Kristina I Bostrom, M.D., Ph.D.
Research Interests
The overall goal of our laboratory is to understand the role of bone morphogenetic proteins (BMPs), and their inhibitors and receptors in vascular disease such as atherosclerosis, vascular calcification, diabetic vascular disease and arteriovenous malformations (AVMs). We have identified a regulatory pathway, in which BMP-2/4 induces the expression of activin-like kinase receptor 1 (ALK1), a receptor for BMP-9. ALK1 is essential for angiogenesis and regulates expression of vascular endothelial growth factor (VEGF) and BMP-inhibitors including matrix Gla protein (MGP). We have found that this regulatory pathway is affected in vascular disease and appears to be essential for vascular homeostasis. We have also established a source of cardiovascular precursor cells for use in our studies, so-called de-differentiated fat (DFAT) cells, derived from white mature adipocytes. Our current projects focus on (1) how MGP prevents vascular calcification, (2) the role of BMP-signaling in diabetic vascular disease, (3) the mechanism of AVMs, (4) how DFAT cells differentiate into cardiovascular cells, and (5) biological patterns involving BMP and MGP.
Yao Yucheng, Jumabay Medet, Ly Albert, Radparvar Melina, Wang Anthony H, Abdmaulen Raushan, Boström Kristina I Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood. 2012; 119(21): 5037-47.
Boström Kristina I, Garfinkel Alan, Yao Yucheng, Jumabay Medet Concise review: applying stem cell biology to vascular structures. Stem cells (Dayton, Ohio). 2012; 30(3): 386-91.
Yao Yucheng, Jumabay Medet, Wang Anthony, Boström Kristina I Matrix Gla protein deficiency causes arteriovenous malformations in mice. The Journal of clinical investigation. 2011; 121(8): 2993-3004.
Boström Kristina I, Rajamannan Nalini M, Towler Dwight A The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circulation research. 2011; 109(5): 564-77.
Boström Kristina I, Jumabay Medet, Matveyenko Aleksey, Nicholas Susanne B, Yao Yucheng Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circulation research. 2011; 108(4): 446-57.
Yao Y, Bennett BJ, Wang X, Rosenfeld ME, Giachelli C, Lusis AJ, Bostrom KI Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification. Circulation Research 2010; .
Jumabay M, Zhang R, Yao Y, Goldhaber JI, Bostrom KI Spontaneously beating cardiomyocytes dervied from white mature adiopocytes . Cardiovascular Research 2010; 85: 17-27.
Shao ES, Lin L, Yao Y, Bostrom KI Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells . Blood 2009; 114: 2197-2206.
Yao Y, Shahbazian A, Bostrom KI Proline and gamma-carboxylated glutamate residues in Matrix GLA protein are critical for binding of bone morphogenetic protein-4. Circulation Research 2008; 102: 1065-1074.
Yao, Y. Nowak, S. Yochelis, A. Garfinkel, A. Bostrom, K. I. Matrix GLA protein, an inhibitory morphogen in pulmonary vascular development. J Biol Chem. 2007; 282(41): 30131-42.
Garfinkel, A. Tintut, Y. Petrasek, D. Bostrom, K. Demer, L. L. Pattern formation by vascular mesenchymal cells. Proc Natl Acad Sci U S A. 2004; 101(25): 9247-50.