Yanfeng (Mei) Speer

Research Associate Professor

yfwang@u.washington.edu
Phone: (206)543-3983
Office: Foege N310D

UW Bioengineering faculty Yanfeng Mei Speer

Lab Website
How I am inventing the future of medicine
My long-term scientific goal is to translate the mechanistic studies of cardiovascular disease in the laboratory into clinical research in areas of inflammation, atherosclerosis, and diabetes mellitus, aiming to develop testing beds and innovative prophylactic/therapeutic strategies via genetic engineering approaches.
Research Interests
Type II diabetes mellitus
Atherosclerosis
Vascular and valvular calcification
Cell differentiation and lineage reprogramming
Gene targeting
Research Description
Diabetes mellitus is a well-recognized killer, affecting an estimated 25.8 million people and has been the 6th – 7th leading cause of death in the US since year 2002. Type II diabetes mellitus (T2DM) is the most common form of this disease, accounting for 90 – 95% of the cases. While type I diabetes mellitus and T2DM have different etiology, the long-term complications are very similar, leading to life-threatening and disabling consequences such as heart disease, stroke, renal failure, and gangrene of lower-limbs. Mechanisms underlying the development of these complications are not yet well-understood; however, blood vessels and cardiac valves of T2DM patients are atherosclerotic, featured with lipid accumulation, increased amount of disorganized connective tissue, deposition of calcium-phosphate salts, and development of cartilaginous metaplasia and bone-like structures. Recent years, with the application of electron beam computed tomography in clinics ectopic calcification in blood vessels and cardiac valves has been identified as an independent predictor for the heightened risk of cardiovascular mortality, stroke, and lower-limb amputation in T2DM. Importantly, according to our previous genetic fate mapping and targeting studies, mural cells of blood vessels and cardiac valves are highly plastic and predisposed to lineage reprogramming towards cartilaginous and bony precursor cells in response to diseased environmental cues, such as T2DM. It is highly likely that differentiation of cardiovascular mural cells towards osteochondrogenic fate is the early course of the events, possible to target for prophylactic and therapeutic purposes.

Current projects includes: 1) to identify cellular and molecular targets associated with cardiovascular calcification in atherosclerosis, diabetes, and diabetic nephropathy through in vitro genetic manipulation, tissue-specific genetic targeting in vivo, and local intervention of the genetic targets, 2) to develop platform for gene targeting and drug screening associated with T2DM cardiovascular complications, 3) to explore whether interference of the identified pathways through antagonists prevents and/or rescues T2DM cardiovascular calcification.

Education
Ph.D., Biochemistry, University of Helsinki, Finland, 1999
Master of Medicine, Tongji Medical University, China, 1990
Postdoc Information
Awards and Honors
2007-2012 NIDDK Research Career Development award, National Institution of Health

2009-2011 New Investigator Award, Diabetes Endocrinology Research Center, University of Washington

2004 Young Investigator Award finalist, The XIIIth International Vascular Biology Meeting, Toronto, Canada

2002-2004 Ruth L. Kirschstein National Research Service Award, administered by NIH HL07828 Cardiovascular Research Training Grant, University of Washington

UW Bioengineering Courses Taught
BIOEN 532 – Graduate Core Seminar, Networking
Selected Publications
Nguyen NB, Naik V, and Speer MY: Diabetes mellitus accelerates cartilaginous metaplasia and calcification in atherosclerotic vessels of LDLr mutant mice. Cardiovasc Path 2013;22:167-175

Naik V, Leaf E, Hu JH, Yang H-Y, Nguyen NB, Giachelli CM, and Speer MY: Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study. Cardiovasc Res 2012;94:545-554

Speer MY: Smooth muscle cells in pathogenesis of vascular medial cartilaginous metaplasia. Cardiovas Res 2011;89:1-2 Invited Editorial

Speer MY, Li X, Hiremath PG, and Giachelli CM: Runx2/Cbfa1, but not loss of myocardin, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis. J Cell Biochem 2010;110:935-947

Li X, Speer MY, Yang H-Y, Bergen J, and Giachelli CM: Vitamin D receptor activators induce an anticalcific paracrine program in macrophages: requirement of osteopontin. Arterioscler Thromb Vasc Biol 2010;30:321-326

Festing MH, Speer MY, Yang H-Y, and Giachelli CM: Generation of mouse conditional and null alleles of type III sodium- dependent phosphate transporter Pit-1. Genesis 2009;47:858-863

Ahmad PJ, Trcka D, Xue S, Speer MY, Giachelli, CM, and Bendeck MP: Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization. Am J Pathol 2009;175:2686-2696

Speer MY, Yang H-Y, Brabb T, Leaf E, Look A, Lin W-L, Frutkin A, Dichek D, and Giachelli CM: Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circulation Research 2009;104:733-741, Featured with accompanying editorial, 112 citations since its inception, 28/year

Speer MY, Chien YC, Quan M, Yang H-Y, Wali H, McKee MD, and Giachelli CM: Smooth muscle cells deficient in osteopontin have enhanced susceptibility to calcification in vitro. Cardiovasc Res 2005;66(2):324 – 333

Giachelli CM, Speer MY, Li X, Rajachar RM, and Yang H: Regulation of vascular calcification: roles of phosphate and osteopontin. Circ Res 2005;96(7):717 – 722 Invited Review, 176 citations since its inception

Speer MY and Giachelli CM: Regulation of cardiovascular calcification. Cardiovas Pathol 2004;12(3):63-70 Invited Review, cited 141 citations since its inception

Latti S, Leskinen M, Shiota N, Wang Y, Kovanen PT, Lindstedt KA: Mast cell-mediated apoptosis of endothelial cells in vitro: A paracrine mechanism involving TNF-alpha-mediated down-regulation of bcl-2 expression. J Cell Physiol 2003;195(1):130-138

Leskinen MJ, Lindstedt KA, Wang Y, Kovanen PT: Mast cell chymase induces SMC apoptosis by a mechanism involving in fibronectin degradation and disruption of focal adhesions. Arterioscler Thromb Vasc Biol 2003;23(2):238-243

Steitz SA, Speer MY, McKee MD, Liaw L, Almeida M. Yang HY, and Giachelli CM: Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am J Pathol 2002;161:2035-2046 247 citations since its inception, 22/year

Speer MY, McKee MD, Guldberg RE, Liaw L, Yang HY, Tung E, Karsenty G, and Giachelli CM: Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 2002;196:1047-1055 203 citations since its inception, 18/year

Steitz SA, Speer MY, Curinga G, Ying-Yang H, Haynes P, Aebersold R, Schinke T, Karsenty G, and Giachelli CM: Smooth muscle cell phenotypic transition associated with calcification: up-regulation of Cbfa-1 and down-regulation of smooth muscle lineage markers. Circ Res 2001;89 (12):1147-1154 373 citations since its inception, 31/year

Wang Y, Shiota N, Leskinen M, Lindstedt KA, and Kovanen PT: Mast cell chymase inhibits smooth muscle cell growth and collagen expression in vitro: transforming growth factor-1-dependent and -independent effects. Arterioscler Thromb Vasc Bio 2001;21 (12):1928-1933

Lindstedt KA, Wang Y, Shiota N, Hyytiinen M, Kokkonen J, Keski-Oja J, and Kovanen PT: Activation of paracrine TGF-1 signaling upon stimulation of rat serosal mast cells: a novel function for chymase. FASEB J 2001;15:1377-1388 124 citations since its inception

Leskinen M, Wang Y, Leszczynski D, Lindstedt KA, and Kovanen PT: Mast cell chymase induces apoptosis of vascular smooch muscle cells. Arterioscler Thromb Vasc Biol 2001;21:516-522

Wang Y and Kovanen PT: Heparin proteoglycans released from rat serosal mast cells inhibit proliferation of rat aortic smooth muscle cells in culture. Circ Res 1999;84:74-83

Wang Y, Lindstedt KA, and Kovanen PT: Phagocytosis of mast cell granule remnant-bound LDL by smooth muscle cells of synthetic phenotype: a scavenger receptor-mediated process that effectively stimulates cytoplasmic cholesteryl ester synthesis. J Lipid Res 1996;37:2155-2166

Wang Y, Lindstedt KA, and Kovanen PT: Mast cell granule remnants carry LDL into smooth muscle cells of the synthetic phenotype and induce their conversion into foam cells. Arterioscler Thromb Vasc Biol 1995;15:801-810

 

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