The Arispe’s laboratory has focused in elucidating the molecular mechanisms that regulate vascular morphogenesis during development and in disease. Towards this goal, this lab contributed to the literature that proved that thrombospondin1 is a highly effective physiological inhibitor of angiogenesis (Iruela-Arispe et al., 1990; 1991; 1996; 1999; Streit et al., 2000; Rodriguez-Manzaneque et al., 2001). Subsequently, using the anti-angiogenic motifs of thrombospondin, the lab cloned two members of the ADAMTS family and demonstrated that the proteins harbor angiostatic properties (Vazquez et al., 1999; Iruela-Arispe et al., 1999; Carpizo and Iruela-Arispe, 2000). In an effort to clarify the vascular effects of ADAMTS proteases, they contributed to current understanding of the biology of this family of extracellular proteases (Rodriguez-Manzaneque et al., 2000; Lee et al., 2005; 2006). Today a pubmed search on “ADAMTS” retrieves 1264 publications. The group is proud to have cloned the first human member of this family and generated many of the initial reagents that have been broadly distributed to entice and facilitate the entrance of so many investigators into this field.
The antagonistic relationship between TSP and VEGF let the group to investigate VEGF association with extracellular matrix proteins. They revealed that activation of VEGFR2 by VEGF varies significantly depending upon the association of VEGF with matrix proteins (Lee et al., 2005; Lee et al., 2010). Furthermore, they identified highly significant intracrine signaling loop that is critical for endothelial cell survival (Lee et al., 2007).
Through an effort to generate valuable Cre-recombinase models for excision of genes in the endothelium (Alva et al., 2006; Monvoisin et al., 2006), the group demonstrated by lineage tracing that hemogenic endothelium gives rise to hematopoietic progenitor cells (Zovein et al., 2008). They have continued to investigate the functional interactions between endothelial cells and hematopoietic cells and uncovered important heterotypic interactions between endothelial cells and macrophages (He et al., 2012).
A more recent focus of the lab has been on the regulation of Notch signaling in the vasculature. Initially, the lab contributed to the literature that demonstrated the critical role of this pathway in tip/stalk cell specification (Hellstrom et al., 2007). In addition, through endothelial and smooth muscle cell inactivation of Jag1, they clarified the vascular roots for the cardiac (endothelial – related) and liver (smooth muscle cell – related) pathologies in Alagille syndrome (Hofmann et al., 2010; 2012). This work highlighted the relevance of heterotypic vascular-parenchymal interactions in the architecture of organs. More recently this trajectory resulted in a greater understanding of how Notch signaling skews differentiation of Pax1+ somitic cells into smooth muscle cells (Briot et al., 2014). These findings shed light into the possible causes of vascular calcification and uncover potential directions for therapeutic development.
Currently, the laboratory is investigating the mechanisms behind the formation of vascular tumors and vascular anomalies. In particular, the group is interested in the identification of critical regulatory nodes that maintain vascular homeostasis and control endothelial proliferation in the context of flow. An additional focus of the lab is to dissect the molecular interactions between endothelial and tumor cells during the process of metastasis with particular emphasis on endothelial barrier.
About the Principal Investigator
Dr. Iruela-Arispe is Professor and Vice-chair of the Molecular, Cell and Developmental Biology, Director of the Molecular Biology Institute and Chair of the Molecular Biology Inter-Departmental Graduate Program at UCLA.
Born in Spain, she immigrated to South America attending school in Argentina and Brazil. She received her Ph.D. in 1989 and followed post-doctoral training at the University of Washington in Seattle. From 1994-1998 she was Assistant Professor at Harvard Medical School and subsequently joined UCLA in 1998.
Her research focuses on the molecular mechanisms that regulate angiogenesis during development and in pathological conditions. She has communicated her work in more than 140 papers, 30 reviews and book chapters. She was the first recipient of the Judah Folkman award (2009) and was President of the North American Vascular Biology Organization (2006-2007). Teaching undergraduate students for the last 17 years, she has received the Distinguished Teaching Award and the Gold Shield Award, the most prestigious prizes given to a faculty at UCLA, for her exemplary teaching and didactic innovations.