Research Interests
Projects in the Laboratory
The BMPs are multifactorial growth factors that are part of the transforming growth factor (TGF) beta superfamily of growth factors. They were initially identified as bone-inducing factors, hence their name, but are now recognized as important factors in embryogenesis, organ formation and tissue differentiation.
In the vasculature, BMPs respond to normal stimuli to ensure correct vascular formation and coordination with organ-specific elements. The BMPs also react to pathological conditions, such as diabetes and high cholesterol. BMP signaling has been implicated in disorders such as vascular calcification, a common complication of atherosclerosis, as well as vascular malformations. The BMPs exert their effects through cell surface receptors and transcription factors and are modulated by a number of extracellular inhibitors such as matrix Gla protein (MGP). We use a number of mouse models and tissue culture models to study the BMP signaling in the vasculature. We have several lines of investigation ongoing in our laboratory. The projects are related but the emphasis on particular studies may vary with time.
MGP functions as a BMP inhibitor and a protector of elastin. It is highly expressed in the vascular endothelium. Loss of MGP causes vascular calcification in the elastic arteries, which involves endothelial-mesenchymal transition of the endothelial cells. Our goal is to understand the mechanism of BMP and MGP in vascular calcification, atherosclerosis, and diabetic vascular disease.
See e.g. publication:
CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification.
Zhao Y, Yang Y, Wu X, Zhang L, Cai X, Ji J, Chen S, Vera A, Boström KI, Yao Y. JCI Insight, 9(5):e176065, 2024.
Shifting osteogenesis in vascular calcification.
Yao J, Wu X, Qiao X, Zhang D, Zhang L, Ma JA, Cai X, Boström KI, Yao Y. JCI Insight. 6(10):e143023, 2021.
BMP4 and BMP9, their receptors and inhibitors act together to ensure correct differentiation and patterning in the vascular system. Mutations or deletions in several of these genes are known to cause malformations such as AVMs. Our project focuses on the role of the BMP components in AVMs, using relevant mouse and cell models. In addition, we have used mathematical models to help formulate fundamental principles based on what we observe in our experiments.
See e.g. publication:
Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.
Guihard PJ, Guo Y, Wu X, Zhang L, Yao J, Jumabay M, Yao Y, Garfinkel A, Boström KI. Circulation Research. 127(10):1288-1305, 2020.
Elevated endothelial Sox2 causes lumen disruption and cerebral arteriovenous malformations.
Yao J, Wu X, Zhang D, Wang L, Zhang L, Reynolds EX, Hernandez C, Boström KI, Yao Y. J Clin Invest. 129(8):3121-3133, 2019.
We are investigating the links between the vasculature and the development of fibrosis in the lungs, adipose tissue, aorta, and other organs. We are especially interested in the role of the BMPs and MGP in progenitor populations and how differentiation is diverted from normal cell differentiation towards fibrogenesis.
See e.g. publication:
Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis.
Wu X, Zhang D, Qiao X, Zhang L, Cai X, Ji J, Ma JA, Zhao Y, Belperio JA, Boström KI, Yao Y. Eur Respir J. 61(6):2201799, 2023.
Two-step regulation by matrix Gla protein in brown adipose cell differentiation.
Zhang L, Cai X, Ma F, Qiao X, Ji J, Ma JA, Vergnes L, Zhao Y, Yao Y, Wu X, Boström KI. Mol Metab. 80:101870, 2024.
Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor.
Yao J, Ma F, Zhang L, Zhu C, Jumabay M, Yao Z, Wang L, Cai X, Zhang D, Qiao X, Shivkumar K, Pellegrini M, Yao Y, Wu X, Boström KI.Stem Cells, 40(10):932-948, 2022.