What is the role of macrophages in human body? What do they do under different physiological and pathological settings? During my Ph.D. training with Dr. Luisa Iruela-Arispe, my research was focusing on the biological consequences of the interactions between macrophages and endothelial cells. These two types of cells are known to engage in tight and specific interactions that contribute to vascular and oncogenic diseases. The findings from my work (He et al., 2012, Blood) uncovered a critical role for endothelial cells in the induction of M2- macrophage differentiation, which is relevant to the progression of angiogenesis in both developmental and pathological settings. Subsequently, my research on the association between macrophages and endothelial cells in vivo demonstrated that M2-like resident macrophages play a crucial role in regulating vessel permeability through direct cell-cell interactions.

For postdoctoral research, I'm attempting to apply the knowledge of macrophages to oncology field and focus on the role of macrophages in ovarian cancer. In ovarian cancer, more than 75% of mononuclear immune cells close to a tumor are tumor-associated macrophages (TAMs; Wang et al., 2006). Although it has been suggested that macrophages can potentially promote tumor invasion, migration and angiogenesis, no study has yet extensively addressed the role of macrophages in ovarian cancer (Pollard, 2004). We hypothesize that macrophages mediate tumor growth and metastasis through direct interaction with ovarian cancer cells. They play a potential role in regulating cancer cell proliferation, migration and/or survival. We will establish an in vivo imaging model where macrophages can be traced and monitored and their functions can be broadly explored. Such study will provide information on the various mechanisms by which macrophages affect cancer progression, which potentially will lead to the treatment for ovarian cancer and even other types of cancer.

Honors & Awards

  • Chen Xinmin Foundation Award for Excellent Students, CSU (2004)
  • Excellent Graduation Thesis, CSU (2006)
  • Dr Ursula Mandel Fellowship Award, UCLA (2009)
  • Research Travel Award, UCLA (2013)
  • Philip Whitcome Pre-doctoral Training Program, UCLA (2012)
  • CTSI (Clinical and Translational Science Institute) Publication Award, UCLA (2013)

Professional Education

  • Doctor of Philosophy, University of California Los Angeles (2013)
  • Bachelor of Science, Central South University (2006)

Research & Scholarship

Lab Affiliations



All Publications

  • Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation. Cell Goddard, L. M., Murphy, T. J., Org, T., Enciso, J. M., Hashimoto-Partyka, M. K., Warren, C. M., Domigan, C. K., McDonald, A. I., He, H., Sanchez, L. A., Allen, N. C., Orsenigo, F., Chao, L. C., Dejana, E., Tontonoz, P., Mikkola, H. K., Iruela-Arispe, M. L. 2014; 156 (3): 549-62


    Vascular permeability is frequently associated with inflammation and is triggered by a cohort of secreted permeability factors such as vascular endothelial growth factor (VEGF). Here, we show that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and is independent of VEGF. Global or endothelial-specific deletion of PR blocks physiological vascular permeability in the uterus, whereas misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of an endothelial genome-wide transcriptional profile with chromatin immunoprecipitation sequencing revealed that PR induces an NR4A1 (Nur77/TR3)-dependent transcriptional program that broadly regulates vascular permeability in response to progesterone. Silencing of NR4A1 blocks PR-mediated permeability responses, indicating a direct link between PR and NR4A1. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely, and venous-specific regulation of vascular barrier function that is critical for embryo implantation.

    View details for DOI 10.1016/j.cell.2013.12.025

    View details for PubMedID 24485460

  • Notch1 regulates angio-supportive bone marrow-derived cells in mice: relevance to chemoresistance BLOOD Roodhart, J. M., He, H., Daenen, L. G., Monvoisin, A., Barber, C. L., van Amersfoort, M., Hofmann, J. J., Radtke, F., Lane, T. F., Voest, E. E., Iruela-Arispe, M. L. 2013; 122 (1): 143-153


    Host responses to chemotherapy can induce resistance mechanisms that facilitate tumor regrowth. To determine the contribution of bone marrow-derived cells (BMDCs), we exposed tumor-bearing mice to chemotherapeutic agents and evaluated the influx and contribution of a genetically traceable subpopulation of BMDCs (vascular endothelial-cadherin-Cre-enhanced yellow fluorescent protein [VE-Cad-Cre-EYFP]). Treatment of tumor-bearing mice with different chemotherapeutics resulted in a three- to 10-fold increase in the influx of VE-Cad-Cre-EYFP. This enhanced influx was accompanied by a significant increase in angiogenesis. Expression profile analysis revealed a progressive change in the EYFP population with loss of endothelial markers and an increase in mononuclear markers. In the tumor, 2 specific populations of VE-Cad-Cre-EYFP BMDCs were identified: Gr1?/CD11b? and Tie2high/platelet endothelial cell adhesion moleculelow cells, both located in perivascular areas. A common signature of the EYFP population that exits the bone marrow is an increase in Notch. Inducible inactivation of Notch in the EYFP? BMDCs impaired homing of these BMDCs to the tumor. Importantly, Notch deletion reduced therapy-enhanced angiogenesis, and was associated with an increased antitumor effect of the chemotherapy. These findings revealed the functional significance of a specific population of supportive BMDCs in response to chemotherapeutics and uncovered a new potential strategy to enhance anticancer therapy.

    View details for DOI 10.1182/blood-2012-11-459347

    View details for Web of Science ID 000321909300022

    View details for PubMedID 23690447

  • Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages BLOOD He, H., Xu, J., Warren, C. M., Duan, D., Li, X., Wu, L., Iruela-Arispe, M. L. 2012; 120 (15): 3152-3162


    Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several hematopoietic progenitors. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and toward an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived depending on the contact with the endothelium; removal of the endothelial monolayer results in rapid colony dissolution. We further found that Csf1 produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of Csf1 receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth, and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization toward a proangiogenic phenotype. This work also highlights some of the molecules underlying the M2-like differentiation, a process that is relevant to the progression of both developmental and pathologic angiogenesis.

    View details for DOI 10.1182/blood-2012-04-422758

    View details for Web of Science ID 000311619300034

    View details for PubMedID 22919031

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