Yang
Laboratory

Skeletal Biology

The skeletal system develops from mesenchymal cells and is the major reservoir of mesenchymal stem cells (MSCs) in adult life. MSCs play pivotal roles in skeletal tissue growth, homeostasis and repair, while dysregulations in MSC renewal, linage specification, and pool maintenance are common causes of skeletal disorders. Our long-term interest is to investigate the signals and cellular processes orchestrating the activities of MSCs and MSC-derived cells during skeletal development and homeostasis, and how they are involved in skeletal aging and disorders.

Projects

1. Sumoylation pathway in skeletal development and diseases
2. LRP1 signaling in skeletal development and diseases

As part of these projects, we have established in vivo and in vitro genetic models to study the molecular mechanisms underlying osteoarthritis and osteoporosis.

Our Impact

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  • 121 peer-reviewed papers published in 2023
  • 62 peer-reviewed papers published in high-impact journals in 2023
  • 55 clinical trials launched to date

Tao Yang, Ph.D.

Associate Professor, Department of Cell Biology

Areas of Expertise

Skeletal development and aging, osteoarthritis, osteoporosis, skeletal stem cells, sumoylation, signaling pathways

Biography

Dr. Yang received his B.S. in biochemistry from Wuhan University, and his Ph.D. in biochemistry from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (SIBCB, CAS). He then joined Baylor College of Medicine as a postdoctoral fellow working with Drs. Paul Overbeek and Brendan Lee. In 2009, he began serving as an instructor in the Department of Molecular and Human Genetics at Baylor. Dr. Yang joined VAI as an assistant professor in February 2013.

SELECTED PUBLICATIONS

Floramo JS, Molchanov V, Liu H, Liu Y, Craig SEL, Yang T. 2023. An integrated view of stressors as causative agents in OA pathogenesis. Biomolecules 13(5):721.

Liu H, Zhai L, Liu Y, Lu D, Vander Ark A, Yang T*, Krawczyk CM*. 2023. The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclastsSci Adv 9(14).
*Co-corresponding authors

Liu H, Liu Y, Jin SG, Johnson J, Xuan H, Lu D, Li J, Zhai L, Li X, Zhao Y, Liu M, Craig SEL, Floramo JS, Molchanov V, Li J, Li JD, Krawczyk C, Shi X, Pfeifer GP, Yang T. 2023.  TRIM28 secures skeletal stem cell fate during skeletogenesis by silencing neural gene expression and repressing GREM1/AKT/mTOR signaling axis. Cell Rep 42(1):112012.

Liu H, Craig SEL, Molchanov V, Floramo JS, Zhao Y, Yang T. 2022. SUMOylation in skeletal development, homeostasis, and disease. Cells 11(17):2710.

Mark PR, Murray SA, Yang T, Eby A, Lai A, Lu D, Zieba J, Rajasekaran S, VanSickle EA, Rossetti LZ, Guidugli L, Watkins K, Wright MS, Bupp CP, Prokop JW. 2022. Autosomal recessive LRP1-related syndrome featuring cardiopulmonary dysfunction, bone dysmorphology, and corneal clouding. Cold Spring Harb Mol Case Stud 8(6):a006169.

Yang CH*, Fagnocchi L*, Apostle S, Wegert V, Casani-Galdón S, Landgraf K, Panzeri I, Dror E, Heyne S, Wörpel T, Chandler DP, Lu D, Yang T, Gibbons E, Guerreiro R, Brás J, Thomasen M, Grunnert LG, Vaag AA, Gillberg L, Grundberg, E, Conesa A, Körner A, PERMUTE, Pospisilik JA. 2022. Independent phenotypic plasticity axes define distinct obesity subtypesNat Metab.
*Co-first authorship
**Highlighted in News & Views

Liu Y, Molchanov V, Yang T. 2021. Enzymatic machinery of ubiquitin and ubiquitin-like modification systems in chondrocyte homeostasis and osteoarthritisCurr Rheumatol Rep 23:62.

Foxa GE, Liu Y, Turner LM, Robling AG, Yang T, Williams BO. 2021. Generation and characterization of mouse models for skeletal disease. Methods Mol Biol 2221:165–191.

Wang W, Wang M, Ruan Y, Tan J, Wang H, Yang T, Li J, Zhou Q. 2019. Ginkgolic acids impair mitochondrial function by decreasing mitochondrial biogenesis and promoting FUNDC1-dependent mitophagyJ Agric Food Chem 67(36):10097–10106.

He Y, Shi J, Nguyen QT, You E, Liu H, Ren X, Wu Z, Li J, Qiu W, Khoo SK, Yang T, Yi W, Sun F, Xi Z, Huang X, Melcher K, Min B, Xu HE. 2019. Development of highly potent glucocorticoids for steroid-resistant severe asthmaProc Natl Acad Sci U S A 116(14):6932–6937.

Lu D, Li J, Liu H, Foxa GE, Weaver K, Li J, Williams BO, Yang T. 2018. LRP1 suppresses bone resorption in mice by inhibiting the RANKL-stimulated NFκB and p38 pathways during osteoclastogenesisJ Bone Miner Res.

Maupin K, Weaver K, Bergsma A, Christie C, Zhong Z, Yang T, Williams BO. 2018. Enhanced cortical bone expansion in Lgals3-deficient mice during agingBone Res 6(7).

Liu H, Li J Lu D, Li J, Liu M, Williams BO, Li J, Yang T. 2018. Ginkgolic acid, a sumoylation inhibitor, promotes adipocyte commitment but suppresses adipocyte terminal differentiation of mouse bone marrow stromal cellsSci Rep 8:2545.

Li J, Lu D, Dou H, Liu H, Weaver K, Wang W, Li J, Yeh ETH, Williams BO, Zheng L, Yang T. 2018. Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathwayNat Commun. 9:143.

Yang T, Williams BO. 2017. Low-density lipoprotein receptor-related proteins in skeletal development and diseasePhysiol Rev 97(3):1211-1228.

Li J, Lu D, Liu H, Williams BO, Overbeek P, Lee B, Zheng L, Yang T. 2017. Deficiency of SCLT1 causes cystic kidney by activating ERK and STAT3 signalingHum Mol Genet 26(15):2949–2960.

Grafe I, Alexander S, Yang T, Lietman C, Homan EP, Munivez E, Chen Y, Jiang MM, Bertin T, Dawson B, Asuncion F, Ke HZ, Ominsky MS, Lee B. 2016. Sclerostin antibody treatment improves the bone phenotype of Crtap-/- mice, a model of recessive Osteogenesis ImperfectaJ Bone Miner Res 31(5):1030–1040.

He Y, Shi J, Yi W, Ren X, Gao X, Li J, Wu N, Weaver K, Xie Q, Khoo SK, Yang T, Huang X, Melcher K, Xu HE. 2016. Discovery of a highly potent glucocorticoid for asthma treatment. Cell Disc doi:10.1038/celldisc.2015.35.

Lu L, Harutyunyan K, Jin W, Wu J, Yang T, Chen Y, Joeng KS, Bae Y, Tao J, Dawson BC, Jiang MM, Lee B, Wang LL. 2015. RECQL4 regulates p53 function in vivo during skeletogenesisJ Bone Miner Res 30(6):1077–1089

Chen S, Grover M, Sibai T, Black J, Rianon N, Rajagopal A, Munivez E, Bertin T, Dawson B, Chen Y, Jiang MM, Lee B, Yang T, Bae Y. 2015. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeletonMol Genet Metab 115(1):53–60.

Grafe I, Yang T, Alexander S, Homan EP, Lietman C, Jiang MM, Bertin T, Munivez E, Chen Y, Dawson B, Ishikawa Y, Weis MA, Sampath TK, Ambrose C, Eyre D, Bächinger HP, Lee B. 2014. Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta.  Nat Med 20(6):670–675.

Yang T, Grafe I, Bae Y, Chen S, Chen Y, Bertin TK, Jiang M-M, Ambrose CG, Lee B.  2013. E-selectin ligand 1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment.  Proc Natl Acad Sci USA 110(18):7336–7341.

Chen S, Tao J, Bae Y, Jiang MM, Bertin TK, Chen Y, Yang T, Lee B. 2012. Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9J Bone Miner Res 28(3):649–659.

Bae Y, Yang T*, Zheng HC*, Campeau P, Chen Y, Bertin T, Dawson B, Munivez E, Tao J, Lee B. 2012. miRNA-34c regulates Notch signaling during bone developent.  Hum Mol Genet 21(13):2991–3000.
*Contributed equally

Keller B, Yang T, Chen Y, Munivez E, Bertin TK, Zabel B, Lee B. 2011. Interaction of TGF- β and BMP signaling pathways during chondrogenesisPLoS One 6(1):e16421.

Yang T, Mendoza RL, Lu H, Li K, Tao J, Shah R, Keller B, Jiang M-M, Chen Y, Bertin TK, Dabovic B, Engin F, Rifkin DB, Hicks J, Jamrich M, Beaudet AL, Lee B. 2010. E-Selectin Ligand 1 regulates growth plate homeostasis by inhibiting the intracellular processing and secretion of mature transforming growth factor βJ Clin Invest 120(7):2474–2485.

Tao J, Chen S, Yang T, Dawson B, Munivez E, Bertin T, Lee B.  2010. Osteosclerosis due to Notch gain of function is solely Rbpj-dependentJ Bone Miner Res 25(10):2175–2183.

Mao J, Yang T, Gu Z, Heird WC, Finegold MJ, Lee B, Wakil SJ. 2009. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues under lipogenic conditions.  Proc Natl Acad Sci USA 106(41):17576–17581.

Jiang M, Gao Y, Yang T, Zhu X, Chen J.  2009. Cyclin Y, a novel membrane-associated cyclin, interacts with PFTK1FEBS Lett 583(13):2171–2178.

Engin F, Yao Z*, Yang T*, Zhou G, Bertin TK, Jiang MM, Chen Y, Wang L, Zheng H, Sutton RE, Boyce BF, Lee B. 2008. Dimorphic effects of Notch signaling in bone homeostasisNat Med 14(3):299–205.
*Contributed equally

Gao Y, Jiang M, Yang T, Ni J, Chen J. 2006. A Cdc2-related protein kinase hPFTAIRE1 from human brain interacting with 14-3-3 proteinsCell Res 16(6):539–547.

Chen Q, Liang D, Yang T, Leone G, Overbeek PA. 2004. Distinct roles of individual E2Fs in induction of cell cycle entry in postmitotic lens fiber cells of transgenic miceDev Neurosci 26(506):435–445.

Yang T*, Liang D, Koch PJ, Hohl D, Kheradmand F, Overbeek PA*. 2004. Epidermal detachment, desmosomal dissociation and destabilization of corneodesmosin in Spink5-/- miceGenes Dev 18(19):2354–2358.
*Corresponding authors

Yang T, Gao Y-K, Chen J-Y.  2002. KIAA0202, a human septin family member, interacting with hPFTAIRE1Acta Biochem Biophys Sin 34(4):520–525.

Yang T, Chen J-Y.  2001. Identification and cellular localization of human PFTAIRE1Gene 267(2):165–172.

Book chapters

Yang T, Gover M, Joeng K, Lee B. 2017. Fetal and neonatal bone development. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. American Society for Bone and Mineral Research.

Yang T, Gover M, Joeng K, Lee B. 2013. Fetal and neonatal bone development.  Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 8th ed. Wiley-Blackwell.

Gavin Cai

Student Intern, Yang Laboratory

Mentor: Tao Yang, Ph.D.

Joe Floramo, M.S.

Ph.D. Candidate, VAI Graduate School

Thesis: Polysumoylation’s role in skeletal development and homeostasis

Mentor: Tao Yang, Ph.D.

Wendy Fritz

Senior Administrative Assistant I, Department of Cell Biology

Mu-Nung Hsu, Ph.D.

Research Scientist, Yang Laboratory

Caleb Inman

Student Intern, Yang Laboratory

Mentor: Tao Yang, Ph.D.

Ye Liu, Ph.D.

Research Scientist, Yang Laboratory

Desumoylation pathways in joint aging and osteoarthritis pathogenesis

Mentor: Tao Yang, Ph.D.

Di Lu, M.S.

Research Associate, Department of Cell Biology

Vladimir Molchanov

Ph.D. Candidate, VAI Graduate School

Thesis: Engineering stem cells to treat osteoarthritis

Mentor: Tao Yang, Ph.D.

Yaguang Zhao, Ph.D.

Postdoctoral Fellow, Yang Laboratory

Mentor: Tao Yang, Ph.D.

Lab Alumni

Liam Beck

Intern

Denise Bilboa

Intern

Jayme Gross

Intern

Jianshaung Li, Ph.D.

Postdoctoral Fellow

Huadie Liu, Ph.D.

Postdoctoral Fellow

Rashika Shrestha

Intern

Leah Thompson

Intern

Ethan Vanhoose

Intern

Yuk Kei Wan

Intern