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Lab Members

Andreane Cartier

Research Fellow, Vascular Biology Program, Boston Children's Hospital
Research Fellow, Harvard Medical School
Andreane Cartier, Ph.D.
I did my PhD in the lab of Dr Jean-Luc Parent in Sherbrooke, Quebec. I characterized a newly identified interacting protein (WDR36) of the beta isoform of the thromboxane A2 receptor (TPβ), a GPCR that regulates platelets aggregation and vascular smooth muscle cells constriction.
 
My training with Dr Timothy Hla gives me the opportunity to apply to mouse models my knowledge of GPCR signaling, molecular biology and transcriptional gene regulation.
 
Project 1. Role of endothelial cell S1P1 and S1P2 receptors in tumor angiogenesis and tumor growth.
 
Project 2. Whole genome siRNA screen to identify new targets of the endocytic pathway of S1P1 induced by Fingolimod, a synthetic functional antagonist of S1P1 and FDA approved molecule, currently used as a treatment for multiple sclerosis.
 
Project 3. Role of S1P1 and S1P2 in vascular dysfunction caused by a chronic inflammatory environment in vitro and in vivo, and how the imbalance of these two receptors leads to endothelial dysfunction and vascular injury, key processes in cardiovascular diseases development.
 
Publications Highlights
Binda C, Génier S, Cartier A, Larrivée JF, Stankova J, Young JC and Parent JL. A G protein-coupled receptor and the intracellular synthase of its agonist functionally cooperate. J Cell Biol. 2014 Feb 3;204(3):377-93.
 
Lachance V, Cartier A, Génier S, Munger S, Germain P, Labrecque P and Parent JL. Regulation of b2-adrenergic receptor maturation and anterograde trafficking by an interaction with Rab geranylgeranyltransferase: modulation of Rab geranylgeranylation by the receptor. J Biol Chem. 2011 Nov 25;286(47):40802-13.
 
Cartier A., Parent A., Labrecque P, Laroche G and Parent JL. WDR36 acts as a scaffold protein tethering a G protein-coupled receptor, Gaq and a phospholipase Cb in a signaling complex. J Cell Sci. 2011 Oct 1;124(Pt 19):3292-304.
 
Phone: (617) 919-2404

Mario Castro Martinez

Program Coordinator, Boston Children's Hospital
Mario graduated with a Bachelor's in Animal Science at the University of California, Davis.
 
He has been the administrative support for Dr. Hla and his lab since 2010. If you want to talk theatre, he's down.
 
Phone: (617) 919-6197

Eric Engelbrecht

Research Assistant, Vascular Biology Program, Boston Children's Hospital
Eric Engelbrecht
I joined the Hla lab in 2014 after graduating from Kenyon College with a B.A. in Molecular Biology. I am interested in determining the epigenomic landscape of aortic endothelial cells from regions of laminar and disturbed flow to discover specific factors that regulate heterogenous phenotypes within a single cell-type.
 
Publication Highlights
Blaho V. A., Galvani S., Engelbrecht E., et al. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature. 2015;523(7560):342–346. doi: 10.1038/nature14462
 
Scott H. Freeburg, Eric Engelbrecht, and Wade H. Powell. Subfunctionalization of paralogous aryl hydrocarbon receptors from the frog Xenopus laevis: Distinct target genes and differential responses to specific agonists in a single cell type. Toxicological Sciences. 2017; 155 (2): 337-347. doi: 10.1093/toxsci/kfw212
 
Phone: (617) 919-2167

Sylvain Galvani

Instructor, Vascular Biology Program, Boston Children's Hospital
Instructor, Harvard Medical School
Sylvain Galvani, Ph.D.
Sylvain received his PhD in pathophysiology from the Paul Sabatier University in 2010 before joining Dr. Timothy Hla in april 2010.
 
His work focuses on the role of S1P and S1P1 in adult arterial endothelium. He is interested in understanding the specific role of S1P carriers in the maintenance of endothelium and subsequent vascular homeostasis.
 
Phone: (617) 919-1483

Yu Hisano

Research Fellow, Vascular Biology Program, Boston Children's Hospital
Research Fellow, Harvard Medical School
Yu Hisano, Ph.D.
Yu received his Ph.D. in Pharmacy from Osaka University in 2010. His work focused on the transporter of lipid mediator, sphingosine 1-phosphate. He embarked on a postdoctoral fellowship at RIKEN, where he developed the genome-editing techniques of zebrafish. He joined the laboratory in 2015 and has been working on novel interacting proteins that modulate the sphingosine 1-phosphate receptor.
 
Publication Highlights
Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N. The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors. Science. 2009;323(5913):524-7.
 
Hisano Y, Kobayashi N, Kawahara A, Yamaguchi A, Nishi T. The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720. Journal of Biological Chemistry. 2011;286(3):1758-66.
 
Hisano Y, Inoue A, Okudaira M, Taimatsu K, Matsumoto H, Kotani H, Ohga R, Aoki J, Kawahara A. Maternal and Zygotic Sphingosine Kinase 2 are Indispensable for Cardiac Development in Zebrafish. Journal of Biological Chemistry. 2015;290(24):14841-51.
 
Phone: (617) 919-2166

Yuichi Inagaki

Visiting Scientist, Boston Children's Hospital
Yuichi Inagaki
I received Ph.D. in pharmaceutical science at the Hokkaido University in 2006. My work focused on the molecular biology of the enzymes and GPCRs regulating sphingolipid signaling. I joined the Hla lab in 2016, and my current research focuses on determining the mechanisms involved in the differential receptor signaling and translocation for the study of biological functions. 
 
Publications Highlights
Komiya, T., Sato, K., Shioya, H., Inagaki, Y., Hagiya, H., Kozaki, R., Imai, M., Takada, Y., Maeda, T., Kurata, H., Kurono, M., Suzuki, R., Otsuki, K., Habashita, H., Nakade, S. (2013) Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin. Exp. Immunol. 171, 54–62.
 
Inagaki, Y., Mitsutake, S., Igarashi, Y. (2006) Identification of a nuclear localization signal in the retinitis pigmentosa-mutated RP26 protein, ceramide kinase-like protein. Biochem. Biophys. Res. Commun. 343, 982-987.
 
Inagaki, Y., Pham, T.T., Fujiwara, Y., Kohno, T., Osborne, D.A., Igarashi, Y., Tigyi, G., Parrill, A.L. (2005) Sphingosine-1-phosphate analog recognition and selectivity at S1P4 within the endothelial differentiation gene family of receptors. Biochem. J. 389, 187-195.
 
Phone: (617) 919-2166

Andrew Kuo

Research Fellow, Boston Children's Hospital
Research Fellow, Harvard Medical School
Andrew Kuo
Andrew received his Bachelor Degree in Zoology from National Taiwan University. Further, he completed his PhD training in Cell Biology under the laboratory of Dr. William Sessa, where he became interested in lipid metabolism in the vasculature system, particular triglyceride metabolism in the endothelium. His thesis project characterized Lipid Droplets (LD) for the first time in endothelial cells and demonstrated endothelium LD function as a buffer for lipid homeostasis and transport lipids to subendothelial layer.
 
Andrew joined the Hla lab in May, 2017 to continue his postdoctoral training studying sphingolipid biology. His current research interests include understanding S1P compartmentalization and availability in the blood brain barrier and investigating the functions of S1P bound to different chaperones in vitro and in vivo.
 
Publications Highlights
Kuo, A., Lee, M. Y., Sessa, W. C.. Lipid Droplet Biogenesis and Function in the Endothelium. Circ Res. (2017)
 
Jozsef, L., Tashiro, K., Kuo, A., Park, E., Skoura, A., Albinsson, S., Rivera-Molina, F., Harrison, K. D., Iwakiri Y, Toomre D, Sessa WC. Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry. J Biol. Chem. (2014)
 
Harrison, K. D., Park, E., Gao, N., Kuo, A., Rush, J. S., Waechter, C. J., Lehrman, M. A. and Sessa, W. C.. NgBR is essential for cellular dolichol synthesis and protein glycosylation. EMBO J. (2011).
 
Phone: (617) 919-2403

Vivian Lee

Research Fellow, Vascular Biology Program, Boston Children's Hospital
Research Fellow, Harvard Medical School
I received my Bachelor's degree in Biochemistry at University of Washington and my PhD in Developmental, Regenerative, and Stem Cell Biology at Washington University in St. Louis with Dr. Bob Mecham. My dissertation focused on the role of mutant extracellular matrix genes in thoracic aortic aneurysm (TAA) development. Specifically, we identified a missense mutation in the lysyl oxidase gene in a family with TAA and introduced this mutation into the mouse genome using CRISPR/Cas9 genome editing technology. We then used this mouse model to understand the molecular mechanism underlying TAA pathogenesis.
 
I joined the Hla Lab in April of 2018 to explore the role of S1P signaling in aortic endothelial cell-matrix interaction.
 
Publications Highlights
Lee, V. S., Halabi, C. M., Hoffman, E. P., Carmichael, N., Leshchiner, I., Lian, C. G., Bierhals, A. J., Vuzman, D., Brigham Genomic, M., Mecham, R. P., Frank, N. Y., and Stitziel, N. O. (2016). Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci U S A, 113(31), 8759-8764. 
 
Halabi, C. M., Broekelmann, T. J., Lin, M., Lee, V. S., Chu, M. L., and Mecham, R. P. (2017). Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries. Sci Adv, 3(5), e1602532. 
 
Lee, V., McMahan, R. S., Hu, X., Gao, X., Faustman, E. M., Griffith, W. C., Kavanagh, T. J., Eaton, D. L., McGuire, J. K., and Parks, W. C. (2015). Amphiphilic polymer-coated CdSe/ZnS quantum dots induce pro-inflammatory cytokine expression in mouse lung epithelial cells and macrophages. Nanotoxicology, 9(3), 336-343.
 
Phone: (617) 919-2404

Michel Levesque

Research Fellow, Vascular Biology Program, Boston Children's Hospital
Research Fellow, Harvard Medical School
Michel Levesque, Ph.D.
The focus of my research as a graduate student was the application of a molecular tool for gene targeting, previously engineered in the laboratory of my PhD mentor, Dr. Jean-Pierre Perreault. More precisely, I have used highly specific ribozymes to block gene expression and the replication of two different RNA viruses (HCV and HIV). I have also developed an efficient design process to select active ribozymes against genes of interest. Through this work, I have gained experience on working with RNA in different contexts and in the characterization of gene expression in mammalian cells using techniques such as RNAse protection assays, Northern blots and luciferase assays. I have also developed an expertise in gene targeting and nucleic acid based technology design.
 
After I received my PhD, I moved to MSKCC to study, as research fellow, the roles of alternative polyadenylation of genes related to cancer (CD47 and PTEN). I have used protein (GFP fusion and immunofluorescence) and mRNA (FISH) localisation to assess the role of short and long 3’UTR isoforms. I have also developed western blot and immunoprecipitation conditions to evaluate the isoforms expression and post-translational modifications of a key element of the polyadenylation complex (FIP1L1).
 
Then I moved to Weill Cornell Medicine to work with Dr. Timothy Hla. My research has been focusing on developing a method to study gene expression profile in mouse aortic endothelial cells. Specifically, I have been trying to use the S1PR1 GFP signaling mice model to collect separately endothelial cells exposed to laminar shear stress and disturbed blood flow to characterize their transcriptome. I have also started a project focusing on the transcriptional regulation of S1PR1.
 
Publication Highlights
Lévesque MV, Lévesque D, Brière FP, Perreault J-P. (2010) Investigating a New Generation of Ribozymes in Order to Target HCV. PLoS One 5: e9627. PMID: 20224783
 
Lévesque MV, Perreault J-P. (2012) Target Induced SOFA-HDV Ribozyme. Methods Mol Biol. 848:369-84 PMID: 22315081
 
Scarborough RJ, Lévesque MV, Boudrias-Dalle E, Chute IC, Daniels SM, Ouellette RJ, Perreault JP, and Gatignol A. (2014) A conserved target site in HIV-1 Gag RNA is accessible to both HDV Ribozyme and short hairpin RNA activities. Mol Ther Nucleic Acids. 3:e178 PMID: 25072692
 
Phone: (617) 919-2167

Takahiro Seno

Research Fellow, Vascular Biology Program, Boston Children's Hospital
Research Fellow, Harvard Medical School
Takahiro Seno
I am a clinical immunologist, specializing in rheumatology, allergology and respiratory medicine. I worked as a specialist physician and assistant professor at Kyoto Prefectural University of Medicine, Japan.
 
I did my PhD-training in Dr. Yutaka Kawahito's lab (Department of Inflammation and Immunology) at Kyoto Prefectural University of Medicine, Japan. I was trained in vascular inflammation and lipid metabolism with rheumatic diseases. After receiving my medical doctoral degree, I engaged in research about vascular inflammation, interstitial pneumonitis and development of peptide biomarkers of rheumatoid arthritis.
 
I joined Dr. Tim Hla’s lab in July 2017. In this lab, I investigate the role of S1PR1 and S1PR4 in polymorphonuclear (PMN) cells NETosis. NETs is involved in many diseases, such as systemic lupus erythematous, rheumatoid arthritis, ANCA-associated vasculitis, atherosclerosis, cancer and diabetes mellitus, that have so many clinical unmet needs. Our findings may contribute to resolve the unmet needs. And I also explore the role of ApoM-Fc as a potential therapeutic in anaphylaxis. This findings reveal how S1PRs regulate circulatory collapse, and may be new therapeutic target for the broad range of clinical settings with circulatory collapse.
 

Steven Swendeman

Research Associate, Vascular Biology Program, Boston Children's Hospital
Research Associate, Harvard Medical School
Steven Swendeman, Ph.D.
I am currently investigating the role of the HDL-associated lipid-chaperone, Apolipoprotein M, in vascular function and physiology in normal homeostasis and in human diseases. I did my PhD in Immunology at the Tufts University School of Medicine and Post-doctoral fellowships in Human Genetics at the Whitehead Institute at MIT and in Oncology at the Memorial Sloan-Kettering Cancer Center.  I did further research in Vascular Biology at Weill-Cornell Medical College and The Hospital for Special Surgery.
 
Publication Highlights
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 Dec 22;1(21):e87058. doi: 10.1172/jci.insight.87058.
 
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 Jun;30(6):2351-9. doi: 10.1096/fj.201500064. Epub 2016 Mar 8.
 
Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD, Hla T. HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal. 2015 Aug 11;8(389):ra79. doi: 10.1126/scisignal.aaa2581.
 
Phone: (617) 919-2166

Keisuke Yanagida

Research Fellow, Vascular Biology Program, Boston Children’s Hospital
Research Fellow, Harvard Medical School
Keisuke Yanagida, Ph.D.
Current interest: Role of S1P signaling system in neurovascular homeostasis and diseases, as well as, collective behavior of vascular endothelial cells in angiogenesis.
 
Education and training/employment
2010: PhD (Medicine, The University of Tokyo, PhD-MD course)
2010-2012: Assistant professor (The University of Tokyo)
2013: MD (The University of Tokyo)
Joined Hla lab in 2014 (supported from the Japan Society for the Promotion of Science)
 
Publication Highlights
Yanagida K., Hla T. (2017) Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. Ann. Rev. Physiol. 79
 
Phone: (617) 919-1483