Dr. Long’s lab is mainly interested in the molecular underpinnings of vascular smooth muscle (VSMC) phenotypic plasticity, which underlies a variety of prominent vascular diseases. Her expertise relates to the utilization of RNA/DNA deep sequencing, bioinformatics, molecular biology, and translational vascular disease models (arterial venous fistula, wire injury, and aortic aneurysm) to discover and dissect novel regulators in different vascular disorders. She has a long-standing interest in regulation of novel long noncoding RNAs (lncRNAs) and coding genes in vascular smooth muscle pathophysiology.
Role of lncRNAs in the regulation of VSMC phenotype and vascular disease
Dr. Long’s lab has recently identified a novel MKL1-associated Inflammatory Long Noncoding
RNA named KILN. Initial studies showed that KILN is highly induced by proinflammatory
stimuli, physically interacts with Myocardin related transcription factor A (MRTFA,
aka MKL1), and positively regulates the gene expression of IL8, a closely neighboring
gene. These exciting findings serve as the basis for ongoing projects that will dissect
the interplay between KILN, MKL1, and IL8 in aortic aneurysm and arterial aging using
humanized mouse models.
Tetraspanin and Integrin signaling in vascular smooth muscle phenotypic modulation and vascular remodeling
This project relates to a novel transmembrane protein, TSPAN2, which is intimately
associated and promotes VSMC differentiation. Current focus is to dissect the transcriptional
regulation of Tspan2 gene expression in VSMCs using CRISPR/CAS genome editing, and
elucidate how TSPAN2 signals through CD44 and ITGA3, two opposing signaling pathways
in arterial venous fistula (AVF) remodeling and atherosclerosis progression using
VSMC-specific knockout mouse models.
Regulation of arterial venous fistula (AVF) maturation
Patients with end-stage renal disease (ESRD) rely on hemodialysis, which requires
a functional high-flow vascular access preferably achieved through an AVF conduit.
Inadequate venous 
maturation is one major determinant of AVF failure but the underlying mechanism is
poorly understood. Dr. Long’s lab has recently perfected two different AVF mouse models
recapitulating the human AVF process. Using state-of-the-art genetic tools, including
lineage tracing mouse strains, tissue-specific inducible knockout mice in conjunction
with translational human AVF samples, her lab has demonstrated, for the first time,
a unique dual function of mature VSMCs in venous maturation and neointimal hyperplasia
during AVF remodeling. Currently her lab is actively investigating VSMC origin(s)
and key pathways required to AVF maturation using single cell RNA-seq and novel VSMC
lineage tracing mouse models.
Making veins stronger so heart bypass grafts, dialysis access work better
Mitogen-Activated Protein Kinase 14 is a Novel Negative Regulatory Switch for the Vascular Smooth Muscle Cell Contractile Gene Program
Xiochun long, Sarah L. Cowan, and Joseph M. Miano
Originally published 21 Nov 2012 | https://doi.org/10.1161/ATVBAHA.112.300645 |Arteriosclerosis, Thrombosis, and Vascular Biology: 2013;33-378-386
INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10. bioRxiv. 2023 Jan 9:2023.01.07.522948. doi: 10.1101/2023.01.07.522948. Preprint.PMID: 36711681
Generation and Comparative Analysis of an Itga8-CreER T2 Mouse with Preferential Activity in Vascular Smooth Muscle Cells. Nat Cardiovasc Res. 2022 Nov;1(11):1084-1100. doi: 10.1038/s44161-022-00162-1. Epub 2022 Nov 11.PMID: 36424917
Correction to: Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodelling. Cardiovasc Res. 2022 Feb 7:cvac011. doi: 10.1093/cvr/cvac011. Online ahead of print.PMID: 35137003
