Photo of Timothy Hla,  PhD

Timothy Hla, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2179


timothy.hla@childrens.harvard.edu

Timothy Hla, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Patricia K. Donahoe Professor, Surgery, Harvard Medical School
  • Investigator, Vascular Biology Program, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our laboratory has studied the role of lipid mediators in vascular system, inflammation, and cancer. We cloned the human cyclooxyrgenase-2 (COX-2) cDNA and showed that this gene is correlated with chronic inflammatory conditions and various cancers. We also developed a mouse model in which COX-2 is over expressed and showed that the induction of COX-2 is a major progression factor in tumorigenesis. A second area of research that we contributed is the area of sphingolipid signaling. My laboratory cloned and characterized the first sphingosine 1-phosphate (S1P) receptor and characterized the biology of this signaling system in vascular development, angiogenesis, inflammation, and vascular homeostasis. This receptor is critical for adaptive immune cell trafficking and inhibitors of this receptor have entered the clinic to treat autoimmune diseases. We are exploring the biology of this lipid mediator in vascular and immune systems, and developing novel therapeutic strategies based on the S1P pathway.

Publications

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  • Mendoza A, Fang V, Chen C, Serasinghe M, Verma A, Muller J, Chaluvadi VS, Dustin ML, Hla T, Elemento O, Chipuk JE, Schwab SR. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells. Nature 2017; 546:158-161. PubMed
  • Yanagida K, Liu CH, Faraco G, Galvani S, Smith HK, Burg N, Anrather J, Sanchez T, Iadecola C, Hla T. Size-selective opening of the blood-brain barrier by targeting endothelial sphingosine 1-phosphate receptor 1. Proc Natl Acad Sci U S A 2017. PubMed
  • Yanagida K, Hla T. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. Annu Rev Physiol 2016; 79:67-91. PubMed
  • Ding BS, Liu CH, Sun Y, Chen Y, Swendeman SL, Jung B, Chavez D, Cao Z, Christoffersen C, Nielsen LB, Schwab SR, Rafii S, Hla T. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver. JCI Insight 2016; 1:e87058. PubMed
  • Christensen PM, Liu CH, Swendeman SL, Obinata H, Qvortrup K, Nielsen LB, Hla T, Di Lorenzo A, Christoffersen C. Impaired endothelial barrier function in apolipoprotein M-deficient mice is dependent on sphingosine-1-phosphate receptor 1. FASEB J. 2016; 30:2351-9. PubMed
  • Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T.. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 2015; 523(7560):342-6.
  • Yanagida K, Hla T.. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. 2016.