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)
  • ATVB Cover Art Award, ATVB (2017)

Professional Education

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

Lab Affiliations

All Publications

  • Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer. Molecular imaging and biology He, H., Chiu, A. C., Kanada, M., Schaar, B. T., Krishnan, V., Contag, C. H., Dorigo, O. 2017


    Tumor-associated macrophages (TAMs) are often associated with a poor prognosis in cancer. To gain a better understanding of cellular recruitment and dynamics of TAM biology during cancer progression, we established a novel transgenic mouse model for in vivo imaging of luciferase-expressing macrophages.B6.129P2-Lyz2(tm1(cre)Ifo)/J mice, which express Cre recombinase under the control of the lysozyme M promoter (LysM) were crossed to Cre-lox Luc reporter mice (RLG), to produce LysM-LG mice whose macrophages express luciferase. Cell-type-specific luciferase expression in these mice was verified by flow cytometry, and via in vivo bioluminescence imaging under conditions where macrophages were either stimulated with lipopolysaccharide or depleted with clodronate liposomes. The distribution of activated macrophages was longitudinally imaged in two immunocompetent LysM-LG mouse models with either B16 melanoma or ID8 ovarian cancer cells.In vivo imaging of LysM-LG mice showed luciferase activity was generated by macrophages. Clodronate liposome-mediated depletion of macrophages lowered overall bioluminescence while lipopolysaccharide injection increased macrophage bioluminescence in both the B16 and ID8 models. Tracking macrophages weekly in tumor-bearing animals after intraperitoneal (i.p.) or intraovarian (i.o.) injection resulted in distinct, dynamic patterns of macrophage activity. Animals with metastatic ovarian cancer after i.p. injection exhibited significantly higher peritoneal macrophage activity compared to animals after i.o. injection.The LysM-LG model allows tracking of macrophage recruitment and activation during disease initiation and progression in a noninvasive manner. This model provides a tool to visualize and monitor the benefit of pharmacological interventions targeting macrophages in preclinical models.

    View details for DOI 10.1007/s11307-017-1061-2

    View details for PubMedID 28233218

  • Perivascular Macrophages Limit Permeability. Arteriosclerosis, thrombosis, and vascular biology He, H., Mack, J. J., Güç, E., Warren, C. M., Squadrito, M. L., Kilarski, W. W., Baer, C., Freshman, R. D., McDonald, A. I., Ziyad, S., Swartz, M. A., De Palma, M., Iruela-Arispe, M. L. 2016; 36 (11): 2203-2212


    Perivascular cells, including pericytes, macrophages, smooth muscle cells, and other specialized cell types, like podocytes, participate in various aspects of vascular function. However, aside from the well-established roles of smooth muscle cells and pericytes, the contributions of other vascular-associated cells are poorly understood. Our goal was to ascertain the function of perivascular macrophages in adult tissues under nonpathological conditions.We combined confocal microscopy, in vivo cell depletion, and in vitro assays to investigate the contribution of perivascular macrophages to vascular function. We found that resident perivascular macrophages are associated with capillaries at a frequency similar to that of pericytes. Macrophage depletion using either clodronate liposomes or antibodies unexpectedly resulted in hyperpermeability. This effect could be rescued when M2-like macrophages, but not M1-like macrophages or dendritic cells, were reconstituted in vivo, suggesting subtype-specific roles for macrophages in the regulation of vascular permeability. Furthermore, we found that permeability-promoting agents elicit motility and eventual dissociation of macrophages from the vasculature. Finally, in vitro assays showed that M2-like macrophages attenuate the phosphorylation of VE-cadherin upon exposure to permeability-promoting agents.This study points to a direct contribution of macrophages to vessel barrier integrity and provides evidence that heterotypic cell interactions with the endothelium, in addition to those of pericytes, control vascular permeability.

    View details for PubMedID 27634833

  • Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer CANCER RESEARCH Moughon, D. L., He, H., Schokrpur, S., Jiang, Z. K., Yaqoob, M., David, J., Lin, C., Iruela-Arispe, M. L., Dorigo, O., Wu, L. 2015; 75 (22): 4742-4752
  • 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

  • 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