Brian W. Wong, Ph.D.

Assistant Professor
Surgery
General Surgery

Developmental, Regenerative and Stem Cell Biology Program
Immunology Program
Biochemistry, Biophysics, and Structural Biology Program
Molecular Genetics and Genomics Program

  • brian.wong@wustl.edu

  • The overarching goal of my research is to understand the role of cellular metabolic pathways in the context of epigenetic modifications in lymphatic endothelial cells

Research Abstract:

The overarching goal of my research is to understand the role of cellular metabolic pathways in the context of epigenetic modifications in lymphatic endothelial cells. My laboratory uses a combination of metabolic profiling and genome-wide methods to uncover key pathways and alterations that regulate cell differentiation, phenotype and function in development, health and disease. We combine in vitro genetic and pharmacological modulation of metabolic and epigenetic pathways with functional phenotyping of cellular functions such as maintenance of barrier function, migration and cell proliferation to determine the contribution of these pathways in physiological and pathological conditions. Our close collaborations with clinicians at the Barnes-Jewish Hospital facilitate the study of metabolic and epigenetic properties in diseased patient tissue samples. Together, we aim to gain basic mechanistic insights of the role of metabolism in lymphangiogenesis.

My laboratory currently employs a skilled microsurgeon, who has expertise in mouse models of heterotopic cardiac transplantation, orthotopic lung transplantation and heterotopic kidney transplantation in mice and rats. We leverage this expertise to study the efficacy of "metabolic modulation" therapies in preventing chronic allograft rejection. Of particular interest is our study of the role of lymphatics in the regulation of transplant immunobiology and tolerance. Further, we utilize transgenic models with lymphatic-specific deletion of key metabolic and epigenetic genes to demonstrate a role of lymphatic metabolism in the context of solid organ allograft rejection. The
overall goal is to better understand developmental and physiological processes to effectively translate these concepts into potential preventatives or therapeutics.

1. Vascular and lymphatic endothelial cell metabolism
Despite promising results from pre-clinical animal models, anti-growth factor-targeted antiangiogenic therapies, particularly in the context of cancer, have failed to yield significant improvements in overall survival when tested clinically in humans. During my postdoctoral training under the mentorship of Dr. Peter Carmeliet at the Center for Cancer Biology at the KU Leuven, Leuven, Belgium, I focused on elucidating the role of metabolic pathways on the regulation of angiogenesis and lymphangiogenesis. In our current work, we are extending our research in this
area to better understand epigenetic gene expression mechanisms that may be controlled by modulation of cellular metabolic pathways in the context of health and disease.

2. Study of transplantation, cardiac allograft vasculopathy and atherosclerosis Allograft vasculopathy is the leading cause of solid organ transplant rejection one-year posttransplantation. I completed my doctoral training under the mentorship of Dr. Bruce McManus at the Centre for Heart Lung Innovation at the University of British Columbia, Vancouver, Canada, where I focused on the role of VEGF family members on alterations in endothelial permeability to low-density lipoproteins in the context of cardiac allograft vasculopathy, and other atherosclerotic diseases (native atherosclerosis and diabetes mellitus with atherosclerosis). Further, as cardiac allograft vasculopathy presents as an accelerated form of atherosclerosis, I have also studied native atherosclerosis in both mouse models and human tissue samples. In our current work, we plan to continue our investigation into mechanisms of allograft rejection.

3. Study of cardiovascular disease and other inflammatory conditions Complementing my doctoral work, I also engaged in collaborations with both academia and industry, focused on coxsackievirus-induced dilated cardiomyopathy, mouse models of atherosclerosis and testing novel small-molecule inhibitors in the context of transplant rejection. Previous experience in interacting with industry to successfully complete drug screening of
compounds provides the knowledgebase to continue these types of interactions in the future.

Selected Publications:

Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Bruning U, Scheinok S, Treps L, Cantelmo AR, Dubois C, de Zeeuw P, Goveia J, Zecchin A, Taverna F, Morales-Rodriguez F, Brajic A, Conradi LC, Schoors S, Harjes U, Vriens K, Pilz GA, Chen R, Cubbon R, Thienpont B, Cruys B, Wong BW, Ghesquiere B, Dewerchin M, De Bock K, Sagaert X, Jessberger S, Jones EAV, Gallez B, Lambrechts D, Mazzone M, Eelen G, Li X, Fendt SM, Carmeliet P. Quiescent endothelial cells upregulate fatty acid β-oxidation for vasculoprotection via redox homeostasis. Cell Metab. 2018; 28: 881-894. [Impact factor 20.565; Cited by 1] PMID: 30146488; PMCID: N/A

Zecchin A*, Wong BW*, Tembuyser B, Souffreau J, Van Nuffelen A, Wyns S, Vinckier S, Carmeliet P, Dewerchin M. Live imaging reveals a conserved role of fatty acid β-oxidation in early lymphatic development in zebrafish. Biochem Biophys Res Commun. 2018; 503: 26-31. [Impact factor - 2.559] PMID: 29730294; PMCID: N/A

Wong BW, Zecchin A, Garcia-Caballero M, Carmeliet P. Developmental aspects of lymphangiogenesis: Emerging
focus on novel regulators and organ-specific function. Dev Cell. 2018; 45: 289-301. Review. [Impact factor - 9.616;
Cited by 1] PMID: 29738709; PMCID: N/A

Eelen G, de Zeeuw P, Treps L, Harjes U, Wong BW, Carmeliet P. Endothelial cell metabolism. Physiol Rev. 2018;
98: 3-58. Review. [Impact factor - 24.014; Cited by 20] PMID: 29167330; PMCID: PMC5866357

Last Updated: 8/14/2019 1:53:25 PM

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