Cecilia Giachelli, Ph.D.

UNIVERSITY OF WASHINGTON

Primary Research:

The major goals of Dr. Giachelli's lab are to develop molecular and cellular bioengineering approaches to prevent and treat ectopic calcification and promote healing, biocompatibility, tissue regeneration and biomineralization. Dr. Giachelli has been working in the area of vascular calcification for over 15 years. Her early discovery of the bone protein, osteopontin, in calcified valves and atherosclerotic plaques contributed to our current understanding of vascular calcification as an active, cell-mediated process. Building on these findings, her lab discovered the anticalcific functions of osteopontin in the vasculature, including its role in blocking calcium phosphate crystal formation and promoting cellular resorption. Her lab has published on important in vitro and in vivo models for vascular calcification, including those for arterial medial (MGP-/-mice; chronic kidney disease mice) and intimal calcification (fat fed LDLR-/- mice; ApoE-/- mice). Her studies were among the first to identify elevated phosphate as a major stimulus for smooth muscle cell calcification, and contributed to the “phosphate hypothesis” of vascular calcification in chronic kidney disease. Her research has identified an important role of role of sodium-dependent phosphate transporters in vascular calcification. Dr. Giachelli has developed floxed PiT-1, PiT-2 and Runx2 mice and is currently using these mice to investigate cell-mediated mechanisms of vascular calcification in the setting of atherosclerosis, chronic kidney disease, diabetes and calcific aortic valve disease. During the process of creating these mutant mice for disease-related studies, we also discovered previously unknown, critical roles in development that are also pursued in the lab. The lab currently focuses on mechanistic studies aimed at developing novel therapeutic targets and innovative approaches for treating and preventing ectopic calcification in disease, traumatic injury, and medical devices.

To learn more about Dr. Giachelli and her work, visit the lab website at https://catalyst.uw.edu/workspace/ceci/13984/76132

Recent Publications:

1. Lin ME, Chen T, Leaf EM, Speer MY, Giachelli CM. Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice. American Journal of Pathology. 2015 Jul;185(7):1958-69.
2. Chavkin NW, Jun Chia J, Crouthamel MH, Giachelli CM. Phosphate uptake-independent signaling functions of the type III sodium-dependent phosphate transporter, PiT-1, in vascular smooth muscle cells. Exp Cell Res. 2015 Feb; 333(1):39-48.
3. Paloian NJ and Giachelli CM. A current understanding of vascular calcification in CKD. Am K Physiol Renal Physiol. 2014 Oct; 307(8):F891-900.
4. Wallingford MC and Giachelli CM. Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm. Mech Dev. 2014 Aug; 133:189-202.
5. Tung JC, Paige SL, Ratner BD, Murry CE, Giachelli CM. Engineered biomaterials control differentiation and proliferation of human-embryonic-stem-cell-derived cardiomyocytes via timed Notch activation. Stem Cell Reports. 2014 Feb 27;2(3):271-81.
6. Rementer CW, Wu M, Buranaphatthana W, Yang HY, Scatena M, Giachelli CM. An inducible, ligand-independent receptor activator of NF-κB gene to control osteoclast differentiation from monocytic precursors. PLoS One. 2013 Dec 27; 8(12):e84465.
7. Crouthamel M, Lau WL, Leaf EM, Chavkin NW, Wallingford MC, Peterson DF, Li X, Liu Y, Chin MT, Levi M, Giachelli CM. Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2. Arterioscler Thromb Vasc Biol. 2013 11:2625-32
8. Lau WL, Linnes M, Chu EY, Foster BL, Bartley BA, Somerman MJ, Giachelli CM. High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease. Nephrol Dial Transplant. 2013 Jan;28(1):62-9.
9. Lau WL, Leaf EM, Hu MC, Takeno MM, Kuro-o M, Moe OW, Giachelli CM. Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int. 2012 Dec;82(12):1261-70.
10. Naik V, Leaf E, Yang H-Y, Giachelli CM, and Speer MY: Contribution of smooth muscle cells to vascular cartilaginous metaplasia and calcification in atherosclerotic mouse vessels: an in vivo genetic fate mapping study. Cardiovasc Res. 2012 Jun 1;94(3):545-54. doi: 10.1093/cvr/cvs126. Epub 2012 Mar 21
11. Pai A, Leaf EM, El-Abbadi M, Giachelli CM. Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. Am J Pathol. 2011 Feb;178(2):764-73.
12. 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 Jul 1;110(4):935-47.
13. Speer MY, Yang HY, Look A, Frutkin A, Dichek D, Giachelli CM. Smooth Muscle Cells Give Rise to Osteochondrogenic Precursors and Chondrocytes in Calcifying Arteries, Circulation Research 104(6):733-41, 2009
14. El-Abbadi MM, Pai AS, Leaf EM, Yang HY, Bartley BA, Quan KK, Ingalls CM, Liao HW, Giachelli CM. Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin. Kidney Int. 75(12):1297-307, 2009.

Recent Presentations:

1. Vascular Calcification: New Concepts in Regulation and Therapy. International Vascular Biology Meeting, April 15, 2014, Kyoto, Japan
2. Vascular Consequences of Elevated Phosphate. American Society for Nephrology, Kidney Week 2014, Philadelphia, PA November 15, 2014
3. The Role of Calcium and Phosphate in Vascular Disease in the Setting of Chronic Kidney Disease. American Society of Hypertension, New York, New York, May 16, 2015
4. Changes in cell lineage: SMC to osteoblast, Vasculata, July 2014, Seattle, WA

Lab Members:

Faculty
Mei Yanfeng Speer (Research Associate Professor, Bioengineering)

Staff
Elizabeth Soberg (Lab Manager and Research Scientist)
Mandy Lund (Research Scientist)

Postdoctoral Fellows
Melissa Jackson (Bioengineering)
Mary Wallingford (Bioengineering)
Shunsuke Yamada (Bioengineering)

Graduate Students
Worakanya Buranaphatthana (Oral Health Sciences)
Nicholas Chavkin (Bionengineering)
Theodore Chen (Bioengineering)
Jia Jun Chia (Bioengineering)
Karen Eaton (Bioengineering)
Cameron Rementer (Bioengineering)

Undergraduate Students
Kadin Brooks (Bioengineering)
Jenna Kita (Biology)
Anastasia Bernhard (Microbiology)

Laboratory Motto:
"Make sure it’s in the linear range and always have a negative and positive control!"

Laboratory Mascot:
"Penguin"