Zeng Defu

Defu Zeng
§
Professor, Department of Diabetes Immunology
§
Professor, Department of Diabetes
Complications and Metabolism
§
Professor, Department of Hematology &
Hematopoietic Cell Transplantation
Research Focus :
§  Transplantation immune tolerance: mixed chimerism
§  Beta cell regeneration in diabetic mice
§  GVHD and GVL effect
Areas of Expertise
§  Diabetes immunology/autoimmunity
§  In vivo beta cell regeneration
§  Hematology & hematopoietic cell transplantation
PROFESSIONAL
EXPERIENCE
§  2013 to present - Professor, Division of Molecular Diabetes Research,
Beckman Research Institute of City of Hope
§  2013 to present - Professor, Department of Hematology and Hematopoietic
Cell Transplantation, City of Hope, Duarte, CA
§  2008 to 2013 - Associate Professor, Department of Diabetes and Metabolic
Diseases Research, Beckman Research Institute of City of Hope
§  Associate Professor, Department of Hematology & Hematopoietic Cell
Transplantation, City of Hope, Duarte, CA
§  2003 to 2008 - Assistant Professor, Departments of Diabetes/Endocrinology
and Hematology/Bone Marrow Transplantation, Beckman Research Institute of City
of Hope, Duarte, CA
§  2000 to 2003 - Senior Research Scientist, Division of Immunology &
Rheumatology, Department of Medicine, Stanford University School of Medicine,
Stanford, CA
§  1997 to 2000 - Research Associate, Division of Immunology & Rheumatology,
Department of Medicine, Stanford University School of Medicine, Stanford, CA
§  1993 to 1997 - Postdoctoral Research Fellow, Division of Immunology &
Rheumatology, Department of Medicine, Stanford University School of Medicine,
Stanford, CA
§  1990 to 1993 - Assistant Professor, Department of Pathophysiology, Fujian
Medical College, Fuzhou, China
§  1985 to 1990 - Postgraduate Fellow, Department of Pathophysiology, Fujian
Medical College, Fuzhou, China
MEMBER OF THE
FOLLOWING RESEARCH TEAMS
§  Diabetes Complications and Metabolism
§  Hematology & Hematopoietic Cell Transplantation
EDUCATION
LABORATORY
Transplantation Immune Tolerance
Allogeneic
hematopoietic cell transplantation (HCT) is a curative therapy for
hematological malignancies and hereditary disorders as well as refractory
autoimmune diseases. Induction of mixed chimerism via allogeneic HCT is also
one of the most reliable approaches for induction of organ transplantation
tolerance. However, graft-versus-host disease (GVHD) remains a major obstacle
in classical HCT, in which recipients are required to be conditioned with total
body irradiation (TBI) or high dose chemotherapy in order to allow donor stem
cell engraftment. Recent studies have shown that tissue damage and activation
of tissue dendritic cells caused by conditioning TBI or chemotherapy plays a
critical role in induction of GVHD.

One of the
research projects in the Zeng lab is to understand the pathogenesis of GVHD, in
which donor T cells infiltrate the target tissues and mediate damage. Based on
the clinical features, GVHD can be divided into acute and chronic GVHD. New
immunosuppressants have been effective in preventing acute but not chronic
GVHD. The latter remains the major cause of morbidity and mortality of
long-term survivors of classical HCT, and there has been no improvement in
treating chronic GVHD over the past three decades, due to the poor understanding
of its pathogenesis.

We have recently
developed new mouse models of chronic GVHD that can reflect the pathogenesis in
humans. We are currently dissecting the role of allo- and auto-reactive CD4+ T
(Th1, Th2 and Th17), Treg cells, APCs (dendritic and B cells), as well as
autoantibodies in the pathogenesis of chronic GVHD. We are currently testing
whether depletion of donor CD4+ T cells and/or B cells early after HCT can
prevent chronic GVHD. These studies will provide new insights into chronic GVHD
pathogenesis and lead to the development of novel therapies for patients.

Another project
is to develop a radiation-free GVHD preventative conditioning regimen for
induction of mixed chimerism for the therapy of autoimmune diseases (i.e. type
1 diabetes, multiple sclerosis, and lupus). We have observed that induction of
mixed chimerism results in reversal of autoimmunity, elimination of insulitis,
and beta cell regeneration in overt diabetic NOD mice. We are dissecting the
mechanisms whereby mixed chimerism reverses autoimmunity. We are also tracing
the origin of beta cell regeneration after reversal of autoimmunity. Our
studies will provide new insights into transplantation biology and promote the
application of HCT as a curative therapy not only for patients with
hematological malignancies but also for patients with variety of refractory
autoimmune diseases.
LAB MEMBERS
Mingfeng Zhang,
Ph.D.

Research Scientist

626-246-4673 (HOPE) ext. 64203

Ruishu Deng,
M.D., Ph.D.

Postdoctoral Fellow

626-246-4673 (HOPE) ext. 64432

Jian Zhou
Visiting
Scientist
626-246-4673
(HOPE)

Su-Fan Zhou
Visiting
Scientist
626-246-4673
(HOPE)

Kaniel Cassady

Ph.D. Candidate

626-246-4673 (HOPE) ext. 64432

Hua Jin
International
Ph.D. Student

626-246-4673 (HOPE) ext. 60659

QingXiao Song
International
Ph.D. Student
626-246-4673
(HOPE)

Jun Wang
International
Ph.D. Student
626-246-4673
(HOPE)

Yuqing Lu, M.D.
Postdoctoral
Research Fellow
626-246-4673
(HOPE)
AN EXPERT'S VOICE
$2.2 million
grant will benefit graft-versus-host disease research
November 20,
2015
Diabetes
research: From epigenetics to islet cell transplants
January 04, 2014
She lost brother
to graft-versus-host disease; now she fights back
August 09, 2013
Graft-versus-host
disease: Answers for bone marrow transplantation
June 14, 2013
Can donated
marrow do away with type 1 diabetes?
June 21, 2012
PUBLICATIONS
Information
listed here is obtained from Pubmed, a public database; City of Hope is not
responsible for its accuracy.
MEMBERSHIPS
§  American Diabetes Association
§  American Society of Blood and Marrow Transplantation
§  American Society of Transplantation
§  Clinical Immunology Society
§  The American Society of Hematology
§  The American Association of Immunologists