Jun Chen

Positions:

Associate Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1991

Sun Yat Sen University (China)

Postdoctoral Fellow

Stanford University School of Medicine

Publications:

Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.

Cellular heterogeneity is frequently observed in cancer, but the biological significance of heterogeneous tumor clones is not well defined. Using multicolor reporters and CRISPR-Cas9 barcoding, we trace clonal dynamics in a mouse model of sarcoma. We show that primary tumor growth is associated with a reduction in clonal heterogeneity. Local recurrence of tumors following surgery or radiation therapy is driven by multiple clones. In contrast, advanced metastasis to the lungs is driven by clonal selection of a single metastatic clone (MC). Using RNA sequencing (RNA-seq) and in vivo assays, we identify candidate suppressors of metastasis, namely, Rasd1, Reck, and Aldh1a2. These genes are downregulated in MCs of the primary tumors prior to the formation of metastases. Overexpression of these suppressors of metastasis impair the ability of sarcoma cells to colonize the lungs. Overall, this study reveals clonal dynamics during each step of tumor progression, from initiation to growth, recurrence, and distant metastasis.
Authors
Tang, YJ; Huang, J; Tsushima, H; Ban, GI; Zhang, H; Oristian, KM; Puviindran, V; Williams, N; Ding, X; Ou, J; Jung, S-H; Lee, C-L; Jiao, Y; Chen, BJ; Kirsch, DG; Alman, BA
MLA Citation
Tang, Yuning J., et al. “Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.Cell Rep, vol. 28, no. 11, Sept. 2019, pp. 2837-2850.e5. Pubmed, doi:10.1016/j.celrep.2019.08.029.
URI
https://scholars.duke.edu/individual/pub1368140
PMID
31509746
Source
pubmed
Published In
Cell Reports
Volume
28
Published Date
Start Page
2837
End Page
2850.e5
DOI
10.1016/j.celrep.2019.08.029

Allospecific CD4(+) effector memory T cells do not induce graft-versus-host disease in mice.

We studied whether allospecific CD4(+) effector memory T cells (T(EM)) could induce graft-versus-host disease (GVHD) using a novel GVHD model induced solely by CD4(+) T cell receptor transgenic TEa cells. Allospecific T(EM) generated in a lymphopenic host bore a typical memory phenotype. Moreover, these cells were able to elicit a faster and more effective proliferative response on challenge with alloantigen in vitro and to mediate "second-set" skin graft rejection in vivo. However, these allospecific T(EM) were unable to induce GVHD. Allospecific T(EM) recipients became tolerant to alloantigen as a result of clonal deletion. Even though allospecific T(EM) were able to respond to alloantigen initially, the expansion of these cells and inflammatory cytokine production during GVHD were dramatically decreased. The inability of allospecific T(EM) to sustain the alloresponse may be a result of enhanced activation-induced cell death. These observations provide insight into how allospecific CD4(+) T(EM) respond to alloantigen during GVHD and underscore the fundamental differences in alloresponses mediated by allospecific T(EM) in graft rejection and GVHD settings.
Authors
Zhang, P; Wu, J; Deoliveira, D; Chao, NJ; Chen, BJ
MLA Citation
Zhang, Ping, et al. “Allospecific CD4(+) effector memory T cells do not induce graft-versus-host disease in mice.Biol Blood Marrow Transplant, vol. 18, no. 10, Oct. 2012, pp. 1488–99. Pubmed, doi:10.1016/j.bbmt.2012.07.009.
URI
https://scholars.duke.edu/individual/pub764599
PMID
22809867
Source
pubmed
Published In
Biol Blood Marrow Transplant
Volume
18
Published Date
Start Page
1488
End Page
1499
DOI
10.1016/j.bbmt.2012.07.009

Treg-cell expansion: Better to be "naive"

Authors
Chen, BJ
MLA Citation
Chen, B. J. “Treg-cell expansion: Better to be "naive".” Blood, vol. 108, no. 13, Dec. 2006, pp. 3963–64. Scopus, doi:10.1182/blood-2006-09-048447.
URI
https://scholars.duke.edu/individual/pub764926
Source
scopus
Published In
Blood
Volume
108
Published Date
Start Page
3963
End Page
3964
DOI
10.1182/blood-2006-09-048447

Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model

PG490-88 is a semisyntheüc derivative of a novel compound PG490 (triptolide) purified from a Chinese herb (Tripterygium Wilfordii Hook F). Host specific tolerance in vivo was demonstrated in PG490-88-treated BALB/c recipients (H2d, Mls-21, Mls-3") of bone marrow and spleen cells from B10.D2 mice (H2d, Mls-2", Mls-3") by transplantation of recipient or third party neonatal hearts into the pinna of the ears of recipients. The mechanisms of tolerance were studied further in this model. Since all Vβ3 T cells, which recognize the superantigens Mls-2 and Mls-3 and are present in donor B l O.D2 mice but not in recipient BALB/c mice, are activated and cause GVHD in BALB/c recipients, all Vβ3+ T cells are considered host reactive T cells in this model. Therefore, the roles of clonal deletion/anergy can be studied by following the fate of Vβ3 T cells. As shown in the figure, significant numbers of host reactive Vβ3 CD4+ T cells (3.56+1.66 %), which were significant higher than those in normal BALB/c mice (0.27±0.12, P<0.0001) and were comparable with those in normal B l O.D2 mice (6.18±0.51, P>0.05), were present in PG490-88-treated mice. Simulât results were obtained on CD8 T cells. t r(Figure Presented) 6 NomulBALWc 5 OT-d«plet»d bone marrow T 4 OPG49M8 I I 3 ONwrnil BIO D2 BH These results suggest that clonal deletion was not responsible for the observed tolerance induced by PG490-88, In contrast, Vβ3- T cells were completely deleted in the control Tdepleted bone marrow recipients. Vβ3 T cells obtained from PG490-88-treated recipients which were demonstrated to be tolerant to host antigens proliferated normally in response to T cell receptor crosslinking mediated by anti-CD3 antibody. Neither antigen specific nor antigen nonspecific suppressor cells were found in PG490-88-treated mice. Taken together, the host specific tolerance induced by PG490-88 in a murine BMT model is not due to deletion of alloreactive cells. Moreover, suppressor cells are not involved in the maintenance of tolerance. Rather, PG490-88 appears to lead to allotolerance through the induction of a state of antigen specific anergy of the responding T cells.
Authors
Chen, BJ; Cui, X; Fidler, JM; Chao, NJ
MLA Citation
Chen, B. J., et al. “Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.” Blood, vol. 96, no. 11 PART II, Dec. 2000.
URI
https://scholars.duke.edu/individual/pub764678
Source
scopus
Published In
Blood
Volume
96
Published Date

CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice.

A major challenge in allogeneic hematopoietic cell transplantation is how to transfer T-cell immunity without causing graft-versus-host disease (GVHD). Effector memory T cells (CD62L(-)) are a cell subset that can potentially address this challenge because they do not induce GVHD. Here, we investigated how CD62L(-) T cells contributed to phenotypic and functional T-cell reconstitution after transplantation. On transfer into allogeneic recipients, CD62L(-) T cells were activated and expressed multiple cytokines and cytotoxic molecules. CD62L(-) T cells were able to deplete host radioresistant T cells and facilitate hematopoietic engraftment, resulting in enhanced de novo T-cell regeneration. Enhanced functional immune reconstitution was demonstrated in CD62L(-) T-cell recipients using a tumor and an influenza virus challenge model. Even though CD62L(-) T cells are able to respond to alloantigens and deplete host radioresistant immune cells in GVHD recipients, alloreactive CD62L(-) T cells lost the reactivity over time and were eventually tolerant to alloantigens as a result of prolonged antigen exposure, suggesting a mechanism by which CD62L(-) T cells were able to eliminate host resistance without causing GVHD. These data further highlight the unique characteristics of CD62L(-) T cells and their potential applications in clinical hematopoietic cell transplantation.
Authors
Zhang, J; Barefoot, BE; Mo, W; Deoliveira, D; Son, J; Cui, X; Ramsburg, E; Chen, BJ
MLA Citation
Zhang, Jifeng, et al. “CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice.Blood, vol. 119, no. 26, June 2012, pp. 6344–53. Pubmed, doi:10.1182/blood-2011-03-342055.
URI
https://scholars.duke.edu/individual/pub764923
PMID
22596261
Source
pubmed
Published In
Blood
Volume
119
Published Date
Start Page
6344
End Page
6353
DOI
10.1182/blood-2011-03-342055

Research Areas:

Administration, Inhalation
Adoptive Transfer
Adult
Airway Resistance
Algorithms
Animals
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents, Alkylating
Apoptosis
Autoimmune Diseases
B-Lymphocytes
Blood Cell Count
Blood Platelets
Bone Marrow
Bone Marrow Cells
Bone Marrow Purging
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes
Calibration
Cell Count
Cell Death
Cell Differentiation
Cell Division
Cell Separation
Cell Survival
Cell Transplantation
Cells, Cultured
Chemokines
Chimera
Chimerism
Clonal Anergy
Clonal Deletion
Coculture Techniques
Colony-Forming Units Assay
Computer Simulation
Cytokines
DNA
Dendritic Cells
Disease Models, Animal
Diterpenes
Drugs, Chinese Herbal
Ear
Endothelial Cells
Endothelium, Vascular
Epoxy Compounds
Erythrocytes
Escherichia coli
Female
Fetal Blood
Flow Cytometry
Graft Rejection
Graft Survival
Graft vs Host Disease
Graft vs Leukemia Effect
Graft vs Tumor Effect
Growth Hormone
Heart
Hematologic Neoplasms
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Immune System
Immunity
Immunity, Innate
Immunologic Memory
Immunosuppression
Immunosuppressive Agents
Infant
Isoantigens
Kidney
Light
Lipopolysaccharides
Lung
Lymph Nodes
Lymphocyte Activation
Lymphocyte Count
Lymphocyte Depletion
Macrophages, Alveolar
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mice, Knockout
Mice, Transgenic
Models, Animal
Myocardium
Neoplasm Staging
Nephritis
Neutrophil Infiltration
Peptides
Peroxidase
Phantoms, Imaging
Phenanthrenes
Photochemotherapy
Phytotherapy
Pneumonia
Pneumonia, Bacterial
Polymers
Primates
Prodrugs
Pulmonary Alveoli
RNA, Messenger
Radiation Chimera
Radiation Dosage
Radiation Injuries
Radiation Injuries, Experimental
Radiometry
Rats
Receptor, Angiotensin, Type 1
Receptors, Antigen, T-Cell
Recombinant Proteins
Recovery of Function
Reproducibility of Results
Skin
Skin Neoplasms
Skin Transplantation
Specific Pathogen-Free Organisms
Spleen
Stem Cell Transplantation
Stem Cells
Survival Rate
T-Lymphocyte Subsets
T-Lymphocytes
Thymus Gland
Toll-Like Receptor 4
Transplantation Chimera
Transplantation Immunology
Transplantation, Heterologous
Transplantation, Homologous
Tumor Cells, Cultured
Whole-Body Irradiation
Wounds, Penetrating