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
  • To say that myelofibrosis patients need more treatment options would be an understatement. The severely low platelet counts, known as thrombocytopenia, that are one of the hallmark symptoms of the disease can lead to chronic fatigue and weakness that not only damage quality of life but, ultimately, shorten life...
  • Patients with metastatic colorectal cancer often stop responding to the primary drugs used against the disease, leaving them with few options and little hope. Determined to increase those options, doctors and researchers at City of Hope are conducting two clinical trials that could lead to new treatments for pe...
  • Investigators working at City of Hope are making many significant inroads against many forms of cancer. To do that, they have to take a variety of approaches. Molecular oncology researchers focus on abnormal cancer-associated activity in a cell’s nucleus. One especially prominent factor in many breast and ovari...
  • In light of the new breast cancer screening guidelines, which call for women to have mammograms every other year from age 50 to 74, it’s more important than ever for women to understand their individual risk. On Monday, the U.S. Preventive Services Task force released new breast cancer screening guideline...
  • Cancer patients need, and deserve, more than medical care. They and their families need high-quality supportive care – that is, care that addresses their physical, emotional and spiritual well-being. Health care professionals increasingly understand this, but starting such programs from scratch isn’t easy...
  • Each year, City of Hope patients given another chance at life gather to pose for a picture like this one. Going on its 39th year, the celebration of patients free of blood cancers thanks to bone marrow or stem cell transplants has grown such that a photographer has to scale a cherry picker just to […]
  • Cancer patients who are participating in early-stage clinical trials need extra emotional and physical support due to their additional stress and often unique symptoms. Now an effort by researchers at City of Hope to create a model for such support has received a $6.8 million grant from the National Cancer Inst...
  • The need for improvements in treating malignant brain tumors has never been greater. Survival for many patients with these tumors are sometimes measured in just months. One reason that therapeutic options are limited is that traditional surgery is deemed too risky for many brain tumors, especially for those in ...
  • “Honestly, there’s nothing special about my story,” protested Daniel Samson, as he bounced Layla, his 3 1/2-year-old daughter, on his lap and put on a video for her to watch. “I just want to tell it for my own sake, and share it with other men who may be going through this chaos.” Samson spoke […]
  • As far back as he can remember, Jonathan Yamzon, M.D., wanted to be a doctor. “I knew it from the get-go,” he said, matter-of-factly. “I always envisioned it as the ideal; the supreme thing one could do with one’s life.” The youngest of six children, Yamzon was barely a toddler when his family moved to [&...
  • There’s never a “good” time for cancer to strike. With testicular cancer, the timing can seem particularly unfair. This disease targets young adults in the prime of life; otherwise healthy people unaccustomed to any serious illness, let alone cancer. And suddenly … “I can only imagine what they must...
  • Sure, a healthy lifestyle can lower a person’s risk, but the impact of specific actions is harder to tease out. Diet, exercise, tobacco use, nutritional supplements, alcohol consumption … How important are each of these factors, individually? Does strict adherence to (or rejection of) one get you a pass o...
  • Health care decisions are tough. They’re even tougher when you – or loved ones – have to make them without a plan or a conversation. National Healthcare Decisions Day, on April 16,  is a nationwide initiative to demystify the health care decision-making process and encourage families to start talking. Ult...
  • The statistics, direct from the American Cancer Society, are sobering: Cancer death rates among African-American men are 27 percent higher than for white men. The death rate for African-American women is 11 percent higher compared to white women. Hispanics have higher rates of cervical, liver and stomach cancer...
  • “Lucky” is not usually a term used to describe someone diagnosed with cancer.  But that’s how 34-year-old Alex Camargo’s doctor described him when he was diagnosed with thyroid cancer — the disease is one of the most treatable cancers at all stages. That doctor was ultimately proved righ...