A photo of Timothy LeCras.

Timothy D. Le Cras, PhD


  • Associate Dean for Graduate Education, University of Cincinnati College of Medicine
  • Professor, UC Department of Pediatrics

About

Biography

Vascular malformations are a kind of abnormal overgrowth or birthmark composed of blood vessels. Both vascular malformations and tumors in children and infants are associated with long-term problems and mortality risk. Further research and understanding of the underlying mechanisms that cause these vascular malformations and tumors are essential for effective treatment of these patients and for saving lives.

My research team studies vascular development as well as vascular malformations and disease. The goal of our research is to examine and find the mechanisms responsible for vascular development, abnormalities and vascular diseases. Our team has significant expertise in analyzing the molecular, genetic and cellular pathways behind human diseases.

In addition, my research lab studies the role of angiogenic factors and gene mutations in endothelial cells and how they lead to advancing the disease processes.

A major strength of our research is that we use human cells and samples to determine disease pathways and to identify new targeted treatments. Interactions with physicians at Cincinnati Children's and other children's hospitals have allowed us to use human blood samples to gain unique insights into disease processes. Recently, we have identified blood biomarkers for complex lymphatic anomalies (kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE)). One of these biomarkers (Angiopoietin-2) is now available as a clinical blood test.

In collaboration with Dr. Boscolo’s laboratory at Cincinnati Children's, we have studied cells from patients and somatic gene mutations in endothelial cells that pinpointed hyper-activated signaling pathways and examined innovative treatment methods.

I have more than 25 years of experience in vascular development research and joined the team at Cincinnati Children’s Hospital Medical Center in 2001. My research has been published in journals such as Pediatric Blood and Cancer, Arteriosclerosis, Thrombosis, and Vascular Biology, American Journal of Respiratory Cell and Molecular Biology and Journal of Clinical Investigation.

Postdoctoral fellow: University of Virginia, Charlottesville, VA, 1993-1996.

PhD: University of Cambridge, UK, 1988-1992.

BSc: Biochemistry, Brunel University, London, UK, 1983-1987.

Interests

Pathogenesis of vascular anomalies; vascular malformations; kaposiform lymphangiomatosis; capillary lymphatic venous malformations; pulmonary hypertension; pulmonary vascular disease; bronchopulmonary dysplasia

Research Areas

Pulmonary Biology

Publications

Kaposiform lymphangiomatosis: Diagnosis, pathogenesis, and treatment. McDaniel, CG; Adams, DM; Steele, KE; Hammill, AM; Merrow, AC; Crane, JL; Smith, CL; Kozakewich, HP W; Le Cras, TD. Pediatric Blood and Cancer. 2023; 70:e30219.

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

Circulating level of Angiopoietin-2 is associated with acute kidney injury in coronavirus disease 2019 (COVID-19). Henry, BM; de Oliveira, MH S; Cheruiyot, I; Benoit, JL; Cooper, DS; Lippi, G; Le Cras, TD; Benoit, SW. Angiogenesis. 2021; 24:403-406.

Kaposiform lymphangiomatosis treated with multimodal therapy improves coagulopathy and reduces blood angiopoietin-2 levels. Crane, J; Manfredo, J; Boscolo, E; Coyan, M; Takemoto, C; Itkin, M; Adams, DM; Le Cras, TD. Pediatric Blood and Cancer. 2020; 67:e28529.

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

Comment on: Potential biomarkers of kaposiform lymphangiomatosis. Le Cras, TD; Adams, DM. Pediatric Blood and Cancer. 2020; 67:e28100.

Early Disruption of VEGF Receptor Signaling and the Risk for Adult Emphysema. Le Cras, TD; Abman, SH. American Journal of Respiratory and Critical Care Medicine. 2020; 201:620-621.

Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis. Boscolo, E; Pastura, P; Glaser, K; Goines, J; Hammill, AM; Adams, DM; Dickie, P; Dickie, BH; Le Cras, TD. Pediatric Blood and Cancer. 2019; 66:e27790.

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

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