James Chen is a clinical fellow in Oncology at Stanford. He graduated summa cum laude in Microbiology, Immunology, and Molecular Genetics from UCLA. He trained as an undergraduate in Hong Wu's Lab, where he studied PTEN’s role in T acute lymphoblastic leukemia. From there, he joined the medical scientist training program at Stanford University where he joined the Weissman lab to pursue his research interests in hematopoietic stem cells and bone marrow transplant. After completing his medical and graduate degrees, James joined Forty Seven Inc., a biotechnology startup, as part of a team to bring novel immunotherapy agents through multiple phases of pre-clinical and clinical development for application in malignancies and hematopoietic stem cell transplantation. To further pursue his goal of translating basic research into clinical practice, he completed his internal medicine residency program at Massachusetts General Hospital. As a fellow, James aims to continue bridging the basic, translation, and clinical research spaces, especially in support of early-phase first-in-human studies.

Clinical Focus

  • Fellow

Honors & Awards

  • Ruth L. Kirschstein National Research Service Award, NIH NHLBI (2014-2017)
  • Beckman Scholar, Arnold and Mabel Beckman Foundation (2007-2008)
  • Phi Beta Kappa, University of California Los Angeles (2008)
  • Wasserman Scholar, Edith and Lew Wasserman Foundation (2007)
  • Irving Stone Research Award, University of California Los Angeles (2006)
  • Gina Finzi Fellow, Gina Finzi Memorial Foundation (2007)

Boards, Advisory Committees, Professional Organizations

  • President, Stanford Medical Student Association (SMSA) (2013 - 2014)
  • Vice President of Operations, Stanford Medical School Association (SMSA) (2011 - 2013)

Professional Education

  • Residency, Massachusetts General Hospital (2020)
  • Internship, Massachusetts General Hospital (2019)
  • MD, Stanford University School of Medicine (2018)
  • PhD, Stanford University School of Medicine, Stem Cell Biology and Regenerative Medicine (2016)
  • BS, University of California Los Angeles, Microbiology, Immunology, and Molecular Genetics (2008)

Lab Affiliations

All Publications

  • Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment. Biochemical and biophysical research communications Sakamaki, T. n., Kao, K. S., Nishi, K. n., Chen, J. Y., Sadaoka, K. n., Fujii, M. n., Takaori-Kondo, A. n., Weissman, I. L., Miyanishi, M. n. 2021; 539: 34–41


    Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field have allowed us to analyze HSCs with single cell resolution and implicate that functional heterogeneity may exist even within the highly purified HSC compartment. However, due in part to the technical limitations of analyzing extremely rare populations and our incomplete understanding of HSC biology, neither the biological meaning of why heterogeneity exists nor the precise mechanism of how heterogeneity is determined within the HSC compartment is entirely known. Here we show the first evidence that self-renewal capacity varies with the degree of replication stress dose and results in heterogeneity within the HSC compartment. Using the Hoxb5-reporter mouse line which enables us to distinguish between long-term (LT)-HSCs and short-term (ST)-HSCs, we have found that ST-HSCs quickly lose self-renewal capacity under high stress environments but can maintain self-renewal under low stress environments for long periods of time. Critically, exogeneous Hoxb5 expression confers protection against loss of self-renewal to Hoxb5-negative HSCs and can partially alter the cell fate of ST-HSCs to that of LT-HSCs. Our results demonstrate that Hoxb5 imparts functional heterogeneity in the HSC compartment by regulating self-renewal capacity. Additionally, Hoxb5-positive HSCs may exist as fail-safe system to protect from the exhaustion of HSCs throughout an organism's lifespan.

    View details for DOI 10.1016/j.bbrc.2020.12.077

    View details for PubMedID 33418191

  • An All Antibody Approach for Conditioning Bone Marrow for Hematopoietic Stem Cell Transplantation with Anti-cKIT and Anti-CD47 in Non-Human Primates Marjon, K. D., Chen, J. Y., Duan, J., Choi, T. S., Sompalli, K., Feng, D., Mata, O., Chen, S., Kean, L., Chao, M., Chao, M., Takimoto, C. H., Agoram, B., Dunbar, C. E., Majeti, R., Weissman, I. L., Liu, J., Volkmer, J. AMER SOC HEMATOLOGY. 2019
  • First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers JOURNAL OF CLINICAL ONCOLOGY Sikic, B., Lakhani, N., Patnaik, A., Shah, S. A., Chandana, S. R., Rasco, D., Colevas, A., O'Rourke, T., Narayanan, S., Papadopoulos, K., Fisher, G. A., Villalobos, V., Prohaska, S. S., Howard, M., Beeram, M., Chao, M. P., Agoram, B., Chen, J. Y., Huang, J., Axt, M., Liu, J., Volkmer, J., Majeti, R., Weissman, I. L., Takimoto, C. H., Supan, D., Wakelee, H. A., Aoki, R., Pegram, M. D., Padda, S. K. 2019; 37 (12): 946-+
  • The Macrophage "Do not eat me' signal, CD47, is a clinically validated cancer immunotherapy target ANNALS OF ONCOLOGY Takimoto, C. H., Chao, M. P., Gibbs, C., McCamish, M. A., Liu, J., Chen, J. Y., Majeti, R., Weissman, I. L. 2019; 30 (3): 486–89
  • CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma NEW ENGLAND JOURNAL OF MEDICINE Advani, R., Flinn, I., Popplewell, L., Forero, A., Bartlett, N. L., Ghosh, N., Kline, J., Roschewski, M., LaCasce, A., Collins, G. P., Thu Tran, Lynn, J., Chen, J. Y., Volkmer, J., Agoram, B., Huang, J., Majeti, R., Weissman, I. L., Takimoto, C. H., Chao, M. P., Smith, S. M. 2018; 379 (18): 1711–21
  • Where Hematopoietic Stem Cells Live: The Bone Marrow Niche ANTIOXIDANTS & REDOX SIGNALING Szade, K., Gulati, G. S., Chan, C. F., Kao, K. S., Miyanishi, M., Marjon, K. D., Sinha, R., George, B. M., Chen, J. Y., Weissman, I. L. 2018


    Hematopoietic stem cells (HSCs) can sustain the production of blood throughout one's lifetime. However, for proper self-renewal of its own population and differentiation to blood, the HSC requires a specialized microenvironment called the "niche." Recent Advances: Recent studies using novel mouse models have shed new light on the cellular architecture and function of the HSC niche. Here, we review the different cells that constitute the HSC niche and the molecular mechanisms that underlie HSC and niche interaction. We discuss the evidence and potential features that distinguish the HSC niche from other microenvironments in the bone marrow. The relevance of the niche in malignant transformation of the HSCs and harboring cancer metastasis to the bone is also outlined. In addition, we address how the niche may regulate reactive oxygen species levels surrounding the HSCs. Critical Issues and Future Directions: We propose future directions and remaining challenges in investigating the niche of HSCs. We discuss how a better understanding of the HSC niche may help in restoring an aged hematopoietic system, fighting against malignancies, and transplanting purified HSCs safely and effectively into patients. Antioxid. Redox Signal. 00, 000-000.

    View details for PubMedID 29113449

  • Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nature immunology Barkal, A. A., Weiskopf, K. n., Kao, K. S., Gordon, S. R., Rosental, B. n., Yiu, Y. Y., George, B. M., Markovic, M. n., Ring, N. G., Tsai, J. M., McKenna, K. M., Ho, P. Y., Cheng, R. Z., Chen, J. Y., Barkal, L. J., Ring, A. M., Weissman, I. L., Maute, R. L. 2017


    Exciting progress in the field of cancer immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component β2-microglobulin (β2M) by cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines the MHC class I-LILRB1 signaling axis as an important regulator of the effector function of innate immune cells, a potential biomarker for therapeutic response to agents directed against the signal-regulatory protein CD47 and a potential target of anti-cancer immunotherapy.

    View details for PubMedID 29180808

  • Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche NATURE Chen, J. Y., Miyanishi, M., Wang, S. K., Yamazaki, S., Sinha, R., Kao, K. S., Seita, J., Sahoo, D., Nakauchi, H., Weissman, I. L. 2016; 530 (7589): 223-?


    Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs.

    View details for DOI 10.1038/nature16943

    View details for Web of Science ID 000369916700040

    View details for PubMedID 26863982

    View details for PubMedCentralID PMC4854608

  • Prospective isolation of human erythroid lineage-committed progenitors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Mori, Y., Chen, J. Y., Pluvinage, J. V., Seita, J., Weissman, I. L. 2015; 112 (31): 9638-9643


    Determining the developmental pathway leading to erythrocytes and being able to isolate their progenitors are crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Here we show that the human erythrocyte progenitor (hEP) can be prospectively isolated from adult bone marrow. We found three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage(-) CD34(+) CD38(+) IL-3Rα(-) CD45RA(-)) population. Both CD71(-) CD105(-) and CD71(+) CD105(-) MEPs, at least in vitro, still retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter subpopulation is skewed in differentiation toward the erythroid lineage. Notably, the proliferative and differentiation output of the CD71(intermediate(int)/+) CD105(+) subset of cells within the MEP population was completely restricted to the erythroid lineage with the loss of MegK potential. CD71(+) CD105(-) MEPs are erythrocyte-biased MEPs (E-MEPs) and CD71(int/+) CD105(+) cells are EPs. These previously unclassified populations may facilitate further understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage.

    View details for DOI 10.1073/pnas.1512076112

    View details for PubMedID 26195758

  • CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America Cheah, M. T., Chen, J. Y., Sahoo, D., Contreras-Trujillo, H., Volkmer, A. K., Scheeren, F. A., Volkmer, J., Weissman, I. L. 2015; 112 (15): 4725-4730


    Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found that CD14-high cancer cells express higher levels of numerous inflammation mediators and form larger tumors compared with CD14-low cells. CD14 antigen is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein and has been shown to be critically important in the signaling pathways of Toll-like receptor (TLR). CD14 expression in this BC subpopulation of cancer cells is required for increased cytokine production and increased tumor growth. Furthermore, tumors formed by CD14-high cells are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14-high BC cells recruit and polarize monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14-low BC cells have a higher baseline cell division rate than CD14-high cells. Importantly, CD14-high cells produce factors that further increase the proliferation of CD14-low cells. Collectively, we demonstrate that CD14-high BC cells may orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.

    View details for DOI 10.1073/pnas.1424795112

    View details for PubMedID 25825750

  • Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk. Proceedings of the National Academy of Sciences of the United States of America Feng, M., Chen, J. Y., Weissman-Tsukamoto, R., Volkmer, J., Ho, P. Y., McKenna, K. M., Cheshier, S., Zhang, M., Guo, N., Gip, P., Mitra, S. S., Weissman, I. L. 2015; 112 (7): 2145-2150


    Macrophage-mediated programmed cell removal (PrCR) is an important mechanism of eliminating diseased and damaged cells before programmed cell death. The induction of PrCR by eat-me signals on tumor cells is countered by don't-eat-me signals such as CD47, which binds macrophage signal-regulatory protein α to inhibit phagocytosis. Blockade of CD47 on tumor cells leads to phagocytosis by macrophages. Here we demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance PrCR. Bruton's tyrosine kinase (Btk) mediates TLR signaling in macrophages. Calreticulin, previously shown to be an eat-me signal on cancer cells, is activated in macrophages for secretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the cancer cells themselves do not express calreticulin.

    View details for DOI 10.1073/pnas.1424907112

    View details for PubMedID 25646432

  • Identification and specification of the mouse skeletal stem cell. Cell Chan, C. K., Seo, E. Y., Chen, J. Y., Lo, D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T., Lu, W., Senarath-Yapa, K., Chung, M. T., Marecic, O., Tran, M., Yan, K. S., Upton, R., Walmsley, G. G., Lee, A. S., Sahoo, D., Kuo, C. J., Weissman, I. L., Longaker, M. T. 2015; 160 (1-2): 285-298


    How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

    View details for DOI 10.1016/j.cell.2014.12.002

    View details for PubMedID 25594184

  • Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chan, C. K., Lindau, P., Jiang, W., Chen, J. Y., Zhang, L. F., Chen, C., Seita, J., Sahoo, D., Kim, J., Lee, A., Park, S., Nag, D., Gong, Y., Kulkarni, S., Luppen, C. A., Theologis, A. A., Wan, D. C., DeBoer, A., Seo, E. Y., Vincent-Tompkins, J. D., Loh, K., Walmsley, G. G., Kraft, D. L., Wu, J. C., Longaker, M. T., Weissman, I. L. 2013; 110 (31): 12643-12648


    Organs are composites of tissue types with diverse developmental origins, and they rely on distinct stem and progenitor cells to meet physiological demands for cellular production and homeostasis. How diverse stem cell activity is coordinated within organs is not well understood. Here we describe a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bone marrow tissue of fetal, neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage-forming) and osteogenic (bone-forming) cells and at least three subsets of stromal cells that exhibit differential expression of cell surface markers, including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)], and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal subsets exhibit differential capacities to support hematopoietic (blood-forming) stem and progenitor cells. Although the 6C3-expressing subset demonstrates functional stem cell niche activity by maintaining primitive hematopoietic stem cell (HSC) renewal in vitro, the other stromal populations promote HSC differentiation to more committed lines of hematopoiesis, such as the B-cell lineage. Gene expression analysis and microscopic studies further reveal a microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma collaborate to provide cytokine signaling to HSCs and more committed hematopoietic progenitors. As a result, within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including HSC supportive 6C3(+) niche cells.

    View details for DOI 10.1073/pnas.1310212110

    View details for PubMedID 23858471

  • Do pluripotent stem cells exist in adult mice as very small embryonic stem cells? Stem cell reports Miyanishi, M., Mori, Y., Seita, J., Chen, J. Y., Karten, S., Chan, C. K., Nakauchi, H., Weissman, I. L. 2013; 1 (2): 198-208


    Very small embryonic-like stem cells (VSELs) isolated from bone marrow (BM) have been reported to be pluripotent. Given their nonembryonic source, they could replace blastocyst-derived embryonic stem cells in research and medicine. However, their multiple-germ-layer potential has been incompletely studied. Here, we show that we cannot find VSELs in mouse BM with any of the reported stem cell potentials, specifically for hematopoiesis. We found that: (1) most events within the "VSEL" flow-cytometry gate had little DNA and the cells corresponding to these events (2) could not form spheres, (3) did not express Oct4, and (4) could not differentiate into blood cells. These results provide a failure to confirm the existence of pluripotent VSELs.

    View details for DOI 10.1016/j.stemcr.2013.07.001

    View details for PubMedID 24052953

  • Suppression of leukemia development caused by PTEN loss PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Guo, W., Schubbert, S., Chen, J. Y., Valamehr, B., Mosessian, S., Shi, H., Dang, N. H., Garcia, C., Theodoro, M. F., Varella-Garcia, M., Wu, H. 2011; 108 (4): 1409-1414


    Multiple genetic or molecular alterations are known to be associated with cancer stem cell formation and cancer development. Targeting such alterations, therefore, may lead to cancer prevention. By crossing our previously established phosphatase and tensin homolog (Pten)-null acute T-lymphoblastic leukemia (T-ALL) model onto the recombination-activating gene 1(-/-) background, we show that the lack of variable, diversity and joining [V(D)J] recombination completely abolishes the Tcrα/δ-c-myc translocation and T-ALL development, regardless of β-catenin activation. We identify mammalian target of rapamycin (mTOR) as a regulator of β-selection. Rapamycin, an mTOR-specific inhibitor, alters nutrient sensing and blocks T-cell differentiation from CD4(-)CD8(-) to CD4(+)CD8(+), the stage where the Tcrα/δ-c-myc translocation occurs. Long-term rapamycin treatment of preleukemic Pten-null mice prevents Tcrα/δ-c-myc translocation and leukemia stem cell (LSC) formation, and it halts T-ALL development. However, rapamycin alone fails to inhibit mTOR signaling in the c-Kit(mid)CD3(+)Lin(-) population enriched for LSCs and eliminate these cells. Our results support the idea that preventing LSC formation and selectively targeting LSCs are promising approaches for antileukemia therapies.

    View details for DOI 10.1073/pnas.1006937108

    View details for Web of Science ID 000286594800040

    View details for PubMedID 21212363

    View details for PubMedCentralID PMC3029702

  • Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation NATURE Guo, W., Lasky, J. L., Chang, C., Mosessian, S., Lewis, X., Xiao, Y., Yeh, J. E., Chen, J. Y., Iruela-Arispe, M. L., Varella-Garcia, M., Wu, H. 2008; 453 (7194): 529-U7


    Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance. The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self-renewable leukaemia stem cells (LSCs) are enriched in the c-Kit(mid)CD3(+)Lin(-) compartment, where unphosphorylated beta-catenin is significantly increased. Conditional ablation of one allele of the beta-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the beta-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit(mid)CD3(+)Lin(-) LSCs and CD3(+) leukaemic blasts, recapitulating a subset of human T-ALL. No alterations in Notch1 signalling are detected in this model, suggesting that Pten inactivation and c-myc overexpression may substitute functionally for Notch1 abnormalities, leading to T-ALL development. Our study indicates that multiple genetic or molecular alterations contribute cooperatively to LSC transformation.

    View details for DOI 10.1038/nature06933

    View details for Web of Science ID 000256023700044

    View details for PubMedID 18463637

    View details for PubMedCentralID PMC2840044