A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE
Zeng, Defu, M.D. Research Bookmark and Share

Defu Zeng, M.D. Research

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.
 
 

Defu Zeng, M.D. Lab Members

Defu Zeng, M.D.
Professor
626-246-HOPE (4673) ext. 62587
 
Ruishu Deng, M.D., Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 64432
 
Mingfeng Zhang, Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 64203
 
Jeremy Racine, Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 63713
 
Ya-Jing Xu, M.D.
Visiting Scientist
626-246-HOPE (4673) ext. 64332
 
Heather Johnston
Ph.D. candidate
626-246-HOPE (4673) ext. 62912
 
Xiong Ni
Ph.D. candidate
626-246-HOPE (4673) ext. 61036
 
Kaniel Cassady
Ph.D. student
626-246-HOPE (4673) ext. 64432
 
Hua Jin
International Ph.D. student
626-246-HOPE (4673) ext. 60659
 

Zeng, Defu, M.D. Research

Defu Zeng, M.D. Research

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

Defu Zeng, M.D. Lab Members

Defu Zeng, M.D.
Professor
626-246-HOPE (4673) ext. 62587
 
Ruishu Deng, M.D., Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 64432
 
Mingfeng Zhang, Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 64203
 
Jeremy Racine, Ph.D.
Postdoctoral Fellow
626-246-HOPE (4673) ext. 63713
 
Ya-Jing Xu, M.D.
Visiting Scientist
626-246-HOPE (4673) ext. 64332
 
Heather Johnston
Ph.D. candidate
626-246-HOPE (4673) ext. 62912
 
Xiong Ni
Ph.D. candidate
626-246-HOPE (4673) ext. 61036
 
Kaniel Cassady
Ph.D. student
626-246-HOPE (4673) ext. 64432
 
Hua Jin
International Ph.D. student
626-246-HOPE (4673) ext. 60659
 
Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
NEWS & UPDATES
  • Although a stem cell transplant can be a lifesaving procedure for people diagnosed with a blood cancer or blood disorder, the standard transplant may not be appropriate for all patients. This is because the conditioning regimen (the intensive chemotherapy and/or radiation treatments preceding the transplant) is...
  • Brain tumor removal would seem to be the obvious course of action in the wake of a brain tumor diagnosis, but that’s not always the case. Some tumors are too difficult for many surgeons to reach or too close to areas that control vital functions. Removing them just proves too risky. A new device at City [...
  • Hijacking the same sorts of viruses that cause HIV and using them to reprogram immune cells to fight cancer sounds like stuff of the future. Some scientists believe that the future is closer than we think – and are now studying the approach in clinical trials at City of Hope. Immunotherapy is a promising approa...
  • Nausea is the one of the most well-known, and dreaded, side effects of cancer treatment — and with good reason. Beyond the quality-of-life issues that it causes, severe nausea can prevent patients from receiving enough nutrients and calories at a time when they need every edge they can get. A few simple actions...
  • With Labor Day just around the corner, summer is on its way out. But just because summertime is ending doesn’t mean we can skip sunscreen. Protection from ultraviolet (UV) radiation is needed all year round. Exposure to UV radiation — whether from the sun or from artificial sources such as sunlamps used i...
  • Undergoing reconstructive surgery may seem like a forgone conclusion for survivors of breast cancer, but that doesn’t appear to be the case. A new study has found that most breast cancer survivors who undergo a mastectomy decide against surgical reconstruction of their breasts. The reasons for such a deci...
  • Nearly four decades ago, City of Hope began its bone marrow transplant program. Its first transplant reunion celebration was a single patient and his donor, also his brother. This year, City of Hope welcomed hundreds of hematopoietic cell transplant (HCT) recipients to the annual bone marrow transplant/HCT reun...
  • The burgeoning type 2 diabetes epidemic casts a pall over the health of America’s public. New research now shows the looming threat is getting worse. Much worse. A diabetes trends study published earlier this month in the Lancet Diabetes and Endocrinology by researchers at the federal Centers for Disease Contro...
  • An aspirin a day might help keep breast cancer away for some breast cancer survivors, a new study suggests. Obese women who have had breast cancer could cut their risk of a recurrence in half if they regularly take aspirin or other nonsteroidal anti-inflammatory drugs, called NSAIDs, report researchers from the...
  • Christine Crews isn’t only a fitness enthusiast, she’s also a personal trainer and fitness instructor. Being active defines her life. So when she was diagnosed with bladder cancer at age 30, she decided she absolutely couldn’t let the disease interfere with that lifestyle. And it didn’t. For t...
  • Cancer treatment and the cancer itself can cause changes in your sense of taste or smell. These side effects typically subside after treatment ends, but there are ways to help alleviate those bitter and metallic tastes in your mouth. Here are tips from the National Cancer Institute to help keeps tastes and food...
  • Immunotherapy — using one’s immune system to treat a disease — has been long lauded as the “magic bullet” of cancer treatments, one that can be more effective than the conventional therapies of surgery, radiation or chemotherapy. One specific type of immunotherapy, called adoptive T cell thera...
  • Today, when cancer spreads from its original site to other parts of the body, a process known as metastasis, patients face an uphill battle. Treatments are poorly effective, and cures are nearly impossible. Further, incidence rates for these types of cancers are increasing – particularly for cancers that have s...
  • Thanks to the California Institute for Regenerative Medicine (CIRM), high school students across the state gained valuable hands-on experience with stem cell research this summer. City of Hope hosted eight of those students. As part of the CIRM Creativity Awards program, the young scholars worked full time as m...
  • Radiation therapy can help cure many children facing Hodgkin lymphoma and other cancers. When the radiation is delivered to a girl’s chest, however, it can lead to a marked increase in breast cancer risk later in life. A recent multi-institutional study that included City of Hope’s Smita Bhatia, M.D., M.P.H., t...