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
 
Nainong Li, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Sheng-Li Xue, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Limin Wu, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Qin Lin, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Kaniel Cassady
Ph.D. candidate
626-246-HOPE (4673) ext. 64432
 
Xiong Ni
International Ph.D. candidate
626-246-HOPE (4673) ext. 61036
 
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
 
Nainong Li, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Sheng-Li Xue, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Limin Wu, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Qin Lin, M.D., Ph.D.
Visiting Scientist
626-246-HOPE (4673)
 
Kaniel Cassady
Ph.D. candidate
626-246-HOPE (4673) ext. 64432
 
Xiong Ni
International Ph.D. candidate
626-246-HOPE (4673) ext. 61036
 
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
  • The body’s immune system is usually adept at attacking outside invaders such as bacteria and viruses. But because cancer originates from the body’s own cells, the immune system can fail to see it as foreign. As a result, the body’s most powerful ally can remain largely idle against cancer as the disease progres...
  • On Jan. 1, 2015, five City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the parade is “Inspiring Stories.” Her...
  • Are you thinking about switching from traditional cigarettes to e-cigarettes for the Great American Smokeout? Are you thinking that might be a better option than the traditional quit-smoking route? Think again. For lung expert Brian Tiep, M.D., the dislike and distrust he feels for e-cigs comes down to this: Th...
  • Hematologist Robert Chen, M.D., is boosting scientific discovery at City of Hope and, by extension, across the nation. Just ask the National Cancer Institute. The institution recently awarded Chen the much-sought-after Clinical Investigator Team Leadership Award for boosting scientific discovery at City of Hope...
  • Great strides have been made in treating cancer – including lung cancer – but by the time people show symptoms of the disease, the cancer has usually advanced. That’s because, at early stages, lung cancer has no symptoms. Only recently has lung cancer screening become an option. (Read more about the risks...
  • Identifying cures for currently incurable diseases and providing patients with safe, fast and potentially lifesaving treatments is the focus of City of Hope’s new Alpha Clinic for Cell Therapy and Innovation (ACT-I). The clinic is funded by an $8 million, five-year grant from the California Institute for Regene...
  • Cancer is a couple’s disease. It affects not just the person diagnosed, but his or her partner as well. It also affects the ability of both people to communicate effectively. The Couples Coping with Cancer Together program at City of Hope teaches couples how to communicate and solve problems as a unit. He...
  • Chemotherapy drugs work by either killing cancer cells or by stopping them from multiplying, that is, dividing. Some of the more powerful drugs used to treat cancer do their job by interfering with the cancer cells’ DNA and RNA growth, preventing them from copying themselves and dividing. Such drugs, however, l...
  • During October, everything seems to turn pink – clothing, the NFL logo, tape dispensers, boxing gloves, blenders, soup cans, you name it – in order to raise awareness for what many believe is the most dangerous cancer that affects women: breast cancer. But, in addition to thinking pink, women should...
  • In February 2003, when she was only 16 months old, Maya Gallardo was diagnosed with acute myelogenous leukemia (AML) and, to make matters much worse, pneumonia. The pneumonia complicated what was already destined to be grueling treatment regimen. To assess the extent of her illness, Maya had to endure a spinal ...
  • Former smokers age 55 to 74 who rely on Medicare for health care services have just received a long-hoped-for announcement. Under a proposed decision from the Centers for Medicare and Medicaid Services, they’ll now have access to lung cancer screening with a low-dose CT scan. The proposed decision, announ...
  • City of Hope has a longstanding commitment to combating diabetes, a leading national and global health threat. Already, it’s scored some successes, from research that led to the development of synthetic human insulin – still used by millions of patients – to potentially lifesaving islet cell transplants. Diabet...
  • Dee Hunt never smoked. Neither did her five sisters and brothers. They didn’t have exposure to radon or asbestos, either. That didn’t prevent every one of them from being diagnosed with lung cancer. Their parents were smokers, but they’d all left home more than 30 years before any of them were diagn...
  • They may not talk about it, but women with cancers in the pelvic region, such as cervical cancer, bladder cancer and uterine cancer, often have problems controlling their urine, bowel or flatus. Although they may feel isolated, they’re far from alone. Many other women have such problems, too. In fact, nea...
  • Cancer that spreads to the liver poses a significant threat to patients, and a great challenge to surgeons. The organ’s anatomical complexity and its maze of blood vessels make removal of tumors difficult, even for specialized liver cancer surgeons. Following chemotherapy, the livers of cancer patients are not ...