Research
Focus areas
Get a PDF of all our related research publications.
Dr. Westendorf's Skeletal Development and Regeneration Research Lab has three main research focus areas. Dr. Westendorf receives grant funding from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) within the U.S. National Institutes of Health (NIH). The lab collaborates with many other Mayo Clinic investigators.
Cartilage biology and osteoarthritis
We're studying protein phosphatase PHLPP1 and other proteins that regulate cartilage development and osteoarthritis progression.
Related publications
Arnold KM, Weaver SR, Zars EL, Tschumperlin DJ, Westendorf JJ. Inhibition of Phlpp1 preserves the mechanical integrity of articular cartilage in a murine model of post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2024 Mar 1:S1063-4584(24)00933-6. doi: 10.1016/j.joca.2024.01.008. PMID: 38432607.
Arnold KM, Sicard D, Tschumperlin DJ, Westendorf JJ. Atomic Force Microscopy Micro-Indentation Methods for Determining the Elastic Modulus of Murine Articular Cartilage. Sensors (Basel). 2023 Feb 7;23(4):1835. doi: 10.3390/s23041835. PMID: 36850434 Free PMC article.
Taylor EL, Weaver SR, Lorang IM, Arnold KM, Bradley EW, Marron Fernandez de Velasco E, Wickman K, Westendorf JJ. GIRK3 deletion facilitates kappa opioid signaling in chondrocytes, delays vascularization and promotes bone lengthening in mice. Bone. 2022 Jun;159:116391. doi:10.1016/j.bone.2022.116391. Epub 2022 Mar 18. PMID: 35314385 Free PMC article.
Taylor EL, Weaver SR, Zars EL, Turner CA, Buhrow SA, Reid JM, Bradley EW, Westendorf JJ. Chondrocytic and pharmacokinetic properties of Phlpp inhibitors. Osteoarthr Cartil Open. 2021 Jun 8;3(3):100190. doi: 10.1016/j.ocarto.2021.100190. eCollection 2021 Sep.PMID: 36474816 Free PMC article.
Weaver SR, Taylor EL, Zars EL, Arnold KM, Bradley EW, Westendorf JJ. Pleckstrin homology (PH) domain and leucine rich repeat phosphatase 1 (Phlpp1) suppresses parathyroid hormone receptor 1 (Pth1r) expression and signaling during bone growth. J Bone Miner Res. 2021 Oct;36(10):2100-2101. doi: 10.1002/jbmr.4340. Epub 2021 Jun 4. PMID: 34086369
Castillejo Becerra CM, Mattson AM, Molstad DHH, Lorang IM, Westendorf JJ, Bradley EW. DNA methylation and FoxO3a regulate PHLPP1 expression in chondrocytes. Journal of Cellular Biochemistry. 2018; doi:10.1002/jcb.27056.
Hwang SM, Feigenson M, Begun DL, Carpio Shull LR, Culley KL, Otero M, Goldring MB, Ta LE, Kakar S, Bradley EW, JJ Westendorf JJ. Phlpp inhibitors block pain and cartilage degradation associated with osteoarthritis. 1 Journal of Orthopaedic Research. 2018; doi:10.1002/jor.23781.
Bradley EW, Carpio LR, McGee-Lawrence ME, Castillejo Becerra C, Amanatullah DF, Ta LE, Otero M, Goldring MB, Kakar S, Westendorf JJ. Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis. Osteoarthritis and Cartilage. 2016; doi:10.1016/j.joca.2015.12.014.
Bradley EW, Carpio LR, Newton AC, Westendorf JJ. Deletion of the PH-domain and leucine-rich repeat protein phosphatase 1 (Phlpp1) increases fibroblast growth factor (Fgf) 18 expression and promotes chondrocyte proliferation. Journal of Biological Chemistry. 2015; doi:10.1074/jbc.M114.612937.
Bradley EW, Carpio LR, Westendorf JJ. Histone deacetylase 3 suppression increases PH domain and leucine-rich repeat phosphatase (Phlpp)1 expression in chondrocytes to suppress Akt signaling and matrix secretion. Journal of Biological Chemistry. 2013; doi:10.1074/jbc.M112.423723.
Bone biology and bone diseases
We're studying histone deacetylases (HDACs) and other proteins, including Girk3, that regulate bone mass and strength.
Related publications
Torres HM, Hinojosa L, VanCleave AM, Rodezno T, Westendorf JJ, Tao J. Hdac1 and Hdac2 positively regulate Notch1 gain-of-function pathogenic signaling in committed osteoblasts of male mice. Birth Defects Res. 2024 Jan;116(1):e2266. doi: 10.1002/bdr2.2266. Epub 2023 Nov 3. PMID: 37921375.
Torres HM, Yeo D, Westendorf JJ. Pulling rank with RNA: RANKL promotes the association of PGC-1β/RNA complexes with NCoR/HDAC3 to activate gene expression in osteoclasts. Mol Cell. 2023 Oct 5;83(19):3397-3399. doi: 10.1016/j.molcel.2023.09.012. PMID: 37802020.
McGee-Lawrence ME, Pierce JL, Yu K, Culpepper NR, Bradley EW, Westendorf JJ. Loss of Hdac3 in osteoprogenitors increases bone expression of osteoprotegerin, improving systemic insulin sensitivity. Journal of Cellular Physiology. 2018; doi:10.1002/jcp.26148.
Feigenson M, Shull LC, Taylor EL, Camilleri ET, Riester SM, van Wijnen AJ, Bradley EW, Westendorf JJ. Histone deacetylase 3 deletion in mesenchymal progenitor cells hinders long bone development. Journal of Bone and Mineral Research. 2017; doi:10.1002/jbmr.3236.
McGee-Lawrence ME, Carpio LR, Schulze RJ, Pierce JL, McNiven MA, Farr JN, Khosla S, Oursler MJ, Westendorf JJ. Hdac3 deficiency increases marrow adiposity and induces lipid storage and glucocorticoid metabolism in osteochondroprogenitor cells. Journal of Bone and Mineral Research. 2016; doi:10.1002/jbmr.2602.
Carpio LR, Bradley EW, McGee-Lawrence ME, Weivoda MM, Poston DD, Dudakovic A, Xu M, Tchkonia T, Kirkland JL, van Wijnen AJ, Oursler MJ, Westendorf JJ. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling. Science Signaling. 2016; doi:10.1126/scisignal.aaf3273.
Dudakovic A, Evans JM, Li Y, Middha S, McGee-Lawrence ME, van Wijnen AJ, Westendorf JJ. Histone deacetylase inhibition promotes osteoblast maturation by altering the histone H4 epigenome and reduces Akt phosphorylation. Journal of Biological Chemistry. 2013; doi:10.1074/jbc.M113.489732.
McGee-Lawrence ME, Bradley EW, Dudakovic A, Carlson SW, Ryan ZC, Kumar R, Dadsetan M, Yaszemski MJ, Chen Q, An KN, Westendorf JJ. Histone deacetylase 3 is required for maintenance of bone mass during aging. Bone. 2013; doi:10.1016/j.bone.2012.10.015.
McGee-Lawrence ME, McCleary-Wheeler AL, Secreto FJ, Razidlo DF, Zhang M, Stensgard BA, Li X, Stein GS, Lian JB, Westendorf JJ. Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts. Bone. 2011; doi:10.1016/j.bone.2011.01.007.
Razidlo DF, Whitney TJ, Casper ME, McGee-Lawrence ME, Stensgard BA, Secreto FJ, Li X, Knutson SK, Hiebert SW, Westendorf JJ. Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat. PLOS One. 2010; doi:10.1371/journal.pone.0011492.
Schroeder TM, Kahler RA, Li X, Westendorf JJ. Histone deacetylase 3 interacts with Runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. Journal of Biological Chemistry. 2004; doi:10.1074/jbc.M403702200.
Bone cancers and cancer-associated bone disease
We're studying chromosomal translocations and bone cancers, including primary and metastatic tumors.
Related publications
Dong Z, Yeo KS, Lopez G, Zhang C, Dankert Eggum EN, Rokita JL, Ung CY, Levee TM, Her ZP, Howe CJ, Hou X, van Ree JH, Li S, He S, Tao T, Fritchie K, Torres-Mora J, Lehman JS, Meves A, Razidlo GL, Rathi KS, Weroha SJ, Look AT, van Deursen JM, Li H, Westendorf JJ, Maris JM, Zhu S. GAS7 Deficiency Promotes Metastasis in MYCN-Driven Neuroblastoma. Cancer Res. 2021 Jun 1;81(11):2995-3007. doi: 10.1158/0008-5472.CAN-20-1890. Epub 2021 Feb 18. PMID: 33602789 Free PMC article.
Taylor EL, Westendorf JJ. Histone Mutations and Bone Cancers. Adv Exp Med Biol. 2021;1283:53-62. doi: 10.1007/978-981-15-8104-5_4. PMID: 33155137.
Blackburn PR, Carter JM, Oglesbee D, Westendorf JJ, Neff BA, Stichel D, Tsen DW, Gavrilova RH, Wesseling P, von Deimling A, Caulfield TR, Klee EW, Pusch S, Inwards CY. An activating germline IDH1 variant associated with a tumor entity characterized by unilateral and bilateral chondrosarcoma of the mastoid. HGG Adv. 2020 Aug 24;1(1):100006. doi: 10.1016/j.xhgg.2020.100006. eCollection 2020 Oct 22. PMID: 35047830 Free PMC article.
Berent TE, Dorschner JM, Craig TA, Drake MT, Westendorf JJ, Kumar R. Lung tumor cells inhibit bone mineralization and osteoblast activity. Biochemical and Biophysical Research Communications. 2019; doi:10.1016/j.bbrc.2019.09.045.
Yang Y, Bai Y, He Y, Zhao Y, Chen J, Ma L, Pan Y, Hinten M, Zhang J, Karnes RJ, Kohli M, Westendorf JJ, Li B, Zhu R, Huang H, Xu W. PTEN loss promotes intratumoral androgen synthesis and tumor microenvironment remodeling via aberrant activation of RUNX2 in castration-resistant prostate cancer. Clinical Cancer Research. 2018; doi:10.1158/1078-0432.CCR-17-2006.
Fang D, Gan H, Lee JH, Han J, Wang Z, Riester SM, Jin L, Chen J, Zhou H, Wang J, Zhang H, Yang N, Bradley EW, Ho TH, Rubin BP, Bridge JA, Thibodeau SN, Ordog T, Chen Y, van Wijnen AJ, Oliveira AM, Xu RM, Westendorf JJ, Zhang Z. The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science. 2016; doi:10.1126/science.aae0065.
Wang X, Bledsoe KL, Graham RP, Asmann YW, Viswanatha DS, Lewis JE, Lewis JT, Chou MM, Yaszemski MJ, Jen J, Westendorf JJ, Oliveira AM. Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. Nature Genetics. 2014; doi:10.1038/ng.2989.
Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW. The t(8; 21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Molecular and Cellular Biology. 1998; doi:10.1128/mcb.18.1.322.
Funding
Dr. Westendorf's lab has received research funding from a variety of organizations through the years. Current grants include:
| Investigator & Role |
Grant Title |
Funding Source |
Duration |
| Jennifer J. Westendorf, Ph.D., principal investigator |
Musculoskeletal Research Training Program (T32 AR56950) |
NIH/NIAMS |
2024-2029 |
| Jennifer Westendorf, Ph.D., principal investigator |
Girk3 in Bone Biology and Disease (K99 AR080745) |
NIH/NIAMS |
2023-2028 |
| Jennifer J. Westendorf, Ph.D., principal investigator |
PHLPP Phosphatases in Osteoarthritis (R01 AR078552) |
NIH/NIAMS |
2022-2027 |
| Jennifer J. Westendorf, Ph.D., program director/principal investigator |
PHLPP Inhibition and Osteoarthritis-Associated Pain (R21 AR082134) |
NIH/NIAMS |
2022-2024 |
Research collaborators
Research collaborations help advance scientific discovery. Our lab collaborates with other investigators at Mayo Clinic on our main research projects. Contact us if you're interested in possible collaborative opportunities.
Our current Mayo Clinic research collaborators are: