Shim Lab


2022





  • Kim JM, Yang YS, Xie J, Lee O, Kim JH, Hong J, Boldyreff B, Filhol-Cochet O, Chun H, Greenblatt MB, Gao G, and Shim JH. Regulation of sclerostin by the SIRT1 stabilization pathway in osteocytes. Cell Death Differ. Feb 15, 2022

  • Greenblatt MB*, Shim JH*, Bok S, and Kim JM. The ERK MAPK pathway in osteoblasts. J. Bone Metabol. 29(1):1-15, 2022 (*co-corresponding authorship)​

  • Eekhoff EMW., de Ruiter RD., Smilde BJ, de Vries T., Schoenmaker T., Netelenbos CN., Hsiao E., Pals G., Shim JH, Gao G., Kaplan F. Pignolo R., and Micha M. Gene therapy in Fibrodysplasia Ossificans Progressiva (FOP): Feasibility and obstacles. Human Gene Ther. 33(15-16):782-788, 2022

  • John AA, Xie J, Yang YS, Kim JM, Lin C, Ma H, Gao G, and Shim JH. AAV-mediated delivery of osteoblast/osteoclast-regulating miRNAs for osteoporosis therapy. Mol Ther Nuc Acids. 29:296-311, 2022

  • Kim JM, Yang YS, Hong JH, Chaugule S, Chun H, van der Meulen M, Greenblatt MB, and Shim JH. Biphasic regulation of osteoblast development via the ERK MAPK-mTOR pathway. eLife, 11:e78069, 2022

  • Yang YS, Kim JM, Xie J, Chaugule S, Lin C, Ma H, Hsiao E, Hong JH, Chun H, Shore EM, Kaplan FS, Gao G, and Shim JH. Suppression of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva Using AAV Gene Therapy. Nat. Commun. 13(1):6175.

  • Oh WT, Yang YS, Xie J, Ma H, Kim JM, Park KH, Oh DS, Park-Min KH, Greenblatt MB, Gao G, and Shim JH. WNT-modulating gene silencers as a gene therapy for osteoporosis, bone fracture, and critical-sized bone defects. Mol. Ther. S1525-0016(22), 2022.

  • Lin C, Yang Q, Gao D, Xie J, Yang YS, Chaugule S, DeSouZa N, Oh WT, Li R, Chen Z, John AA, Qui A, Zhu LJ, Greenblatt MB, Ghosh S, Li S, Gao G, Haynes C, Emerson CP, and Shim JH. Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration. Nat. Commun. 13(1):6869.



2021





  • Park Y, Cheong E, Kwak JG, Carpenter R, Shim JH, Lee J. Trabecular skeletal organoid model substantiates the regulation of localized bone surface remodeling. Sci. Adv. 7(4):eabd6495, 2021

  • Sun J, Shin DY, Eiseman M, Yallowitz AR, Li N, Lalani S, Li Z, Cung M, Bok S, Debnath S, Marquez SJ, White TE, Khan AG, Lorenz IC, Shim JH, Lee FS, Xu R, Greenblatt MB. SLITRK5 is a novel negative regulator of hedgehog signaling in osteoblasts. Nat. Commun. 12(1):4611, 2021

  • Yoon DS, Lee KM, Cho S, Ko EA, Kim J, Jung S, Shim JH, Gao G, Park KH, Lee JW. Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage. Int. J. Mol. Sci. 18(5):3353-3360, 2021

  • Chaugule S, Kim JM, Yang YS, Knobeloch KP, He X, Shim JH. Deubiquitinating Enzyme USP8 is Essential for Skeletogenesis by Regulating Wnt Signaling. Int. J. Mol. Sci. 22(19):10289, 2021



2020





  • Kim JM, Yang YS, Park KH, Ge X, Xu R, Li N, Song M, Chun H, Bok S, Charles JF, Filhol-Cochet O, Boldyreff B, Dinter T, Yu PB, Kon N, Gu W, Takarada T, Greenblatt MB, Shim JH. A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation. Nat Commun. 2020 05 08; 11(1):2289. PMID: 32385263.

  • Li Z, Oh H, Cung M, Marquez SJ, Sun J, Hammad H, Janssens S, Pouliot P, Lambrecht BN, Yang YS, Shim JH*, Greenblatt MB. TAOK3 is a MAP3K contributing to osteoblast differentiation and skeletal mineralization. Biochem Biophys Res Commun. 2020 10 22; 531(4):497-502. PMID: 32807497 *(Co-corresponding authorship)

  • Kim JM, Lin C, Stavre Z, Greenblatt MB, Shim JH. Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells. 2020 Sep 10; 9(9). PMID: 32927921.

  • Bok S, Shin DY, Yallowitz AR, Eiseman M, Cung M, Xu R, Li N, Sun J, Williams AL, Scott JE, Su B, Shim JH, Greenblatt MB. MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. Nat Commun. 2020 11 11; 11(1):5704. PMID: 33177525.



2019





  • Yang YS, Xie J, Wang D, Kim JM, Tai PWL, Gravallese E, Gao G, Shim JH. Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis. Nat Commun. 2019 Jul 04; 10(1):2958. PMID: 31273195.
  • Kim MJ, Min Y, Shim JH, Chun E, Lee KY. CRBN Is a Negative Regulator of Bactericidal Activity and Autophagy Activation Through Inhibiting the Ubiquitination of ECSIT and BECN1. Front Immunol. 2019; 10:2203. PMID: 31620128.
  • Yang YS, Xie J, Chaugule S, Wang D, Kim JM, Kim J, Tai PWL, Seo SK, Gravallese E, Gao G, Shim JH. Bone-Targeting AAV-Mediated Gene Silencing in Osteoclasts for Osteoporosis Therapy. Mol Ther Methods Clin Dev. 2020 Jun 12; 17:922-935. PMID: 32405514.
  • Kim MJ, Yang YS, Park KH, Oh HH, Greenblatt MB, Shim JH. The ERK MAPK Pathway is Essential for skeletal Development and Homeostasis. Int J Mol Sci; 2019 Apr; 20(8):1803. PMID: 31013682.


2018





  • Young Kim, Zhe Zhang, Jae-Hyuck Shim, Tae Sup Lee, and Ching-Hsuan Tung. A cell surface clicked navigation system to direct specific bone targeting. Bioorganic med. Chem. 26(3):758. 2018
  • Ren Xu, Alisha Yallowitz, An Qin, Zhuhao Wu, Dong Yeon Shin, Jung-Min Kim, Shawn Debnath, Gang Ji, Mathias P. Bostrom, Xu Yang, Han Dong, Pouneh Kermani, Sarfaraz Lalani, Na Li, Yifang Liu, Michael G. Poulos, Amanda Wach, Yi Zhang, Kazuki Inoue, Annarita Di Lorenzo, Baohong Zhao, Jason M. Butler, Jae-Hyuck Shim, Lauire H. Glimcher, Matthew B. Greenblatt. Targeting skeletal endothelium to ameliorate bone loss. Nat. Med., 24(6):823-833, 2018
  • Shawn Debnath,Alisha Yallowitz, Jason McComick, Sarfaraz Lalani, Tuo Zhang, Ren Xu, Yifang Liu, Yeon-Suk Yang, Jae-Hyuck Shim, Meera Hameed, John H. Healey, Dan Avi Landau, Matthew B. Greenblatt. Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing. Nature, 562 (7725):133-139, 2018


2017





  • Stanley Adoro, Kwang Hwan Park, Sarah E Bettigole, Raphael Lis, Hee Rae Shin, Heewon Seo, Ju Han Kim, Klaus-Peter Knobeloch, Jae-Hyuck Shim*, and Laurie H. Glimcher. Post-translational control of T cell development by the ESCRT protein CHMP5. Nat. Immunol. 18(7), 780-790, 2017 *(Co-corresponding authorship)
  • Ren Xu, Chao Zhang, Dong Yeon Shin, Jung-Min Kim, Sarfaraz Lalani, Na Li, Yeon-Suk Yang, Yifang Liu, Mark Eiseman, Roger J. Davis, Jae-Hyuck Shim* and Matthew B. Greenblatt. c-Jun N-terminal kinases (JNKs) are critical mediators of osteoblast activity in vivo. J. Bone. Miner. Res. 32(9), 1811-1815, 2017 *(Co-corresponding authorship)
  • Jae-Hyuck Shim, Zheni Stavre, Ellen Gravallese. Bone loss in Rheumatoid arthritis: Basic mechanisms and Clinical implications. Calcif. Tissue Int. Dec. 4th, 2017


2016





  • Matthew B. Greenblatt, Dong Yeon Shin, Hwanhee Oh, Ki-young Lee, Bo Zhai, Steven P. Gygi, Sutada Lotinun, Roland Baron, Dou Liu, Bing Su, Laurie H. Glimcher, and Jae-Hyuck Shim. MEKK2 mediates an alternative pathway for activation of β-catenin that promotes bone formation. Proc. Natl. Acad. Sci, USA. 113 (9):E1226-35, 2016.


2015





  • Gyuyoung Moon, Juhong Kim, Yoon Min, Sae Mi Wi, Jae-Hyuck Shim, Eunyoung Chun, and Ki-Young Lee. Phosphoinositide-dependent kinase-1 inhibits TRAF6 ubiquitination by interrupting the formation of TAK1-TAB2 complex in TLR4 signaling. Cell Signal, 27(12): 2524-33.
  • Daniel S Oh, Alia Koch, Sidney Eisig, Sahng Gyoon Kim, Yoon Hyuck Kim, Do-Gyoon Kim, and Jae-Hyuck Shim. Distinctive capillary action by micro-channels in bone-like templates can enhance recruitment of cells for restoration of large bony defect. J Vis Exp, Sep 11 (103). 2015
  • Matthew B. Greenblatt, Kwang Hwan Park, Hwanhee Oh, Jung-Min Kim, Dong Yeon Shin, Jae Myun Lee, Jin Woo Lee, Anju Singh, Ki-young Lee, Dorothy Hu, Changchun Xiao, Julia F. Charles, Josef M. Penninger, Sutada Lotinun, Roland Baron, Sankar Ghosh, and Jae-Hyuck Shim. CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts. J. Exp. Med.,212(8):1283-301, 2015
  • Matthew B. Greenblatt, Jung-Min Kim, Hwanhee Oh, Kwang Hwan Park, Min-Kyung Choo, Yasuyo Sano, Coralee E. Tye, Ziedonis Skobe, Roger J. Davis, Jin Mo Park, Marianna Bei, Laurie H. Glimcher, and Jae-Hyuck Shim. p38-alpha MAPK is required for tooth morphogenesis and enamel secretion. J. Biol. Chem., 290 (1):284-95, 2015.
  • Sae Mi Wi, Jeongho Park, Jae-Hyuck Shim, Eunyoung Chun, and Ki-Young Lee. Ubiquitination of ECSIT is crucial for the activation of p65/p50 NF-κBs in Toll-like receptor 4 signaling. Mol. Biol. Cell, 26 (1):151-160, 2015.
  • Paraskevi-Rea Oikonomidou, Casu Carla, Zhiwei Yang, Bart Crielaard, Jae-Hyuck Shim, Stefano Rivella, Maria G Vogiatzi. Polycythemia is associated with bone loss and reduced osteoblast activity in mice. Osteoporos Int. Dec, 2015


2014





  • So Yong Kim, Kyung-Hwa Baik, Kwan-Hyuck Baek, Kyong-Hwa Chah, Kyung Ah Kim, Gyuyoung Moon, Eunyu Jung, Seong-Tae Kim, Jae-Hyuck Shim, Matthew B. Greenblatt, Eunyoung Chun and Ki-Young Lee. S6K1 Negatively Regulates TAK1 Activity in the Toll-Like Receptor Signaling Pathway. Mol. Cell Biol., 34 (3):510-521, 2014.
  • Sae Mi Wi, Gyuyoung Moon, Juhong Kim, Seong-Tae Kim, Jae-Hyuck Shim, Eunyoung Chun, and Ki-Young Lee. TAK1-ECSIT-TRAF6 Complex Plays a Key Role in the TLR4 Signal to Activate NF-κB. J. Biol. Chem.,289:35205-35214, 2014.


2013





  • So Yong Kim, Sookyung Jeong, Kyong-Hwa Chah, Eunyu Jung, Kwan-Hyuck Baek, Seong-Tae Kim, Jae-Hyuck Shim, Eunyoung Chun, and Ki-Young Lee. Salt-inducible kinase 1 and 3 negatively regulate toll-like receptor 4 -mediated signal. Mol Endocrinol, September, 2013.
  • Kwang Hwan Park, Boryung Park, Dong Suk Yoon, Seung-Hyun Kwon, Dong Min Shin, Jin Woo Lee2, Hyun Gyu Lee, Jae-Hyuck Shim, Jeon Han Park, and Jae Myun Lee. Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway. Cell Communication and Signaling, In press, 2013.
  • Matthew B Greenblatt and Jae-Hyuck Shim. OsteoImmunology: A Brief Introduction. Immune Netw., 13(4):111-115, 2013.
  • Jae-Hyuck Shim*, Matthew B. Greenblatt, Weigou zou, Zhiwei Huang, Marc Wein, Nicholas Brady, Dorothy Hu, Jean Charron, heather Brodkin, Gregory Petsko, Dennis Zaller, Bo Zhai, Steven Gygi, Laurie H. Glimcher, Dallas Jones. Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J. Clin. Invest., 123(9):4010-22, 2013. *(Co-corresponding authorship)
  • Matthew B. Greenblatt, Jae-Hyuck Shim*, Laurie H. Glimcher, Mitogen Activated Kinase Pathways in Osteoblasts. Ann. Rev. Cell Dev. Biol. In press, 2013. *(Co-first authorship).
  • Tae-Yoon Park, Seung-Hyung Kim, Yoon-Chul Shin, Nae-Hyun Lee, Christina Rae-Kyung Lee, Jae-Hyuck Shim, Laurie H. Glimcher, Inhee Mook-Jung, Eunji Cheong, Won-Ki Kim, and Jong-Soon Lim, and Sang-Kyou Lee. Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin. J. Control Release. 163:307-315, 2013.


2012





  • Marc N. Wein, Dallas C. Jones, Jae-Hyuck Shim, Antonios O. Aliprantis, Rosalyn Sulyanto, Vanja Lazarevic, Sandra L. Poliachik, Ted S. Gross, and Laurie H. Glimcher. Control of bone resorption in mice by Schnurri-3. Proc. Natl. Acad. Sci, USA. 109:8173-8178, 2012.

  • So Young Kim, Jae-Hyuck Shim, Eunyoung Chun, Ki-Young Lee. Reciprocal inhibition between transforming growth factor-b-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated kinase kinase kinases, and its suppression by the TAK1-binding protein 2 (TAB2), an adaptor protein for TAK1. J. Biol. Chem., 285:3381-3391, 2012.
  • Jae-Hyuck Shim*, Matthew B. Greenblatt, Anju Singh, Nicholas Brady, Dorothy Hu, Rebecca Drapp, Wataru Ogawa, Masato Kasuga, Tetsuo Noda, Sang-kyou Lee, Sang-hwa Yang, Vivienne I. Rebel, and Laurie H. Glimcher. Administration of recombinant BMP2/7 in utero reverses Rubinstein Taybi Syndrome-like skeletal defects induced by Pdk1 or Cbp mutations. J. Clin. Invest., 122:91-106, 2012 *(Co-corresponding authorship).


2011





  • Weiguo Zou, Matthew B. Greenblatt, Jae-Hyuck Shim, Shashi Kant, Bo Zhai, Sutada Lotinun, Nicholas Brady, Dorothy Hu, Steven P. Gygi, Roland Baron, Roger J. Davis, Dallas Jones, and Laurie H Glimcher. MLK3 regulates bone development downstream of the Faciogenital Dysplasia protein FGD1. J. Clin. Invest., 121:4383-4392, 2011.
  • Vanja Lazarevic, Xi Chen, Jae-Hyuck Shim, Eun-Sook Hwang, Alexandra N. Bolm, Mohamed Oukka, Ann-Hwee Lee, Vijay K. Kuchroo and Laurie H. Glimcher. T-bet represses TH17 differentiation through transcriptional blockade of the TH17 regulator RORgt. Nat. Immunol., 12:96-104, 2011.
  • Weiguo Zou, Xie Chen, Jae-Hyuck Shim, Zhiwei Huang, Nicholas Brady, Dorothy Hu, Rebecca Drapp, Kirsten Sigrist, Laurie H. Glimcher, and Dallas Jones. The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid. Nat. Cell Biol., 13:59-65, 2011.


2010





  • Min-Jung Shin, Jae-Hyuck Shim, Jae-Young Lee, Wook-Jin Chae, Heung-Kyu Lee, Tomohiro Morio, Jun Han Park, Eun-Ju Chang, and Sang-Kyou Lee. Qualitative and quantitative differences in the intensity of Fas-mediated intracellular signals determine life and death in T cells. Int. J. Hematol., 92: 262-270, 2010.
  • Matthew B. Greenblatt, Jae-Hyuck Shim*, Weiguo Zou, Despina Sitara, Michelle Schweitzer, Dorothy Hu, Sutada Lotinun, Yasuyo Sano, Roland Baron, Jin Mo Park, Simon Arthur, Min Xie, Michael D. Schneider, Bo Zhai, Steven Gygi, Roger Davis, and Laurie H Glimcher. A MAPK pathway essential for bone homeostasis. J. Clin. Invest., 120:2457-73, 2010. *(Co-first authorship)
  • Matthew B. Greenblatt, Jae-Hyuck Shim, and Laurie H. Glimcher. TAK1 mediates BMP signaling in cartilage. Ann. N.Y. Acad. Sci., 1192: 385-390, 2010.


2009 ~





  • Jae-Hyuck Shim, Matthew B. Greenblatt, Min Xie, Michael D. Schneider, and Laurie H. Glimcher. TAK1 is an essential regulator of BMP signaling in cartilage. EMBO J., 28:2028-2041, 2009.
  • So Yong Kim, Hee-Yeon Jo, Mi Hye Kim, Yun-yi Cha, Sung Won Choi, Jae-Hyuck Shim, Tae Jin Kim and Ki-Young Lee. H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of IPLA2 activity. J. Biol. Chem., 283: 33563-33568, 2008.
  • Heidi Mendoza, David G. Campbell, Kerry Burness, James Hastie, Natalia Ronkina, Jae-hyuck Shim, J. Simon C. Arthur, Roger J. Davis, Matthias Gaestel, Gary L. Johnson, Sankar Ghosh and Philip Cohen. Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex.Biochem. J., 409:711-722, 2008.
  • Jae-Hyuck Shim, Changchun Xiao, Matthew S. Hayden, Ki-young Lee, E. Sergio Trombetta, Marc Pypaert, Atsuki Nara, Tamotsu Yoshimori, Bettina Wilm, Richard A. Flavell, Hediye Grdjument-Bromage, Paul Tempst, Brigid LM Hogan, Ira Mellman and Sankar Ghosh. CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis. J. Cell Biol., 172:1045-56, 2006.
  • Michael J. May, Signe E. Larsen, Jae-Hyuck Shim, Lisa A. Madge and Sankar Ghosh. A novel ubiquitin-like domain in IkB-kinase b is required for functional activity of the kinase. J. Biol. Chem., 279:45528-39, 2004
  • Changchun Xiao, Jae-Hyuck ShimZhang, Chen Dong, Richard A. Flavell, Xin-Yuan Fu, Jeffrey L. Wrana, Brigid L.M. Hogan and Sankar Ghosh Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. Genes Dev., 17:2933-49, 2003.

  • Jae-Hyuck Shim, Heung-Kyu Lee, Eun-Ju Chang, Wook-Jin Chae, Jin-Hwan Han, Duck-Jong Han, Tomohiro Morio, Jung-Jin Yang, Alfred Bothwell and Sang-Kyou Lee. Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. Proc. Natl. Acad. Sci, USA. 99:10617-22, 2002.

  • Jae-Hyuck Shim, Hyung-Jung Kim, Jung-Hee Lim, Sang-Kyou Lee. Functions of Ich-1L and Ich-1S in Apoptotic Signaling of Jurkat T cells. Kor. J. Immunol., 20:91-99, 1998.

  • Jae-young, Lee, Jae-Hyuck Shim, Jung-Hee Lim, Yong-Sub Song, Sang-Kyou Lee. Supplement of Incomplete Apoptosis Through CD8/Fas Chimeric Molecule By PMA or IFN-g. Kor. J. Immunol., 20:203-209, 1998.


Jae-Hyuck Shim, Ph.D.

Associate Professor of Medicine/Rheumatology and Horae gene Therapy Center
Director of Bone Analysis Core
Umass Chan Medical School

Jaehyuck.Shim@umassmed.edu

FOP Gene Therapy at Umass-2021