Research – Lien Lab

1. Molecular mechanisms of cardiac lymphatic vessel formation during heart development and regeneration.

Lymphatics (Image courtesy of the Lien Lab)

Cardiac lymphatic vessels form along the coronary arteries in fish hearts, similar to those in human hearts. Lymphatic vessels regulate interstitial fluids and modulate immune cell responses. Hearts with defective cardiac lymphatic vessels fail to regenerate. How do coronary vessels guide cardiac lymphatic vessel formation? How does the gene expression network control cardiac lymphatic vessel differentiation from progenitor cells? Can new lymphatic vessel formation help prevent complications after surgical procedures? Using single cell multiomic analyses and creating zebrafish CRISPR mutants, we aim to determine the mechanisms of cardiac lymphatic vessel formation and identify potential therapeutical targets.

Travisano SI, Harrison MR, Thornton ME, Grubbs BH, Quertermous T, and Lien CL. Single nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries in the epicardium. Cell Rep. 42(9): 113106 (2023). PMID: 37676760.

Harrison MR, Feng X, Mo G, Aguayo A, Villafuerte J, Yoshida T, Pearson CA, Schulte-Merker S, and Lien CL. Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration. eLife. E42762 (2019). PMID: 31702553; PMCID: PMC6881116.

2. Molecular mechanisms of coronary vessel formation during heart development and regeneration.

Wild-type coronary vessels (Image courtesy of the Lien Lab)

Interruption of the coronary blood supply severely impairs heart function with often fatal consequences for heart disease patients. The molecular mechanisms of coronary vessel development and revascularization are still not fully understood. We discovered that Cxcl12-Cxcr4 chemokine signaling plays an essential role in coronary vessel formation. How do different vascular cells affect cardiomyocytes and heart development and regeneration? Combining single cell sequencing and zebrafish CRISPR mutants, we aim to elucidate the mechanisms of coronary vessel formation and to understand the intimate interactions between vessels and cardiomyocytes.

Kapuria S, Bai H, Fierros J, Huang Y, Ma F, Yoshida Y, Aguayo A, Kok F, Wiens KM, Pellegrini M, Nagashima M, Hitchcock PF, Yip JK, McCain ML, Lawson ND, Harrison MRH, and Lien CL. Heterogeneous pdgfrb+ cells regulate coronary vessel development and revascularization during heart regeneration in zebrafish. Development 149 (4) dev:199752 (2022). PMID:35088848, PMCID: PMC8918812

Yip JK, Harrison MR, Petersen AP, Villafuerte J, Fernandez EG, Lien CL*, and McCain ML*. Extended culture and imaging of normal and regenerating adult zebrafish hearts in a fluidic device. Lab-on-a-CHIP. 20 (2) 274-84 (2020). PMID: 31872200. * Co-Corresponding.

Harrison MR, Bussmann J, Huang Y, Zhao L, Osorio A, Burns CG, Burns CE, Sucov HM, Siekmann A and Lien CL. Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish. Dev Cell 33, 442-54 (2015). PMIC: 26017769; PMCID: PMC4448080.