Research Themes

Biomaterials and Regenerative Medicine
Molecular and Cellular Engineering

Education

PhD (biochemistry), University of Helsinki, Finland, 1999
Master of Medicine, Tongji Medical University, China, 1990

Research Interests

• Ectopic calcification
• Cell differentiation and phenotype modulation
• Gene targeting
• Tissue Engineering

Contact Information

Department of Bioengineering
University of Washington
Box 355061
William H. Foege Building, Room N310D
Phone: 206-543-3983
Fax: 206-685.3300
E-mail

Research Description

Ectopic calcification is the primary mode of failure of bioprosthetic valves and breast implants.  It is also a common complication of blood vessels occurring in the most popular diseases such as atherosclerosis, diabetes mellitus, and chronic renal disease.  Recently, ectopic calcification has been considered as an actively regulated process that resembles embryonic bone development and remodeling.  My research focuses on the mechanistic studies of ectopic calcification aiming at creating therapeutic strategies to prevent it from developing in blood vessels, cardiac valves, and implanted biomaterials.  Our recent finding that smooth muscle cells undergo lineage reprogramming toward osteochondrogenesis in calcifying vasculature and our identification of early regulatory molecules have made this goal feasible.

Current projects includes: 1) identifying cell origins and molecules regulating ectopic calcification in type II diabetic vasculature using gene targeting and tracing strategies in mouse, 2) exploring mechanisms/pathways involving in the adaptation of body to an ectopic calcifying micro-environment via a state-of-the-art technology, immuno-laser capture microdissection of cells of given differentiation state for gene expression profiling, 3) exploring potential regulatory factors of ectopic calcification and their clinical application via in vitro genetic manipulation, conditional knockout in vivo, and local intervention of the genetic targets.

Honors, Awards and Professional Activities

• 2007 –2012: NIH/NIDDK K01 Research Career Development Award
• 2002 –2004: NIH Cardiovascular Research Training Grant

Selected Publications

• 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  In press
• Leskinen MJ, Heikkilä HM, Speer MY, Hakala JK, Laine M, Kovanen PT, Lindstedt KA:  Mast cell chymase induces smooth muscle cell apoptosis by disrupting NFkB-mediated survival signaling.  Exp Cell Res  2006;312(8):1289-1298
• 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
• Rattazzi M, Bennett BJ, Bea F, Kirk EA, Ricks JL, Polinsky P, Speer MY, Giachelli CM, Schwartz SM, Rosenfeld ME:  Calcification of advanced atherosclerotic lesions in the innominate arteries of Apo E deficient mice: potential role of osteogenic cells.  Arterioscler Thromb Vasc Biol  2005;25:1 - 7
• 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 (Review)
• Speer MY and Giachelli CM:  Regulation of cardiovascular calcification.  Cardiovas Pathol  2004;12(3):63-70 (Review)
• 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
• Speer MY, McKee MD, Robert E. Guldberg, 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
• 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
• 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, 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-b1-dependent and -independent effects.  Arterioscler Thromb Vasc Biol  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-b1 signaling upon stimulation of rat serosal mast cells: a novel function for chymase. FASEB J  2001;15:1377-1388
• 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