Yu Ru Shih | Scholars@Duke

Yu Ru Shih
Assistant Professor of Orthopaedic Surgery

Current Research Interests

The long term goal of my research is to develop effective, innovative, and safe treatments for musculoskeletal conditions including fracture, osteoarthritis, bone cancer, and the associated pain. This is achieved by understanding the fundamental biology using animal models, animal/human tissues, and in vitro cultures that involves primary or stem cell-derived models. These understandings form the basis for identification of therapeutic targets to develop treatments that promote tissue repair and pain relief.

Current Appointments & Affiliations

Assistant Professor of Orthopaedic Surgery, Orthopaedics, Orthopaedics 2022

Contact Information

Background
Education, Training, & Certifications
- Ph.D., National Yang Ming University (Taiwan) 2010
Expertise
Subject Headings
Research
Selected Grants
- Modulation of local adenosine signaling to attenuate fracture pain awarded by National Institutes of Health 2021 - 2026
- Adenosine A2B Receptor in Bone Health and Osteoporosis awarded by National Institutes of Health 2017 - 2023
- Bioinspired Synthetic Grafts for Bone Regeneration awarded by National Institutes of Health 2017 - 2019
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Madhurakkat Perikamana, S. K., N. Seale, J. Hoque, J. H. Ryu, V. Kumar, Y. V. Shih, and S. Varghese. “Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.” Advanced Functional Materials 32, no. 4 (January 1, 2022). https://doi.org/10.1002/adfm.202108221.
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  - Newman, Hunter, Yuru Vernon Shih, and Shyni Varghese. “Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.” Biomaterials 277 (October 2021): 121114. https://doi.org/10.1016/j.biomaterials.2021.121114.
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  - Hoque, Jiaul, Yu-Ru V. Shih, Yuze Zeng, Hunter Newman, Nivedita Sangaj, Neha Arjunji, and Shyni Varghese. “Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.” Biomaterials 273 (June 2021): 120819. https://doi.org/10.1016/j.biomaterials.2021.120819.
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  - Moreno, Ana M., Xin Fu, Jie Zhu, Dhruva Katrekar, Yu-Ru V. Shih, John Marlett, Jessica Cabotaje, et al. “In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.” Mol Ther 28, no. 8 (August 5, 2020): 1931. https://doi.org/10.1016/j.ymthe.2020.06.027.
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  - Zeng, Yuze, Yu-Ru V. Shih, Gurpreet S. Baht, and Shyni Varghese. “In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.” Adv Mater 32, no. 8 (February 2020): e1906022. https://doi.org/10.1002/adma.201906022.
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  - Shih, Yu-Ru V., Mengqian Liu, Seong Keun Kwon, Masayuki Iida, Ya Gong, Nivedita Sangaj, and Shyni Varghese. “Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss.” Sci Adv 5, no. 8 (August 2019): eaax1387. https://doi.org/10.1126/sciadv.aax1387.
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  - Shih, Yuru Vernon, and Shyni Varghese. “Tissue engineered bone mimetics to study bone disorders ex vivo: Role of bioinspired materials.” Biomaterials 198 (April 2019): 107–21. https://doi.org/10.1016/j.biomaterials.2018.06.005.
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  - Katrekar, Dhruva, Genghao Chen, Dario Meluzzi, Ashwin Ganesh, Atharv Worlikar, Yu-Ru Shih, Shyni Varghese, and Prashant Mali. “In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.” Nat Methods 16, no. 3 (March 2019): 239–42. https://doi.org/10.1038/s41592-019-0323-0.
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  - Ryu, Ji Hyun, Gyeong Jin Lee, Yu-Ru V. Shih, Tae-Il Kim, and Shyni Varghese. “Phenylboronic Acid-polymers for Biomedical Applications.” Curr Med Chem 26, no. 37 (2019): 6797–6816. https://doi.org/10.2174/0929867325666181008144436.
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  - Liu, Mengqian, Manando Nakasaki, Yu-Ru Vernon Shih, and Shyni Varghese. “Effect of age on biomaterial-mediated in situ bone tissue regeneration.” Acta Biomater 78 (September 15, 2018): 329–40. https://doi.org/10.1016/j.actbio.2018.06.035.
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  - Seale, Nailah, Suvasini Ramaswamy, Yu-Ru Shih, Inder Verma, and Shyni Varghese. “Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.” Transplantation 102, no. 9 (September 2018): e373–81. https://doi.org/10.1097/TP.0000000000002330.
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  - Moreno, Ana M., Xin Fu, Jie Zhu, Dhruva Katrekar, Yu-Ru V. Shih, John Marlett, Jessica Cabotaje, et al. “In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.” Mol Ther 26, no. 7 (July 5, 2018): 1818–27. https://doi.org/10.1016/j.ymthe.2018.04.017.
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  - González Díaz, Eva C., Yu-Ru V. Shih, Manando Nakasaki, Mengqian Liu, and Shyni Varghese. “Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.” Tissue Eng Part A 24, no. 13–14 (July 2018): 1148–56. https://doi.org/10.1089/ten.TEA.2017.0297.
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  - Kang, Heemin, Yu-Ru V. Shih, and Shyni Varghese. “Direct Conversion of Human Pluripotent Stem Cells to Osteoblasts With a Small Molecule.” Curr Protoc Stem Cell Biol 44 (February 28, 2018): 1F.21.1-1F.21.6. https://doi.org/10.1002/cpsc.44.
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  - Shih, Yu-Ru, Heemin Kang, Vikram Rao, Yu-Jui Chiu, Seong Keun Kwon, and Shyni Varghese. “In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.” Proc Natl Acad Sci U S A 114, no. 21 (May 23, 2017): 5419–24. https://doi.org/10.1073/pnas.1702576114.
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  - Kang, Heemin, Yu-Ru V. Shih, Manando Nakasaki, Harsha Kabra, and Shyni Varghese. “Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts.” Sci Adv 2, no. 8 (August 2016): e1600691. https://doi.org/10.1126/sciadv.1600691.
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  - Chiu, Yu-Jui, Wei Cai, Yu-Ru V. Shih, Ian Lian, and Yu-Hwa Lo. “A Single-Cell Assay for Time Lapse Studies of Exosome Secretion and Cell Behaviors.” Small 12, no. 27 (July 2016): 3658–66. https://doi.org/10.1002/smll.201600725.
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  - Wen, Cai, Heemin Kang, Yu-Ru V. Shih, YongSung Hwang, and Shyni Varghese. “In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells.” Drug Deliv Transl Res 6, no. 2 (April 2016): 121–31. https://doi.org/10.1007/s13346-015-0242-2.
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  - Shih, Yu-Ru, Ameya Phadke, Tomonori Yamaguchi, Heemin Kang, Nozomu Inoue, Koichi Masuda, and Shyni Varghese. “Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.” Acta Biomater 19 (June 2015): 1–9. https://doi.org/10.1016/j.actbio.2015.03.017.
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  - Kang, Heemin, Yu-Ru V. Shih, and Shyni Varghese. “Biomineralized matrices dominate soluble cues to direct osteogenic differentiation of human mesenchymal stem cells through adenosine signaling.” Biomacromolecules 16, no. 3 (March 9, 2015): 1050–61. https://doi.org/10.1021/acs.biomac.5b00099.
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  - Rao, V., Y. R. V. Shih, H. Kang, H. Kabra, and S. Varghese. “Adenosine signaling mediates osteogenic differentiation of human embryonic stem cells on mineralized matrices.” Frontiers in Bioengineering and Biotechnology 3, no. NOV (January 1, 2015). https://doi.org/10.3389/fbioe.2015.00185.
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  - Kang, Heemin, Yu-Ru V. Shih, Yongsung Hwang, Cai Wen, Vikram Rao, Timothy Seo, and Shyni Varghese. “Mineralized gelatin methacrylate-based matrices induce osteogenic differentiation of human induced pluripotent stem cells.” Acta Biomater 10, no. 12 (December 2014): 4961–70. https://doi.org/10.1016/j.actbio.2014.08.010.
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  - Kang, H., C. Wen, Y. Hwang, Y. R. V. Shih, M. Kar, S. W. Seo, and S. Varghese. “Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem cells.” Journal of Materials Chemistry B 2, no. 34 (September 14, 2014): 5676–88. https://doi.org/10.1039/c4tb00714j.
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  - Hwang, Yongsung, Samuel Suk, Yu-Ru Vernon Shih, Timothy Seo, Bin Du, Yun Xie, Ziyang Li, and Shyni Varghese. “WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment.” Sci Rep 4 (August 1, 2014): 5916. https://doi.org/10.1038/srep05916.
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  - Lee, Yuan-Wen, Ta-Liang Chen, Yu-Ru Vernon Shih, Chu-Lin Tsai, Chuen-Chau Chang, Hung-Hua Liang, Sung-Hui Tseng, Shu-Chen Chien, and Ching-Chiung Wang. “Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: A population-based study.” Cancer 120, no. 9 (May 1, 2014): 1338–44. https://doi.org/10.1002/cncr.28579.
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  - Shih, Yu-Ru V., YongSung Hwang, Ameya Phadke, Heemin Kang, Nathaniel S. Hwang, Eduardo J. Caro, Steven Nguyen, et al. “Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.” Proc Natl Acad Sci U S A 111, no. 3 (January 21, 2014): 990–95. https://doi.org/10.1073/pnas.1321717111.
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  - Kuo, Yi-Chun, Yi-Shuan Julie Li, Jing Zhou, Yu-Ru Vernon Shih, Marina Miller, David Broide, Oscar Kuang-Sheng Lee, and Shu Chien. “Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.” Plos One 8, no. 8 (2013): e71342. https://doi.org/10.1371/journal.pone.0071342.
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  - Phadke, Ameya, Yu-Ru V. Shih, and Shyni Varghese. “Mineralized synthetic matrices as an instructive microenvironment for osteogenic differentiation of human mesenchymal stem cells.” Macromol Biosci 12, no. 8 (August 2012): 1022–32. https://doi.org/10.1002/mabi.201100289.
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  - Kuo, Shu-Wen, Hsin-I Lin, Jennifer Hui-Chun Ho, Yu-Ru V. Shih, How-Foo Chen, Ta-Jen Yen, and Oscar K. Lee. “Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires.” Biomaterials 33, no. 20 (July 2012): 5013–22. https://doi.org/10.1016/j.biomaterials.2012.03.080.
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  - Lo, Ting, Chia-Feng Tsai, Yu-Ru V. Shih, Yi-Ting Wang, Sheng-Chieh Lu, Ting-Yi Sung, Wen-Lian Hsu, Yu-Ju Chen, and Oscar K. Lee. “Phosphoproteomic analysis of human mesenchymal stromal cells during osteogenic differentiation.” J Proteome Res 11, no. 2 (February 3, 2012): 586–98. https://doi.org/10.1021/pr200868p.
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  - Hung, Shun-Pei, Jennifer H. Ho, Yu-Ru V. Shih, Ting Lo, and Oscar K. Lee. “Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells.” J Orthop Res 30, no. 2 (February 2012): 260–66. https://doi.org/10.1002/jor.21517.
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  - Shih, Yu-Ru V., Kuo-Fung Tseng, Hsiu-Yu Lai, Chi-Hung Lin, and Oscar K. Lee. “Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells.” J Bone Miner Res 26, no. 4 (April 2011): 730–38. https://doi.org/10.1002/jbmr.278.
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  - Shih, Y. -. R. V., T. K. Kuo, A. -. H. Yang, O. K. Lee, and C. -. H. Lee. “Isolation and characterization of stem cells from the human parathyroid gland.” Cell Prolif 42, no. 4 (August 2009): 461–70. https://doi.org/10.1111/j.1365-2184.2009.00614.x.
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  - Kuo, Tom K., Shun-Pei Hung, Chiao-Hui Chuang, Chien-Tsun Chen, Yu-Ru V. Shih, Szu-Ching Y. Fang, Vincent W. Yang, and Oscar K. Lee. “Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells.” Gastroenterology 134, no. 7 (June 2008): 2111-2121.e3. https://doi.org/10.1053/j.gastro.2008.03.015.
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  - Chen, Chien-Tsun, Yu-Ru V. Shih, Tom K. Kuo, Oscar K. Lee, and Yau-Huei Wei. “Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells.” Stem Cells 26, no. 4 (April 2008): 960–68. https://doi.org/10.1634/stemcells.2007-0509.
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  - Ho, Jennifer Hui-Chun, Chiao-Hui Chuang, Chih-Yuan Ho, Yu-Ru Vernon Shih, Oscar Kuang-Sheng Lee, and Yeu Su. “Internalization is essential for the antiapoptotic effects of exogenous thymosin beta-4 on human corneal epithelial cells.” Invest Ophthalmol Vis Sci 48, no. 1 (January 2007): 27–33. https://doi.org/10.1167/iovs.06-0826.
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  - Shih, Yu-Ru V., Chung-Nan Chen, Shiao-Wen Tsai, Yng Jiin Wang, and Oscar K. Lee. “Growth of mesenchymal stem cells on electrospun type I collagen nanofibers.” Stem Cells 24, no. 11 (November 2006): 2391–97. https://doi.org/10.1634/stemcells.2006-0253.
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- Book Sections
  - Kang, H., Y. R. V. Shih, V. Rao, and S. Varghese. “Biomineralized matrices as intelligent scaffolds for bone tissue regeneration.” In Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2nd Edition, 59–84, 2017. https://doi.org/10.1201/9781315364698.
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  - Shih, Yuru, Ming-Te Cheng, Oscar Lee, and Yu Shih. “Tendon and ligament tissue engineering.” In Stem Cell Biology and Tissue Engineering in Dental Sciences. Academic Press, 2014.

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Education, Training, & Certifications

Subject Headings

Selected Grants

Selected Publications

Academic Articles

Book Sections