of human lymphocytes; 2013-2018

Proj 4: Lymphocyte reconstitution and responses in intestinal transplantation

NIH/NHLBI, P01, Co-Investigator, New Approaches to Cardiothoracic Tolerance Induction, 2009-2019

NIH/NIDDK, UC4, Principal Investigator, Mice with Autologous Human T1d-derived Immune, 2014-2019

Systems and iPSC-derived Beta Cells

Stemnion, Principal Investigator, Facilitating mixed allogeneic chimerism induction by, 2015-2017

co-transplantation of Amnion-derived Multipotent Progenitor Cells (AMP cells) in humanized mice with established immune system

DoD, CDMRP, Principal Investigator, Reconstructive Transplantation Research Award, 2015-2017

Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-Infusion

NIH/OD R01, Principal Investigator, Robust allograft tolerance in non-human primates, 2015-2020

NIH/NIDDK, R01, Principal Investigator, Immune Response to iPSC-derived Beta Cells in Type 1 Diabetes, 2015-2019

United Therapeutics/Lung Biotechnology, Principal Investigator, Collaboration on Xenograft lung Tolerance, 2015-2018

NIH/NIAID, R56, Principal Investigator, Immune response to combined liver and bone marrow, 2016-2017

transplant for tolerance in NHP

CELLDEX Therapeutics, Principal Investigator, Combined use of FLt3L and rapamycin to promote, 2016-2018

durable mixed allogeneic chimerism in NHP

NIH/NIAID, U01, Co-Investigator Effects of inhibiting early inflammation in kidney transplant patients, 2016-2017

NIH/NIAID, R56, Co-Investigator, Tolerance to Vascularized Allografts in Miniswine, 2017-2018

JDRF, SRA, Co Investigator, Improving engraftment and survival of pig islet xenografts, 2017

through transgenic expression of human CD47

ITB-MED, Sponsored Research Project, Principal Investigator, Effect of Siplizumab, 2017

on natural Tregs and effector T cells

NIH-NIAID, U19, Principal Investigator, Regulatory T cells to promote mixed chimerism for, 2017-2022

tolerance to islets and kidneys from deceased and living donors

NIH/NIAID, PO1, Contact Principal Investigator, Project Leader, Tolerance of Adaptive and Innate, 2017-2021

Human Anti-Pig Immune Responses in Humanized Mice

NIH/NHLBI, P01, Co-Investigator, New Approaches to Cardiothoracic Tolerance Induction, 2014-2019

NIH/NIDDK, UC4, Principal Investigator, Mice with Autologous Human T1D-derived Immune, 2014-2019

Systems and iPSC-derived Beta Cells

NIH/OD R01, Principal Investigator, Robust allograft tolerance in non-human primates, 2015-2020

NIH/NIDDK, R01, Principal Investigator, Immune Response to iPSC-derived Beta Cells in, 2015-2019

Type 1 Diabetes

United Therapeutics/Lung Biotechnology, Sponsored Research Project, Principal Investigator, 2015-2019

Collaboration on Xenograft Lung Tolerance

NIH-NIAID, U19, Principal Investigator, Regulatory T cells to promote mixed chimerism for, 2017-2022

tolerance to islets and kidneys from deceased and living donors

NIH/NIAID, PO1, Contact Principal Investigator, Project Leader, Tolerance of Adaptive and Innate, 2017-2021

Human Anti-Pig Immune Responses in Humanized Mice

NIH/NCATS, R21, Principal Investigator, TCR and BCR deep sequencing to distinguish, 2018-2020

autoimmune recurrence from allograft rejection

American Society of Transplantation, Astellas Research Grant, Primary Investigator, A specific, 2018-2020

Biomarker for the host anti-donor T cell response

NIH/NIAID, R01, Multiple Principle Investigator, Intestinal Allograft Tolerance in Large, 2018-2023

Animals

NIH/NIAID, P01, Project Leader, Tissue compartmentalization of human lymphocytes; 2018-2023

Project 3: Lymphocyte reconstitution and responses in intestinal transplantation

NIH/NIAID, R21, Principle Investigator, Thymic negative selection in human T1D immune systems, 2019-2021

Selected Publications

  • Luchsinger LL, Strikoudis A, Danzl NM, Bush EC, Finlayson MO, Satwani P, Sykes M, Yazawa M, Snoeck HW. Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro. Cell Stem Cell. 2019 May 31. pii: S1934-5909(19)30206-1. doi: 10.1016/j.stem.2019.05.002. PMID: 31178255 [Epub ahead of print]
  • Hawthorne WJ, Cowan PJ, Bühler LH, Yi S, Bottino R, Pierson RN 3rd, Ahn C, Azimzadeh A, Cozzi E, Gianello P, Lakey JRT, Luo M, Miyagawa S, Mohiuddin MM, Park CG, Schuurman HJ, Scobie L, Sykes M, Tector J, Tönjes RR, Wolf E, Nuñez JR, Wang W. Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, Changsha, Hunan, China December 12-14, 2018: "The 2018 Changsha Communiqué" The 10-Year Anniversary of The International Consultation on Xenotransplantation. Xenotransplantation. 2019 Mar;26(2):e12513. doi: 10.1111/xen.12513. PMID: 30980428
  • Khosravi-Maharlooei M, Obradovic A, Misra A, Motwani K, Holzl M, Seay HR, DeWolf S, Nauman G, Danzl N, Li H, Ho SH, Winchester R, Shen Y, Brusko TM, Sykes M. Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire. J Clin Invest. 2019 Mar 28;130:2446-2462. doi: 10.1172/JCI124358. PMCID: PMC6546456. [Commentary provided by Antonio La Cava, MD, PhD: La Cava A. Human T cell repertoire: what happens in thymus does not stay in thymus. J Clin Invest. 2019;129(6):2195-2197. https://doi.org/10.1172/JCI128371. PMCID: PMC6546474.]
  • Snyder ME, Finlayson MO, Connors TJ, Dogra P, Senda T, Bush E, Carpenter D, Marboe C, Benvenuto L, Shah L, Robbins H, Hook JL, Sykes M, D'Ovidio F, Bacchetta M, Sonett JR, Lederer DJ, Arcasoy S, Sims PA, Farber DL. Generation and persistence of human tissue-resident memory T cells in lung transplantation. Sci Immunol. 2019 Mar 8;4(33). pii: eaav5581. doi: 10.1126/sciimmunol.aav5581. PMCID: PMC6435356.
  • Alonso-Guallart P, Zitsman J, Stern J, Kofmans B, Woodland D, Ho SH, Sondermeijer H, Buhler L, Griesemer A, Sykes M, Duran-Struuck R. Characterization, biology, and expansion of regulatory T cells in the Cynomolgus macaque for pre-clinical studies. Am J Transplant. 2019 Feb 15. doi: 10.1111/ajt.15313. PMID: 30768842 [Epub ahead of print]
  • Yoshihara S, Li Y, Danzl N, Sykes M, Yang YG. Posttransplant hemophagocytic lymphohistiocytosis driven by myeloid cytokinds and vicious cycles of T-cell and macrophage activation in humanized mice. Front Immunol. 2019 Feb 13;10:186. doi: 10.3389/fimmu.2019.00186. PMCID: PMC6381030.
  • Spitzer T, Tolkoff-Rubin N, Cosimi B, McAfee S, Dey B, Chen YB, Delmonico F, Sykes M, Sachs DH, Kawai T. Twenty Year Follow Up of Histocompatibility Leukocyte Antigen-Matched Kidney and Bone Marrow Co-Transplantation for Multiple Myeloma with End Stage Renal Disease: Lessons Learned. Transplantation. 2019 Feb 12. doi: 10.1097/TP.0000000000002669. PMID: 30801529 [Epub ahead of print]
  • Fu J, Zuber J, Martinez M, Shonts B, Obradovic A, Wang H, Lau SP, Xia A, Waffarn EE, Frangaj K, Savage TM, Simpson MT, Yang S, Guo XV, Miron M, Senda T, Rogers K, Rahman A, Ho SH, Shen Y, Farber D, Griesemer A, Kato T, Sykes M. Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that are Maintained by a Circulating Pool. Cell Stem Cell. 2018 Nov 21. pii: S1934-5909(18)30543-5. doi: 10.1016/j.stem.2018.11.007. PMCID: PMC6398344. [Commentary provided by Norma Sue Kenyon, PhD: Kenyon NS. We Could Use More Tolerance: Role of Intestinal-Allograft-Derived Human Stem Cells. Cell Stem Cell. 2019 Feb 7;24(2):197-198. doi: 10.1016/j.stem.2019.01.009. PMID: 30735643]
  • Savage TM, Shonts BA, Obradovic A, DeWolf S, Lau S, Zuber J, Simpson MT, Berglund E, Fu J, Yang S, Ho SH, Tang Q, Turka LA, Shen Y, Sykes M. Early expansion of donor-specific Tregs in tolerant kidney transplant recipients. JCI Insight. 2018 Nov 15;3(22). pii: 124086. doi: 10.1172/jci.insight.124086. PMCID: PMC6302945
  • DeWolf S, Grinshpun B, Savage T, Lau SP, Obradovic A, Shonts B, Yang S, Morris H, Zuber J, Winchester R, Sykes M, Shen Y. Quantifying size and diversity of the human T cell. JCI Insight. 2018 Aug 9;3(15). doi: 10.1172/jci.insight.121256. PMCID: PMC6129121.
  • Sykes M. IXA Honorary Member Lecture, 2017: The Long and Winding Road to Tolerance. Xenotransplantation. 2018 May;25(3):e12419. doi: 10.1111/xen.12419. PMCID: PMC6011233.
  • Proto JD, Doran AC, Subramanian M, Wang H, Zhang M, Sozen E, Rymond CC, Kuriakose G, D'Agati V, Winchester R, Sykes M, Yang YG, Tabas I. Hypercholesterolemia induces T cell expansion in humanized immune mice. J Clin Invest. 2018 Jun 1;128(6):2370-2375. doi: 10.1172/JCI97785. PMCID: PMC5983331.
  • Sykes M. Immune monitoring of transplant patients in transient mixed chimerism tolerance trials. Hum Immunol. 2018 May;79(5):334-342. doi: 10.1016/j.humimm.2017.12.011. PMCID: PMC5924718.
  • Watanabe H, Sahara H, Nomura S, Tanabe T, Ekanayake-Alper DK, Boyd LK, Louras NJ, Asfour A, Danton MA, Ho SH, Arn JS, Hawley RJ, Shimizu A, Nagayasu T, Ayares D, Lorber MI, Sykes M, Sachs DH, Yamada K. GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels. Xenotransplantation. 2018 Sep;25(5):e12391. doi: 10.1111/xen.12391. PMCID: PMC6135720.
  • Fuchs A, GliwiÅ„ski M, Grageda N, Spiering R, Abbas AK, Appel S, Bacchetta R, Battaglia M, Berglund D, Blazar B, Bluestone JA, Bornhäuser M, ten Brinke A, Brusko TM, Cools N, Cuturi MC, Geissler E, Giannoukakis N, GoÅ‚ab K, Hafler DA, van Ham SM, Hester J, Hippen K, Di Ianni M, Ilic N, Isaacs J, Issa F, Iwaszkiewicz-GrzeÅ› D, Jaeckel E, Joosten I, Klatzmann D, Koenen H, van Kooten C, Korsgren O, Kretschmer K, Levings M, Marek-Trzonkowska NM, Martinez-Llordella M, Miljkovic D, Mills KH, Miranda JP, Piccirillo CA, Putnam AL, Ritter T, Roncarolo MG, Sakaguchi S, Sánchez-Ramón S, Sawitzki B, Sofronic-Milosavljevic L, Sykes M, Tang Q, Vives-Pi M, Waldmann H, Witkowski P, Wood KJ, Gregori S, Hilkens CMU, Lombardi G, Lord P, Martinez-Caceres EM and Trzonkowski P. Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization. Front. Immunol. 2018 Jan 15;(8):1844. doi: 10.3389/fimmu.2017.01844. PMCID: PMC5775516.
  • Borsotti C, Danzl NM, Nauman G, Hölzl MA, French C, Chavez E, Khosravi-Mararlooei M, Glauzy S, Delmotte FR, Meffre E, Savage DG, Campbell SR, Goland R, Greenberg E, Bi J, Satwani P, Yang S, Bathon J, Winchester R, Sykes M. HSC-extrinsic sex- and intrinsic autoimmune disease-related human B cell variation is recapitulated in humanized mice. Blood Advances. 2017 1:2007-2018; doi: 10.1182/bloodadvances.2017006932. PMCID: PMC5728279.
  • Kato Y, Griesemer AD, Wu A, Sondermeijer HP, Weiner JI, Duran-Struuck R, Martinez M, Slate AR, Romanov A, Lefkowitch JH, Sykes M, Kato T. Novel H-shunt Venovenous Bypass for Liver Transplantation in Cynomolgus Macaques. Comp. Med. 2017 Oct. In Press.
  • Tan S, Li Y, Xia J, Jin CH, Hu Z, Duinkerken G, Li Y, Khosravi Maharlooei M, Chavez E, Nauman G, Danzl N, Nakayama M, Roep BO, Sykes M, Yang YG. Type 1 diabetes induction in humanized mice. Proc Natl Acad Sci. 2017 Sep 5. pii: 201710415. doi: 10.1073/pnas.1710415114. [Epub ahead of print] PMID: 28874533
  • Yamada K, Sykes M, Sachs D. Tolerance in xenotransplantation. Curr Opin Organ Tran. 2017. In Press
  • Tan, S., Xia, J., Hu, Z., Li, Y., Duinkerken, G., Jin, CH., Li, Y., Danzl, N., Nakayama, M., Roep, B., Sykes, M., Yang, YY. Human CD4 cells engineered to express a patient-derived islet autoreactive T-cell receptor cause type 1 diabetes in humanized mice. Proc Nat Acad Sci. 2017. In Press.
  • Sui L, Chen X, Leibel R, Sykes M, Egli D. Beta cell replacement in mice using human type 1 diabetes nuclear transfer embryonic stem cells. Diabetes. 2017. In Press
  • Zuber J, Sykes M. Mechanisms of Mixed Chimerism-Based Transplant Tolerance. Trends Immunol. 2017 Aug 18. pii: S1471-4906(17)30146-1. doi: 10.1016/j.it.2017.07.008. [Epub ahead of print] PMID: 28826941
  • DeWolf S, Sykes M. Alloimmune T cells in transplantation. J Clin Invest. 2017 Jun 30;127(7):2473-2481. doi: 10.1172/JCI90595. Epub 2017 Jun 19. PMCID: PMC5490749
  • Gao B, Gu Y, Rong C, Moore C, Porcheray F, Wong W, Preffer FI, Saidman SL, Fu Y, AB Cosimi B, Sachs DH, Kawai T, Sykes M, Zorn E. Dynamics of B cell recovery following kidney/bone marrow transplant recipients. Transplantation. 2017 Apr 19. doi: 10.1097/ TP.0000000000001789. [Epub ahead of print] PMID: 28422925
  • Sprangers B, DeWolf S, Savage TM, Morokata T, Obradovic A1, LoCascio SA, Shonts B1, Zuber J, Lau SP, Shah R, Morris H, Steshenko V, Zorn E, Preffer FI, Olek S, Dombkowski DM, Turka LA, Colvin R, Winchester R, Kawai T, Sykes M. Origin of enriched regulatory t cells in patients receiving combined kidney/bone marrow transplantation to induce transplantation tolerance. Am J Transplant. 2017 Mar 1. doi: 10.1111/ajt.14251. Epub 2017 Apr 10. PMID: 28251801
  • Weiner J, Zuber J, Shonts B, Yang S, Fu J, Martinez M, Farber D, Kato T, Sykes M. Long-term persistence of innate lymphoid cells in the gut after intestinal transplantation. Transplantation. 2016 Dec 8, DOI: 10.1097/TP.0000000000001593. [Epub ahead of print] PMCID: PMC4228952
  • Duran-Struuck R, Buhler L, Alonso-Guallart P, Zitsman J, Kato Y, Wu A, McMurchy A, Woodland D, Griesemer A, Martinez M, Boskovic S, Kawai T, Cosimi A, Wuu C, Slate A, Mapara M, Baker S, Tokarz R, D'Agati V, Hammer S, Pereira M, Lipkin W, Wekerle T, Levings M, Sykes M. Effect of ex vivo expanded recipient regulatory T cells on hematopoietic chimerism and kidney allograft tolerance across MHC barriers in cynomolgus macaques. Transplantation. 2017 Feb;101 (2):274-283, DOI: 10.1097/TP.0000000000001559. PMCID: PMC5263090
  • Zuber J, Shonts B, Lau S, Obradovic A, Fu J, Yang S, Lambert M, Coley S, Weiner J, Thome J, DeWolf J, Farber D, Shen Y, Caillat-Zucman S, Bhagat G, Griesemer A, Martinez M, Kato T, Sykes M. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Science Immunology 07 Oct 2016: Vol. 1, Issue 4 eaah3732, DOI: 10.1126/sciimmunol.aah3732 PMCID: PMC5323244
  • Li HW, Vishwasrao P, Holzl MA, Chen S, Choi G, Zhao G, Sykes M. Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model. Am J Transplant. 2017 Feb;17 (2):353-364. doi: 10.1111/ajt.13957. Doi: 10.11111/ajt. Epub 2016 Aug 10.PMC5414033
  • Xia J, Hu Z, Yoshihara S, Li Y, Jin CH, Tan S, Li W, Chen Q, Sykes M, Yang YG. Modeling Human Leukemia Immunotherapy in humanized mice. EBiomedicine 2016 Jun 23 pii: S2352-3954 (16)30285-7 Doi: 10.1016/j.ebiom.2016.06.028. PMCID: PMC5006579
  • Bartlett ST, Markmann JF, Johnson P, Korgren O, Hering BJ, Scharp D, Kay TW, Bromberg J, Odorico JS, Weir GC, Bridges N, Kandaswamy R, Stock P, Friend P, Gotoh M, Cooper DK, Park CG, O;Connell P, Stabler C, Matsumoto S, Ludwig B, Choudhary P, Kovatchev B, Rickels MR, Sykes M, Wood K, Kraemer K, Hwa A, Stanley E, Ricordi C, Zimmerman M, Greenstein J, Montanya E, Otokoski T. Report from IPITA-TTS Opinion Leaders Meeting on the Future of β-Cell Replacement. Transplantation. 2016Jul 100(7):e25-31. Doi: 10.1097 PMCID: PMC4741413
  • Hirata Y, Li HW, Takahashi K, Ishii H, Sykes M, Fujisaki J. MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice. PLoS One. 2015 Nov 6; 10(11):e0141785. Doi: 10.1371/journal.pone.014785, eCollection 2015. PMCID: PMC4636372
  • Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. American Journal of Transplantation. 2015 Nov; 15(11):2908-20. Doi: 10.1111/ajt.13480. Epub 2015 Oct 13. PMCID: PMC4725587
  • DeWolf S, Morris H, Shen Y, Sykes M. Author response to comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients". Science Translational Medicine. 2015 Jul 22; 7(297):297Ir1. Doi: 10.1126/scietranslmed.aac9461. PMCID: Not Applicable.
  • Li HW, Andreola G, Carlson AL, Shao S, Lin CP, Zhao G, Sykes M. Rapid Functional Decline of Activated and Memory Graft-versus-Host-Reactive T Cells Encountering Host Antigens in the Absence of Inflammation. Journal of Immunology. 2015 Aug 1; 195(3): 1282-92. Doi: 10.4049/jimmunol.1401511. Epub 2015 Jun 17. PMCID: PMC4506852.
  • Sykes M. Immune tolerance in recipients of combined haploidentical bone marrow and kidney transplantation. Bone Marrow Transplantation. 2015 Jun; 50 Supple 2:S82-6. Doi: 10.1038/bmt.2015.102. PMCID: PMC4968035
  • Weiner J, Duran-Struuck R, Zitsman J, Buhler L, Sondermeijer H, McMurchy A, Levings M, Sykes M, Griesemer A. Restimulation After Cryopreservation and Thawing Preserves the Phenotype and Function of Expanded Baboon Regulatory T Cells. Transplantation Direct. February 2015, Volume 1 - Issue 1, p. 1-7. doi: 10.1097/TXD.0000000000000511
  • Zuber J, Rosen S, Shonts B, Sprangers B, Savage T, Richman S, Yang S, Lau S, DeWolf S, Vlad G, Zorn E, Wong W, Emond J, Martinez M, Kato T, Sykes, M. Macrochimerism in intestinal transplantation: association with lower rejection rates and multivisceral transplants, without GVHD. American Journal of Transplantation. 2015 Oct 15(10):2691-703 doi: 10.1111/ajt. 13325. Epub 2015 May 18. PMCID: PMC4575629.
  • Buchan S, Manzo T, Flutter B, Rogel A, Edwards N, Zhang L, Sivakumaran S, Ghorashian S, Carpenter B, Bennett C, Freeman G, Sykes M, Croft M, Al-Shamkhani A, Chakraverty R. OX40- and CD27-mediated co-stimulation synergize with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence. Journal of Immunology. 2015 Jan 1: 194(1):125-33. Doi:10.4049/jimmunol. 1401644. PMCID: PMC4272895.
  • Sykes, M. Introduction of David H. Sachs, MD, Recipient of the 2014 Medawar Prize. Transplantation. 2015 Feb; 99(2): 253-4. Doi: 10.1097/TP.0000000000000594.
  • Morris H, De Wolf S, Robins H, Sprangers B, Locascio S, Shonts B, Kawai T, Wong W, Yang S, Zuber J, Shen Y, Sykes M. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. (Note: accompanied by FOCUS Article "I spy alloreactive T Cells" by Maria-Luisa Alegre.) Science Translational Medicine 7, 272ra10 (2015). PMCID: PMC4360892
  • Kawai T, Sachs DH, Sprangers B, Spitzer T, Saidman S, Zorn E, Tolkoff-Rubin N, Preffer F, Crisalli K, Gao B, Wong W, Morris H, LoCascio S, Sayre P, Shonts B, Williams W, Smith R, Colvin R, Sykes M, Cosimi A. Long-Term Results in Recipients of Combined HLA-Mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression. American Journal of Transplantation. 2014 July; 14(7); 1599-611. doi: 10.1111/ajt.12731. PMID: 24903438 PMCID: PMC4228952
  • Li H, Yang YG, Sykes M. Thymic education of human T cells and regulatory T cell development in humanized mice. In: Humanized Mice for HIV Research; Poluektova LY, Garcia-Martinez JV, Koyanagi Y, Manz MG, Tager AM (Ed.), New York, NY, Springer Science+Business Media; 2014; 10: 127-140
  • Kalscheuer H, Onoe T, Dahmani A, Holzl M, Yamada K, Sykes M. Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts. Journal of Immunology, 2014 Apr 1;192(7):3442-50. doi: 10.4049/jimmunol.1302886. PMID: 24591363. PMCID: PMC3983999
  • Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 25th Edition. (Eds), Goldman L, Ausiello, D. Philadelphia, PA; Saunders Elsevier; 2016. Vol. 1. Pp. 236-240
  • Sykes M. Transplantation: Moving to the Next Level. Immunological Reviews; 2014. 2014 Mar;258(1):5-11. doi: 10.1111/imr.12161. PMID: 24517422. PMCID: PMC4038030.
  • Griesemer A, Yamada K, Sykes M. Xenotransplantation: Immunological hurdles and progress toward tolerance. Immunological Reviews; 2014 Mar;258(1):241-58. doi: 10.1111/imr.12152. PMID: 24517437. PMCID: PMC4023346
  • Haspot F, Li HW, Lucas CL, Fehr T, Beyaz S, Sykes M. Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells. American Journal of Transplantation, 2014 Jan 14(1): 49-58. doi: 10.1111/ajt.12525. PMID: 24304495. PMCID: PMC4045013
  • Sachs DH, Kawai T, Sykes M. Induction of Tolerance Through Mixed Chimerism. In: Turka L, Wood K, editors. Cold Spring Harbor Perspectives; 2013. 2014 Jan 1;4(1):a015529. doi: 10.1101/cshperspect.a015529.
  • Kawai T, Sachs DH, Sykes M, Cosimi AB, for the Immune Tolerance Network. HLA mismatched renal transplantation without maintenance immunosuppression-an update. Letter to the Editor. May 9, 2013 N Engl J Med 2013; 368:1850-1852. PMID: 23656665 PMC3760499
  • Sykes M, Wood K, Sachs DH. Transplantation Immunology. In: Paul WE, editor. Fundamental Immunology (7th edition). Philadelphia, PA: Lippincott Williams & Wilkins Publishers; 2013. 46: 1154-1199
  • Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 24th Edition. (Eds), Goldman L, Ausiello, D. Philadelphia, PA; Saunders Elsevier; 2012;48:235-239.
  • Li HW, Sachs J, Pichardo C, Bronson R, Zhao G, Sykes M. Nonalloreactive T cells prevent donor lymphocyte infusion-induced graft-versus-host disease by controlling microbial stimuli. J Immunol. 2012 Dec 15;189(12):5572-81. doi: 10.4049/jimmunol.1200045. Epub 2012 Nov 7. PubMed PMID: 23136200; PubMed Central PMCID: PMC3524834.
  • Wang H, Yang Y, Wang G, Wang S, Yeap BY, Sykes M, Yang YG. Donor bone marrow-derived T cells inhibit GVHD induced by donor lymphocyte infusion in established mixed allogeneic hematopoietic chimeras. PLoS One.2012;7(10):e47120.doi:10.1371/journal.pone.0047120. Epub 2012 Oct 15. PMCID:3471915.
  • Li H, Sykes M. Emerging concepts in haematopoietic cell transplantation. Nat Rev Immunol. 2012 May 25;12(6):403-16. doi: 10.1038/nri3226. PMID: 22627859 PMCID: PMC4006975
  • Kalscheuer H, Danzl N, Onoe T, Faust T, Winchester R, Goland R, Greenberg E, Spitzer TR, Savage DG, Tahara H, Choi G, Yang YG, Sykes M. A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med. 2012 Mar 14;4(125):125ra30. doi: 10.1126/scitranslmed.3003481. PubMed PMID: 22422991. NIHMS455065. PMCID: PMC3697150
  • Onoe T, Kalscheuer H, Danzl N, Chittenden M, Zhao G, Yang YG, Sykes M. Human natural regulatory T cell development, suppressive function and post-thymic maturation in a humanized mouse model. J Immunol. 2011 Oct 1;187(7):3895-903. Epub 2011 Aug 29. NIHMS 316848. PMCID: 3201793
  • Strober S, Spitzer TR, Lowsky R, Sykes M. Translational studies in hematopoietic cell transplantation: Treatment of hematologic malignancies as a stepping stone to tolerance induction. Semin Immunol. 2011 Aug;23(4):273-81. Epub 2011 Jun 25. PMCID: 3201788
  • Levesque V, Bardwell PD, Shimizu I, Haspot F., Benichou G, Yeap BY, Sykes M. B Cell-Dependent Memory T Cells Impede Nonmyeloablative Mixed Chimerism Induction in Presensitized Mice. AJT 2011. Am J Transplant. 2011 Nov;11(11):2322-31. doi: 10.1111/j.1600-6143.2011.03683.x. Epub 2011 Aug 10. PMCID: PMC3816363
  • Fujisaki J, Wu J, Carlson AL, Silberstein L, Putheti P, Larocca R, Gao W, Saito TI, Lo Celso C, Tsuyuzaki H, Sato T, Cote D, Sykes M, Strom TB, Scadden DT, Lin CP. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011 Jun 8;474(7350):216-9. doi: 10.1038/nature10160. PMCID 3725645
  • Lucas C, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DAA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood. 2011 May 19;117(20):5532-40 PMCID: 3109721
  • Farris AB, Taheri D, Kawai T, Fazlollahi L, Wong W, Tolkoff-Rubin N, Spitzer TR, Lafrate AJ, Preffer FI, LoCascio SA, Sprangers B, Saidman S, Smith RN, Cosimi AB, Sykes M, Sachs DH, Colvin RB. Acute renal endothelial injury during marrow recovery in a cohort of combined kidney and bone marrow allografts. Am J Transplant. 2011 Jun 10. doi: 10.1111/j.1600-6143.2011.03572 PMCID: 3128680
  • Andreola G, Chittenden M, Shaffer J, Cosimi A.B, Kawai T, Cotter P, LoCascio SA, Morokata T, Dey BR, Tolkoff-Rubin NT, Preffer F, Bonnefoix T, Kattleman K, Spitzer TR, Sachs DH, Sykes M. Mechanisms of Donor-Specific Tolerance in Recipients of Haploidentical Combined Bone Marrow/Kidney Transplantation. Am J Transplant. 2011 Jun;11(6):1236-1247. doi: 10.1111/j.1600-6143.2011.03566 PMCID: 3140222
  • Spitzer TR, Sykes M, Tolkoff-Rubin N, Kawai T, McAfee SL, Dey BR, Ballen K, Delmonico F, Saidman S, Sachs DA, Cosimi AB. Long Term Follow-Up of Recipients of Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma with End-Stage Renal Disease. Transplantation. 2011 Mar 27;91(6):672-6 PMCID: 3232059
  • LoCascio SA, Morokata T, Chittenden M, Preffer F, Dombrowski DM, Andreola G, Crisalli K, Kawai T, Saidman SL, Spitzer TR, Tolkoff-Rubin N, Cosimi AB, Sachs D, Sykes M. Mixed Chimerism, Lymphocyte Recovery and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving CKBMT to Induce Tolerance. Transplantation. 2010 Dec 27;90(12):1607-15. PMCID: 3059844
  • Griesemer A, Liang F, Hirakata A, Hirsh E, Lo D, Okumi M, Sykes M, Yamada K, Huang CA, Sachs DH. Occurrence of specific humoral non-responsiveness to swine antigens following administration of GalT-KO bone marrow to baboons. Xenotransplantation. 17 (4):300-312, 2010. PMCID: 2942069
  • Flutter B, Edwards N, Fallah-Arani F, Henderson S, Chai JG, Sivakumaran S, Ghorashian S, Bennett CL, Freeman GJ, Sykes M, Chakraverty R. Nonhematopoietic antigen blocks memory programming of alloreactive CD8+ T cells and drives their eventual exhaustion in mouse models of bone marrow. J Clin Invest. 2010 Nov 1;120(11):3855-68. doi: 10.1172/JCI41446. Epub 2010 Oct 18. PMCID: 2964967
  • Saito TI, Li H, Sykes M. Invariant natural killer T cells are required for antitumor responses induced by host-versus-graft responses. J. Immunol. 2010. Aug 15;185(4):2099-105. PMCID: 3111022
  • Saito TI, Fujisaki J, Carlson AL, Lin CP, Sykes M. Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells. Exp. Hematol. 2010, April;38(4):333-9.Epub 2010 Feb 16. PMC3965294
  • Onoe T, Kalscheuer H, Chittenden M, Zhao G, Yang YG, Sykes M. Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs. J Immunol. 2010 Jun 15;184(12):6756-65. PMCID: 3086709
  • Sykes M. Immune Evasion by Chimeric Trachea. New Engl. J. Med., 2010;362(2): 172-174. PMID: 20071709 PMCID N/A
  • Nikolic B, Onoe T, Takeuchi Y, Khalpey Z, Primo V, Leykin I, Smith RN and Sykes M. Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via non-myeloablative mixed chimerism induction in NOD mice. Transplantation, 2010; 89:23-32. PMCID: 3043373
  • Fehr T, Lucas C, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A and Sykes M. A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2010; 115: 1280-1287. PMCID: 2826238.
  • Mollov JL, Haspot F, Lucas C, Gaspar C, Guzman A and Sykes M. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T cell tolerance. Am J Transplant, 2010; 10(3): 518-526. PMID: 20121730 PMCID: PMC4215806.
  • Griesemer AD, Hirakata A, Shimizu A, Moran S, Tena A, Iwaki H, Ishikawa Y, Schule P, Arn JS, Robson SC, Fishman JA, Sykes M, Sachs DH, Yamada K. Results of gal-knockout porcine thymokidney xenografts. Am. J. Transplant. 2009; 9(12): 2669-2678. PMCID: 2801602
  • Cozzi E, Tallacchini M, Flanagan EB, Pierson RN, III, Sykes M and Vanderpool HY. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework. Xenotransplantation, 2009; 16: 203-214. PMID: 19799760 PMCID N/A
  • Porcheray F, Wong W, Saidman S, De Vito J, Girouard T, Chittenden M, Shaffer J, Tolkoff-Rubin N, Dey B, Spitzer T, Colvin R, Cosimi A, Kawai T, Sachs D, Sykes M and Zorn E. B cell immunity in the context of T cell tolerance after combined kidney and bone marrow transplantation in humans. Am. J. Transplant. 2009; 9: 2126-2135. PMCID:2837587
  • Habiro K, Sykes M, Yang YG. Induction of human T cell tolerance to pig xenoantigens via thymus transplantation in mice with an established human immune system. Am. J. Transplant. 2009; 9(6):1324-1329. PMCID: 2752337
  • Wang H, Asavaroengchai W, Wang MG, Wang S, Sykes M, Yang YG. Paradoxical effects of IFN-g in graft-vs.-host (GVH) disease reflect promotion of lymphohematopoietic GVH reactions and inhibition of epithelial tissue injury. Blood 2009; 113: 3612-19. PMCID: 2668848
  • Kurtz J, Raval F, Vallot C, Der J, Sykes M. CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance. Blood. 2009; 113: 3475 - 3484. PMCID: 2668856
  • Sachs DH, Sykes M, Yamada K. Achieving tolerance in pig-to-primate xenotransplantation: Reality or fantasy. Transplant. Int. 2009; 21(2):101-5. PMCID: 19059481
  • Sykes M. Mechanisms of Tolerance. In Thomas' Hematopoietic Cell Transplantation (4th Edition); Appelbaum FR, Forman SJ, Negrin RS and Blume KG (Eds.), Oxford, UK, Blackwell Publishing. 2009; 15: 188-207. PMCID: N/A
  • Fudaba Y, Onoe T, Chittenden M, Shimizu A, Shaffer J, Bronson R, Sykes M. Abnormal regulatory and effector T cell function predispose to autoimmunity following xenogeneic thymic transplantation. J. Immunol. 2008; 181: 7649 - 7659. PMCID: 2673578
  • Chakraverty R, Flutter B, Fallah-Arani F, Eom H-S, Means T, Andreola G, Schwarte S, Buchli J, Cotter P, Zhao G, Sykes M. The host environment regulates the function of CD8+ graft-versus-host-reactive effector cells J. Immunol. 2008; 181:6820-6828. PMCID: 18981100
  • Haspot F, Bardwell PD, Zhao G, Sykes M. High antigen levels do not preclude B cell tolerance induction to α1,3Gal via mixed chimerism. Xenotransplantation. 2008; 15:313-320. PMCID: 2633101
  • Fehr T, Wang S, Haspot F, Kurtz J, Blaha P, Hogan T, Chittenden M, Wekerle T, Sykes M. Rapid, deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: role of donor class II MHC and B cells. J Immunol. 2008; 181:4371-4380. PMCID: 2628539
  • Koporc Z, Pilat N, Nierlich P, Blaha P, Bigenzahn S, Pree I, Selzer E, Sykes M, Muehlbacher F and Wekerle T. Murine mobilized peripheral blood stem cells have a lower capacity than bone marrow to induce mixed chimerism tolerance. Am. J. Transplant. Am. J. Transplant. 2008; 8:2025-36. PMCID: 18828766
  • Shimizu I, Fudaba Y, Shimizu A, Yang Y-G, Sykes M. Comparison of human T cell repertoire generated in xenogenic porcine and human thymus grafts. Transplantation. 2008; 86: 601-610. PMCID: 26806891
  • Fehr T, Haspot F, Mollov J, Chittenden M, Hogan T, Sykes M. Alloreactive CD8 T cell tolerance requires recipient B cells, dendritic cells and MHC class II. J Immunol. 2008; 181: 165-173. PMCID: 18566381
  • Ting DT, Spitzer TR, Chaudhary A, Muzikansky A, Colby C, Power K, McAfee S, Ballen K, Attar E, Saidman SL, Preffer F, Sykes M, Dey BR. Clinical outcomes of late rather than early full-donor chimerism in patients with advanced lymphomas receiving nonmyeloablative allogeneic hematopoietic SCT. Bone Marrow Transplant. 2008; 42: 329-335. PMCID: 18587439
  • Haspot F, Fehr T, Gibbons G, Zhao G, Hogan T, Honjo T, Freeman GJ, Sykes M. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood. 2008; 112: 2149-55. PMCID: PMC2518911.
  • Sykes M, Wood K, Sachs DH. Transplantation Immunology. In: Fundamental Immunology (6th edition); Paul WE (Ed.), Philadelphia, PA, Lippincott Williams & Wilkins; 2008; 44: 1426-1489. PMCID: N/A
  • Tonomura N, Habiro K, Shimizu A, Sykes M, Yang Y-G. Antigen specific human T cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood. 2008 ; 111: 4293-4296. PMCID: 22887281
  • Gibbons C and Sykes M. Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed chimerism. Immunol. Rev. 2008; 223: 334-360. PMCID: 2680695
  • Sykes M, 2007 IXA Presidential Address. Progress toward an ideal source animal: opportunities and challenges in a changing world. Xenotransplantation. 2008; 15: 7-13. PMCID: 18333908
  • Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman S, Shaffer J, Preffer F, Ding R, Sharma V, Fishman J, Dey BR, Ko D, Hertl M, Goes N, Wong W, Williams W, Colvin RB, Sykes M, and Sachs DH. HLA-mismatched renal transplantation without maintenance immunosupression. New Engl. J. Med. 2008; 358(4): 353-361. PMCID: 18216355
  • Sykes M. Immune tolerance: mechanisms and application in clinical transplantation. J Intern Med. 2007; 262: 288-310.
  • Kawahara T, Rodriguez-Barbosa J-I, Zhao Y, Zhao G, Sykes M. Global unresponsiveness as a mechanism of natural killer cell tolerance in mixed xenogeneic chimeras. Am. J. Transplant. 2007; 7: 2090-2097.
  • Dey BR, Shaffer J, Yee AJ, McAfee S, Caron M, Power K, Ting DT, Colby C, Preffer F, Ballen K, Attar E, Saidman S, Tarbell N, Sachs DH, Sykes M, Spitzer TR. Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. Bone Marrow Transplant. 2007; 40(1):19-27.
  • Hongo D, Hadidi S, Damrauer S, Garrigue V, Kraft D, Sachs DH, Nikolic B and Sykes M. Porcine thymic grafts protect human thymocytes from HIV-1-induced destruction. J Infect Dis 2007; 196(6): 900-910.
  • Shaffer J, Villard J, Means TK, Dombkowski D, Dey BR, McAfee S, Ballen KK, Saidman S, Preffer FI, Sachs DH, Spitzer TR, and Sykes M. Regulatory T cell recovery in recipients of haploidentical non-myeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Exp. Hemat. 2007; 35(7): 1140-1152.
  • Pree I, Bigenzahn S, Fuchs D, Koporc Z, Nierlich P, Winkler C, Brandacher G, Sykes M, Muehlbacher F, Langer F, and Wekerle T. CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase. Transplantation 2007; 83:663-667.
  • Yamada K, Griesemer A, Sykes M and Sachs DH. Contransplantation of vasculariazed thymus and kidney from GalT-KO pigs to baboons. Xenotranplantation 2007; 14: 186-189.
  • Yang Y and Sykes M. Xenotransplantation - Current status and a perspective on the future. Nat. Rev. Immunol. 2007; 7(7):519-531.
  • Ide K, Wang H, Tahara H, Liu J, Wang X, Asahara T, Sykes M, Yang Y, Ohdan H. Role for CD47-SIRPα signaling in xenograft rejection by macrophages. Proc. Nat. Acad. Sci. USA 2007; 104(12):5062-5066.
  • Chakraverty R and Sykes M. The role of antigen-presenting cells in triggering GVHD and GVL. Blood. 2007; 110:-9-17. PMCID: 1896131
  • Koyama I, Nadazdin O, Boskovic S, Ochiai T, Smith RN, Sykes M, Sogawa H, Murakami T, Strom T, Colvin RB, Sachs DH, Benichou G, Cosimi AB, Kawai T. Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. Am. J. Transplant. 2007; 7(5):1055-1061.
  • Yang Y-G and Sykes M. Tolerance in xenotransplantation. Curr. Opin. in Organ Transplant. 2007;12: 169-175.
  • Asavaroengchai W, Wang H, Wang S, Wang L, Bronson R, Sykes M, Yang Y-G. An essential role for IFN-γ in regulation of alloreactive CD8 T cells following allogeneic heamatopoietic cell transplantation. Biol Blood Marrow Transplant. 2007; 13(1): 46-55.
  • Shimizu I, Kawahara T, Haspot F, Bardwell PD, Carroll MC, Sykes M. B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-αGal-producing B-1 cells. Blood. 2007: 109(4): 1773-1781.
  • Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang Y-G. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood. 2007; 109(2):836-842.
  • Sykes M. Transplantation Immunology. In: The Cecil Text Book of Medicine, 23rd Edition. (Eds), Goldman L, Ausiello, D; Saunders. New York, NY; Saunders Elsevier; 2007;46:277-282.
  • Sykes M, Cozzi E, d' Apice A, Pierson R, O'Connell P, Cowan P, Dorling A, Hering B, Leventhal J, Rees M, Sandrin M. Clinical trial of islet xenotransplantation in Mexico. Xenotransplantation. 2006;13(5):371-372 .
  • Chakraverty R, Cote D, Buchli J, Cotter P, Hsu R, Zhao G, Sachs T, Pitsilldes C, Bronson R, Means T, Lin C, Sykes M. An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J. Exp. Med. 2006;203(8):2021-2031.
  • Saito TI, Rubio MT, Sykes M. Clinical relevance of recipient leukocyte infusion as anti-tumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation. Exp. Hemat. 2006;34(9):1270-1276.
  • Sykes M and Cozzi E. Xenotransplantation of pig islets into Mexican children: Were the fundamental ethical requirements to proceed with such a study really met? Eur. J. Endocrinol. 2006;154(6):921-922.
  • Fudaba Y, Spitzer TR, Shaffer JM, Kawai T, Fehr T, Delmonico FL, Preffer FI, Tolkoff-Rubin, Dey BR, Saidman SL, Kraus A, Bonnefoix T, McAfee S, Power K, Kattelman K, Colvin RB, Sachs DH, Cosimi AB Sykes M. Myeloma responses and tolerance following combined kidney and non-myeloablative marrow transplantation in vivo and in vitro analyses. Am. J. Transplant. 2006;6:2121-2133.
  • Chakraverty R, Eom H-S, Sachs J, Buchli J, Cotter P, Hsu R, Zhao G, Sykes M. Host MHC Class II+ antigen-presenting cells and CD4 cells are required for CD8 mediated graft-versus-leukemia responses following delayed donor leukocyte infusions. Blood. 2006;108(6):2106-2113.
  • Rubio MT, Zhao G, Buchli J, Chittenden M, Sykes M. Role of indirect allo- and autoreactivity in anti-tumor responses induced by recipient leukocyte infusions (RLI) in mixed chimeras prepared with nonmyeloablative conditioning. Clin Immunol. 2006;120(1):33-44.
  • Ito H, Takeuchi Y, Shaffer JM, Sykes M. Anti-CD40L mAb can replace anti-CD4 mAb for the non-myeloablative induction of mixed xenogeneic chimerism. Transplantation 2006;82(2):251-257.
  • Mapara MY, Leng C, Kim YM, Bronson R, Lokshin A, Luster AD, Sykes M. Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR. Biol. Blood Marrow Transplant. 2006; 12(6):623-634.
  • Shimizu I, Smith RN, Zhao G, Medof E, Sykes M. Decay accelerating factor prevents acute humoral rejection induced by low levels of anti-αGal natural antibodies. Transplantation 2006;81(1):95-100.
  • Xu Y, Yang Y-G, Ohdan H, Ryan D, Harper D, Wu C, Kruger-Grey H, Thall A, Awwad M, Sykes M. Characterization of anti-gal antibody-producing cells of baboons and humans. Transplantation. 2006;81(6);940-948.
  • Fehr T, Bardwell PD, Sykes M. Use of skin grafting to demonstrate tolerance before kidney transplantation without immunosuppression in the recipient of a previous bone marrow transplant. Transplantation. 2005;80(9):1359-1360.
  • Bardwell PD, Ohdan H, Sykes M. B cell tolerance and xenotransplantation. Curr. Opin. in Organ Transplant. 2005;10(3)252-258.
  • Rubio MT, Means TK, Chakraverty R, Shaffer JM, Fudaba Y, Chittenden M, Luster AD, Sykes M. Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of Prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs. Int Immunol. 2005;17(12):1561-1572.
  • Fehr T, Takeuchi Y, Kurtz J, Wekerle T, Sykes M. Early regulation of CD8 T cell alloreactivity by CD4(+)CD25(- )T cells in recipients of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral deletion of donor-reactive CD8(+) T cells, precluding a role for sustained regulation. Eur. J. Immunol. 2005;35:(9)2679-2690.
  • Eom HS, Rubio MT, Means TK, Luster AD, Sykes M. T cell P/E-selectin ligand α(1,3)fucosylation is not required for GVHD induction. Exp. Hemat. 2005;33(12):1564-1573.
  • Kawahara T, Shimizu I, Ohdan H, Zhao G, Sykes M. Differing mechanisms of early and late B cell tolerance induced by mixed chimerism. Am. J. Transplant. 2005;5(12):2821-2829.
  • Sykes M, Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature 2005;435:620-627.
  • Rubio MT, Saito TI, Kattleman K, Zhao G, Buchli J, Sykes M. Mechanisms of the anti-tumor responses and host-versus graft reactions induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: a critical role for recipient CD4+ T cells and recipient leukocyte infusion-derived interferon-gamma-producing CD8+ T Cells. J. Immunol. 2005;175(2)665-676.
  • Dey BR, McAfee S, Colby C, Cieply K, Caron M, Saidman S, Preffer FI, Shaffer JM, Tarbell N, Sackstein R, Sachs DH, Sykes M, Spitzer TR. Anti-tumor response despite loss of donor chimerism in patients treated with nonmyeloablative conditioning and allogeneic stem cell transplantation. Br. J. of Hematol. 2005;128:351-359.
  • Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O'Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DKC, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH. Marked prolongation of porcine renal xenograft survival in baboons through the use of Gal-T knock out donors and the co-transplantation of vascularized thymic tissue. Nat. Med. 2005;11(1):32-34..
  • Sykes M, d'Apice A, Sandrin M. IXA Ethics Committee: Position paper of the Ethics Committee of the International Xenotransplantation Association. Transplantation 2004;78:1101-1107.
  • Kawai T, Sogawa H, Boskovic S, Abrahamian G, Smith R-N, Wee S-L, Andrews D, Nadazdin O, Koyama I, Sykes M, Winn HJ, Colvin RB, Sachs DH and Cosimi AB. CD154 Blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am. J. Transplantation 2004;4(9):1391-1398.
  • Sykes M, Sandrin M, and Cozzi E. International cooperation on xenotransplantation. Nat. Med. 2004;10(2):119.
  • Kurtz J, Wekerle T, Sykes M. Tolerance in mixed chimerism - a role for regulatory cells? Trends in Immunol. 2004;25(10)518-523.
  • Kurtz J, Shaffer JM, Lie A, Anosova N, Benichou G, Sykes M. Mechanisms of early peripheral CD4 cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: Evidence for anergy and deletion, but not regulatory cells. Blood 2004;103(11):4336-4343.
  • Sykes M, Sandrin M, Cozzi E: Ethics committee of the International Xenotransplantation Association. International Cooperation on Xenotransplantation. Nat. Med. 2004;10(2):119.
  • Lan P, Wang L, Diouf B, Eguchi H, Su H, Bronson R, Sachs DH, Sykes M, Yang Y-G. Induction of human T cell tolerance to porcine xenoantigen through mixed hematopoietic chimerism. Blood 2004;103(10):3964-3969.
  • Nikolic B, Takeuchi Y, Leykin I, Smith RN, Sykes M. Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity. Diabetes 2004;53(2)376-383.
  • Ito H, Takeuchi Y, Shaffer JM, Sykes M. Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and non-irradiated sites. Blood 2004;103(5)1949-1954.
  • Mapara MY, Sykes M. Biology of neoplasia - Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J. Clin. Oncol. 2004;22(6)1136-1151.
  • Takeuchi Y, Ito H, Kurtz J, Wekerle T, Ho L, Sykes M. Earlier low dose TBI or DST overcomes CD8+ T cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L. Am. J. Transplantation 2004;4:31-40.
  • Kim Y-M, Mapara MY, Down JD, Johnson KW, Boisgerault F, Akiyama Y, Benichou G, Pelot M, Zhao G, Sykes M. Graft-versus-host (GVH)-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning. Blood 2004;103:732-739.
  • Yang Y-G, Wood JC, Lan P, Wilkinson, Sykes M, Fishman JA, Patience C. Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice. J. Clin. Invest. 2003;114:695-700.
  • Sykes M. JAKing up immunosuppression [Editorial - News & Views]. Nat. Med. 2003;12:1458-1459.
  • Sykes M, Sandrin M, D'Apice A: Ethics Committee of the International Xenotransplantation Association. Guidelines for Xenotransplantation. New Engl. J. Med. 2003;349:1294-1295.
  • Daly A, McAfee S, Dey BR, Colby C, Schulte L, Yeap B, Sackstein R, Tarbell NF, Sachs DH, Sykes M, Spitzer TR. Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol. Blood Marrow Transplant. 2003;9:373-382.
  • Kawahara T, Ohdan H, Zhao G, Yang Y-G, Sykes M. Peritoneal Cavity B Cells Are Precursors Of Splenic IgM Natural Antibody-Producing Cells. J. Immunol. 2003;171:5406-5414.
  • Koenecke C, Shaffer JM, Alexander SI, Preffer FI, Dombkowski D, Saidman SL, Dey BR, McAffee S, Spitzer TR, Sykes M. NK cell recovery, chimerism, function and recognition in recipients of haploidentical hematopoietic cell transplantation following non-myeloablative conditioning using a humanized anti-CD2 mAb, Medi-507. Exp. Hematol. 2003;31:911-923.
  • Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N, Sachs DH, Sykes M, Spitzer TR. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Bio. Blood Marrow Transplant. 2003;9:320-329.
  • Rubio M-T, Kim Y-m, Sachs T, Mapara MY, Zhao G, Sykes M. Anti-tumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: Critical role for recipient-derived IFN-γ. Blood 2003;102:2300-2307.
  • Kraus AB, Shaffer JM, Toh HC, Preffer FI, Dombkowski D, Saidman S, Colby C, George R, McAfee S, Sackstein R, Dey BR, Spitzer TR, Sykes M. Early host CD8 T-cell recovery and sensitized anti-donor IL-2-producing and cytotoxic T cell responses associated with marrow graft rejection following nonmyeloablative allogeneic bone marrow transplantation. Exp. Hematol. 2003;31:609-621.
  • Zhao Y, Ohdan H, Manilay JO, Sykes M. NK cell tolerance in mixed allogeneic chimeras. J. Immunol. 2003;170:5398-5405.
  • Mapara MY, Kim Y-M, Marx J, Sykes M. DLI-mediated GVL effects in mixed chimeras established with a nonmyeloablative conditioning regimen; extinction of GVL effects following conversion to full donor chimerism. Transplantation 2003;76:297-305.
  • Kurtz J, Lie A, Griffith M, Eysaman S, Shaffer JM, Anosova N, Turka L, Benichou G, Sykes M. Lack of role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells via BMT and anti-CD40L. Am. J. Transplant. 2003;3:804-816.
  • Kim Y-M, Sachs T, Asavaroengchai W, Bronson R, Sykes M. Graft-versus-host disease (GvHD) can be separated from graft-versus-lymphoma effects by controlling lymphocyte trafficking with FTY720. J. Clin. Invest. 2003;111:659-669.
  • Sykes M, d'Apice Anthony, Sandrin M. IXA Ethics Committee: Position paper of the Committee on Ethics of Xenotransplantation for the International Xenotransplantation Association. Xenotransplantation 2003;10:194-203.
  • Zhao Y, Rodriquez-Barbosa JI, Shimizu A, Swenson KG, Sachs DH, Sykes M. Despite efficient intrathymic negative selection of host-reactive T cells, autoimmune disease may develop in porcine thymus-grafted athymic mice: evidence for failure of regulatory mechanisms suppressing autoimmunity. Transplantation 2003;75:1832-1840.
  • Spitzer TR, McAfee S, Dey BR, Colby C, Hope J, Grossberg H, Preffer FI, Shaffer JM, Alexander SI, Sachs DH, Sykes M. Non-myeloablative haploidentical stem cell transplantation using anti-CD2 monoclonal antibody (MEDI-507) based conditioning for refractory hematologic malignancies. Transplantation 2003;75:1748-1751.
  • Sykes M, Auchincloss Jr. H, Sachs DH. Transplantation Immunology. In: Paul WE, editor. Fundamental Immunology (5th edition). Philadelphia, PA: Lippincott-Raven Publishers; 2003, pp. 1481-1555.
  • Rodriguez-Barbosa JI, Zhao Y, Houser S, Zhao G, Sykes M. Fetal porcine thymus engraftment, survival and CD4 reconstitution in αGal-KO mice is impaired in the presence of high levels of antibodies against αGal. Xenotransplantation 2003;10:24-40.
  • Ohdan H, Sykes M. B cell tolerance to xenoantigens. Xenotransplantation 2003;10:98-106.
  • Yang Y-G, Qi J, Wang MG, Sykes M. Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus host disease induced by donor CD8 T cells. Blood 2002;99:4207-4215.
  • Theodore PR, Simon AR, Warrens AN, Sackstein R, Sykes M. Porcine mononuclear cells adhere to human fibonectin independently of VLA-5: implications for donor-specific tolerance induction in xenotransplantation. Xenotransplantation 2002;9:277-289.
  • Spitzer TR, McAfee S, Sackstein R, Colby C, Dey BR, Saidman S, Preffer FI, Alexander S, Sachs DH, Sykes M. Mixed lymphohematopoietic chimerism and delayed donor leukocyte infusions following non-myeloablative conditioning and HLA-matched and mismatched donor bone marrow transplantation. In: Dicke KA & Keating A, editors. Proceedings: 10th Symposium Auto. Blood and Marrow Transplantation. Charlottesville, VA: Carden Jennings Publishing; 2002. pp. 321-332.
  • Kurtz J, Ito H, Wekerle T, Shaffer JM, Sykes M. Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: Lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4+ cells. Am. J. Transplant. 2001;1:339-349.
  • Rodriguez-Barbosa JI, Zhao Y, Barth RN, Zhao G, Arn JS, Sachs DH, Sykes M. Enhanced CD4 reconstitution by grafting neonatal porcine tissue in alternative locations is associated with donor-specific tolerance and suppression of preexisting xenoreactive T cells: Transplantation 2001;72:1223-1231..
  • Mapara MY, Pelot M, Zhao G, Swenson K, Pearson D, Sykes M. Induction of stable long-term mixed hematopoietic chimerism following nonmyeloablative conditioning with T cell-depleting antibodies, cyclophosphamide, and thymic irradiation leads to donor-specific in vitro and in vivo tolerance. Biol. Blood Marrow Transplant. 2001;7:646-655.
  • Ohdan H, Swenson KG, Kitamura H, Yang Y-G, Sykes M. Tolerization of Gala1,3Gal-reactive B cells in pre-sensitized a1,3-galactosyltransferase-deficient mice by nonmyeloablative induction of mixed chimerism. Xenotransplantation 2001;8:227-238.
  • Ohdan H, Yang Y-G, Swenson KG, Kitamura H, Sykes M. T cell and B cell tolerance to Gala1,3Gal-expressing heart xenografts in a1,3-galatosyltransferase-deficient mice by non-myeloablative induction of mixed chimerism. Transplantation 2001;71:1532-1542.
  • Sykes M. Mixed chimerism and transplant tolerance. Immunity 2001;14:417-424.
  • Wekerle T, Kurtz J, Sayegh MH, Ito H, Wells A, Bensigner S, Shaffer JM, Turka LA, Sykes M. Peripheral deletion after bone marrow transplantation with costimulatory blockade has features of both activated-induced cell death and passive cell death. J. Immunol. 2001;166:2311-2316.
  • Ito H, Kurtz J, Shaffer JM, Sykes M. CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependant on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway. J. Immunol. 2001;166:2970-2981.
  • Nikolic B, Cooke D, Zhao G, Sykes M. Both γδ T cells and NK cells inhibit the engraftment of xenogeneic rat bone marrow cells and induction of xenograft tolerance in mice. J. Immunol. 2001;166:1398-1404.
  • Zhao Y, Rodriguez-Barbosa JL, Zhao G, Shaffer JM, Arn JS, Sykes M. Maturation and function of mouse T cells with a transgenic TCR positively selected by highly disparate xenogeneic porcine MHC. Cell. Mol. Biol. 2001;1:217-228.
  • Nikolic B, Khan A, Sykes M. Induction of tolerance by mixed chimerism with non-myeloablative host conditioning: The importance of overcoming intrathymic alloresistance. Biol. Blood Marrow Transplant. 2001;17:144-153.
  • Ohdan H, Swenson KG, Kruger-Gray HS, Yang Y-G, Xu Y, Thall AD, Sykes M. Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Gal α1,3 Gal epitopes in α 1, 3-galactosyltransferase deficient mice. J. Immunol. 2000 165:5518-5529.
  • Nikolic B, Zhao G, Swenson K, Sykes M. A novel application of cyclosporine A in non-myeloablative pre-transplant host conditioning for allogeneic BMT. Blood 2000;96:1166-1172.
  • Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J. Clin. Invest. 2000;105:1289-1298.
  • Spitzer TR, McAfee S, Sackstein R, Colby C, Toh HC, Multani P, Saidman S, Weymouth D, Preffer FI, Poliquin C, Foley A, Cox B, Andrews D, Sachs DH, Sykes M. Intentional induction of mixed chimerism and achievement of anti-tumor responses after non-myeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol. Blood Marrow Transplant. 2000;6:309-320.
  • Wekerle T, Kurtz J, Ito H, Ronquillo JV, Dong V, Zhao G, Shaffer JM, Sayegh MH, Sykes M. Allogeneic bone marrow transplantation with costimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat. Med. 2000;6:464-469.
  • Yang Y-G, Chen AM, Garrett LJ, Sergio JJ, Theodore PR, Awwad M, VerHalen J, Bodine DM, Sachs DH, Sykes M. Development and analysis of transgenic mice expressing porcine hematopoietic cytokines: a model for achieving durable porcine hematopoietic chimerism across an extensive xenogeneic barrier. Xenotransplantation 2000;7:58-64.
  • Warrens AN, Simon AR, Theodore PR, Sachs DH, Sykes M. Cross-species compatibility of intercellular adhesion molecule-1 (CD54) with its ligands. Transplantation 2000;69:394-399.
  • Yang Y-G, Chen AM, Sergio JJ, Zhou Y, Sykes M. Role of antibody-independent complement activation in rejection of porcine bone marrow cells in mice. Transplantation 2000;69:163-165.
  • Manilay JO, Waneck GL, Sykes M. Levels of Ly-49 receptor expression are determined by the frequency of interactions with MHC ligands: evidence against receptor calibration to a "useful" level. J. Immunol. 1999;163:2628-2633.
  • Ohdan H, Yang Y-G, Shimizu A, Swenson KG, Sykes M. Mixed chimerism induced without lethal conditioning prevents T cell- and anti-Gala1,3Gal-mediated graft rejection. J. Clin. Invest. 1999;104:281-290.
  • Pelot MR, Pearson DA, Swenson K, Zhao G, Sachs J, Yang Y-G, Sykes M. Lymphohematopoietic graft-vs-host reactions can be induced without graft-vs-host disease in murine mixed chimeras established with a cyclophosphamide-based non-myeloablative conditioning regimen. Biol. Blood Marrow Transplant. 1999;5:133-143.
  • Dey BR, Yang Y-G, Preffer FI, Shimizu A, Swenson K, Dombkowski D, Sykes M. The fate of donor T-cell receptor transgenic T cells with known host antigen specificity in a graft-versus-host disease model. Transplantation 1999;68:141-149.
  • Sykes M, Preffer FI, McAfee S, Saidman SL, Weymouth D, Andrews D, Colby C, Sackstein R, Sachs DH, Spitzer TR. Mixed lymphohematopoietic chimerism and graft-vs-lymphoma effects are achievable in adult recipients following non-myeloablative therapy and HLA-mismatched donor bone marrow transplantation. Lancet 1999;353:1755-1759.
  • Nikolic B, Gardner JP, Scadden DT, Arn JS, Sachs DH, Sykes M. Normal development in porcine thymus grafts and specific tolerance of human T cells to porcine donor MHC. J. Immunol. 1999;162:3402-3407.
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For a complete list of publications, please visit PubMed.gov