Experimental Hematology and Cancer Biology
Boscolo Lab

Boscolo Research Lab

Vascular anomalies are congenital defects affecting blood and lymphatic vessel development. These malformations and tumors are disfiguring and life-threatening resulting in severe impairment of the quality of life in young children.

Our research focuses on modeling vascular anomalies in mouse with the use of patient-derived endothelial cells (EC) or with transgenic animal systems that mimic genetic defects found in patients. Our goal is to identify genes and signaling pathways crucial for the formation of vascular anomalies as these discoveries can have the greatest impact on the understanding of processes regulating normal and pathological blood vessel formation. Furthermore, we have a tight collaboration with clinicians to translate our molecular discoveries into targeted therapies for patients affected by vascular anomalies.

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Publications

Selected Publications

Le Cras, TD; Goines, J; Lakes, N; Pastura, P; Hammill, AM; Adams, DM; Boscolo, E. Constitutively active PIK3CA mutations are expressed by lymphatic and vascular endothelial cells in capillary lymphatic venous malformation. Angiogenesis. 2020; 23:425-442.

Cai, Y; Schrenk, S; Goines, J; Davis, GE; Boscolo, E. Constitutive Active Mutant TIE2 Induces Enlarged Vascular Lumen Formation with Loss of Apico-basal Polarity and Pericyte Recruitment. Scientific Reports. 2019; 9.

Li, X; Cai, Y; Goines, J; Pastura, P; Brichta, L; Lane, A; Le Cras, TD; Boscolo, E. Ponatinib Combined With Rapamycin Causes Regression of Murine Venous Malformation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2019; 39:496-512.

Goines, J; Li, X; Cai, Y; Mobberley-Schuman, P; Metcalf, M; Fishman, SJ; Adams, DM; Hammill, AM; Boscolo, E. A xenograft model for venous malformation. Angiogenesis. 2018; 21:725-735.

Boscolo, E; Limaye, N; Huang, L; Kang, K; Soblet, J; Uebelhoer, M; Mendola, A; Natynki, M; Seront, E; Dupont, S; et al. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. Journal of Clinical Investigation. 2015; 125:3491-3504.

Boscolo, E; Coma, S; Luks, VL; Greene, AK; Klagsbrun, M; Warman, ML; Bischoff, J. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation. Angiogenesis. 2015; 18:151-162.

Boscolo, E; Mulliken, JB; Bischoff, J. Pericytes from infantile hemangioma display proangiogenic properties and dysregulated angiopoietin-1. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013; 33:501-509.

Boscolo, E; Mulliken, JB; Bischoff, J. VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a murine model of infantile hemangioma. American Journal of Pathology. 2011; 179:2266-2277.

Boscolo, E; Stewart, CL; Greenberger, S; Wu, JK; Durham, JT; Herman, IM; Mulliken, JB; Kitajewski, J; Bischoff, J. JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011; 31:2181-2192.

Greenberger, S; Boscolo, E; Adini, I; Mulliken, JB; Bischoff, J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. New England Journal of Medicine. 2010; 362:1005-1013.

Khan, ZA; Boscolo, E; Picard, A; Psutka, S; Melero-Martin, JM; Bartch, TC; Mulliken, JB; Bischoff, J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. Journal of Clinical Investigation. 2008; 118:2592-2599.

2022

Boscolo, E; Pastura, P; Schrenk, S; Goines, J; Kang, R; Pillis, D; Malik, P; Le Cras, TD. NRASQ61R mutation in human endothelial cells causes vascular malformations. Angiogenesis. 2022; 25:331-342.

Schrenk, S; Boscolo, E. A transcription factor is the target of propranolol treatment in infantile hemangioma. Journal of Clinical Investigation. 2022; 132.

2021

Goines, J; Boscolo, E. A Xenograft Model for Venous Malformation. . 2021.

2020

Crane, J; Manfredo, J; Boscolo, E; Coyan, M; Takemoto, C; Itkin, M; Adams, DM; Le Cras, TD. Kaposiform lymphangiomatosis treated with multimodal therapy improves coagulopathy and reduces blood angiopoietin-2 levels. Pediatric Blood and Cancer. 2020; 67.

Schrenk, S; Goines, J; Boscolo, E. A Patient-Derived Xenograft Model for Venous Malformation. Journal of Visualized Experiments. 2020.

2019

Boscolo, E; Pastura, P; Glaser, K; Goines, J; Hammill, AM; Adams, DM; Dickie, P; Dickie, BH; Le Cras, TD. Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis. Pediatric Blood and Cancer. 2019; 66.

Le Cras, TD; Boscolo, E. Cellular and molecular mechanisms of PIK3CA-related vascular anomalies. 2019; 1:H33-H40.

Hall, A; Choi, K; Liu, W; Rose, J; Zhao, C; Yu, Y; Na, Y; Cai, Y; Coover, RA; Lin, Y; et al. RUNX represses Pmp22 to drive neurofibromagenesis. Science advances. 2019; 5.

Lakes, N; Goines, J; Pastura, P; Le Cras, T; Boscolo, E. Capillary Lymphatic Venous Malformations are caused by Endothelial‐Specific Gain‐of‐Function Mutations in the PIK3CA Gene. FASEB Journal. 2019; 33:527.3-527.3.

2018

Goines, J; Li, X; Cai, Y; Mobberley-Schuman, P; Metcalf, M; Fishman, SJ; Adams, DM; Hammill, AM; Boscolo, E. A xenograft model for venous malformation. Angiogenesis. 2018; 21:725-735.

Chadwick, ML; Lane, A; Thomas, D; Smith, AR; White, AR; Davidson, D; Feng, Y; Boscolo, E; Zheng, Y; Adams, DM; et al. Combined mTOR and MEK inhibition is an effective therapy in a novel mouse model for angiosarcoma. Oncotarget. 2018; 9:24750-24765.