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
  • On Jan. 1, 2015, six 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.” Repr...
  • When 25-year-old Angelina Mattos was diagnosed with Stage 4 oral cancer earlier this year, she learned that her only hope of survival was through the removal of her tongue, a surgery that leaves people without the ability to talk or eat normally, sometimes permanently ending their ability to speak. After hearin...
  • Two years ago, Joselyn Miller and her family sat together as stem cells from her brother’s bone marrow were infused into her – a precious gift of life that the family is excited to have the chance to pass to another patient in need. Today, the stem cell recipient is healthy. Her 23-year-old son Rex, who […...
  • Even as the overall rate of oral cancers in the United States steadily declines, the rate of tongue cancer is increasing — especially among white females ages 18 to 44. An oral cancer diagnosis, although rare, is serious. Only half of the people diagnosed with oral cancer are still alive after five years, accor...
  • Sometimes cancer found in the lungs is not lung cancer at all. It can be another type of cancer that originated elsewhere in the body and spread, or metastasized, to the lungs through the bloodstream or lymphatic system. These tumors are called lung metastases, or metastatic cancer to the lungs, and are not the...
  • When it comes to research into the treatment of hematologic cancers, City of Hope scientists stand out. One study that  they presented this week at the annual meeting of the American Society of Hematology suggests a new standard of care for HIV-associated lymphoma, another offers promise for the treatment of re...
  • Patients with HIV-associated lymphoma may soon have increased access to the current standard of care for some non-HIV infected patients – autologous stem cell transplants. Impressive new data, presented Monday at the annual meeting of the American Society of Hematology (ASH) in San Francisco, indicate that HIV-...
  • On Jan. 1, 2015, six 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 Rose Parade is “Inspiring Stories.”...
  • The holidays can create an overwhelming urge to give to people in need — especially to sick children and families spending the holidays in a hospital room. That’s a good thing. Holiday donations of toys and gifts can bolster the spirits, and improve the lives, of people affected by illness, and hospitals ...
  • On Jan. 1, 2015, six 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.” Here...
  • Cancer has a way of “talking” to the immune system and corrupting it to work on its own behalf instead of defending the body. Blocking this communication would allow the immune system to see cancer cells for what they are – something to be fought off – and stop them from growing. A breakthrough Scientists [R...
  • On Jan. 1, 2015, six 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.” By V...
  • On Jan. 1, 2015, six 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.” The ...
  • On Jan. 1, 2015, six 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.” In 2...
  • You’ve done the easy stuff – braved the toy store and the Black Friday frenzy, stayed up all night trolling deals online, picked up gift cards for your colleagues at work. There’s just one gift left, the one you’ve been putting off and the one that means so much. What do you give your friend who […]