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The overarching goal of my laboratory is to understand the cellular and molecular processes during vascular remodeling.  My laboratory focuses on understanding pericyte (PC) biology and defining the role of vascular cells, particularly PCs, SMCs and other mural cells, in the pathogenesis of pulmonary arterial hypertension (PAH).  Our ultimate goal is to restore functional vessels and facilitate new avenues of therapeutic targeting in PAH.

PC lineage change and fate mapping in hypoxia-induced pulmonary hypertension(PH) via HIF2a activation PAH is a life-threatening disease characterized by abnormally elevated pulmonary pressures and progressive right heart failure that, if untreated, leads to death within one year of diagnosis. While the etiology of PAH is unknown, muscularized distal arterioles due to excessive proliferation of pulmonary arterial smooth muscle cells (SMCs) is one of the major pathological features of this disorder, which progressively occludes precapillary pulmonary arteries. It is unclear what initiates the growth of PASMCs in PAH vascular lesions. PCs are the mural cells of blood capillaries and regulate homeostasis in the blood-brain barrier, promote tumor metastasis and function in vascular morphogenesis and development. Because of their plasticity, our particular focus in PAH is determining whether PCs can differentiate into vascular SMCs. HIF2a was a key transcriptional factor that regulated SDF-1 expression in pericyte lineage change and contributed to vascular remodeling. In addition, the animals with HIF2a overexpression showed increased cell inflammation and different inflammatory levels may be associated with HIF2a overexpression. We implemented state-of-art technologies including single-cell RNA-seq, lineage tracing, tissue clearing, 3D deep tissue light-sheet imaging, and super high-resolution microscopy to examine lung vasculature and optimized methods to distinguish PCs from other mural cells in both mouse and human samples. We found that PCs 1) differentiate into SMC-like via activated HIF2a/SDF1 signaling, 2) drive impaired vessel remodeling and loss of capillaries and 3) contribute to PAH pathobiology. (This current work is under Major Revision in EMBO Reports, other PMID: 32766264,25447046, 27456128)

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PC marker identification Our study focused on identifying PC-specific markers by analyzing single-cell RNA sequencing data from tissue-specific mouse PC populations generated by the Tabula Muris Senis and human lung cell atlas. We identified potential PC marker candidates, including Kcnk3 (in the lung); Rgs4 (in the heart); Myh11 and Kcna5 (in the kidney); Pcp4l1 (in the bladder); and Higd1b (in the lung and heart). (PMID: 35722109)

Pericytes respond to increased flow induced PH The other significant pathological features of PAH are associated with increased blood flow. Little is known about how endothelial cells, PCs and SMCs impact the pulmonary vascular tone. Our new and innovative study will investigate the consequences of extended pneumonectomy (EP) on mouse pulmonary circulation and the fundamental roles of vascular cells' contribution to vascular remodeling in PH secondary to increased blood flow. Identifying the cell-cell interactions and the activated signaling pathway responsible for developing vascular remodeling could lead to potential therapies. Lastly, EP is also a novel mural model to study lung regeneration, aging and compensatory growth.

Disrupted PC and endothelial cell interactions during vessel remodeling in PAH. PCs isolated from PAH patients' lungs exhibited defective motility and polarity that prevented them from correctly associating with endothelial tubes, leading to fewer endothelial-PC interactions. We also found that PAH PCs have a reduced capacity to associate with pulmonary microvascular endothelial cells (PMVECs) due to endogenous deficiencies in Wnt5a signaling. (PMID: 30586764)


ADAR1 mediated RNA editing in pulmonary mural cells Our study will define the unique and complementary roles of A-to-I RNA editing in SMCs by controlling fundamental pulmonary vascular function and pulmonary hypertension. Adenosine deaminase acting on RNA 1 (ADAR1) catalyzes the conversion of adenosine (A) to inosine (I) in double-stranded RNA (dsRNA), which is critical to prevent auto-inflammatory responses mediated by activation of the type I interferon (IFN) signaling. Such RNA editing is a widespread RNA modification and is linked to numerous physiologic and pathophysiologic conditions of human health, but any biological activity in the pulmonary vasculature has been ignored to date. Notably, the mechanistic, cell type-specific proposed studies garnered by assessment of ADAR1 in smooth muscle contexts constitute key insights that emphasize the crucial role of ADAR1 in PH – insights rarely offered in any biologic context. As such, our work will provide the foundation for the therapeutic targeting of ADAR1 and/or downstream targets IFN in smooth muscle cells in PH. Downregulation of RNA editing will additionally serve as an RNA-based diagnostic or prognostic marker in this deadly PAH.


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Our lab uses the ProOx 360 and A-Chamber from BioSpherix Ltd for providing controlled hypoxic conditions during in vivo vascular experiments. More information can be found at:

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