Williams Laboratory

Selected Publications

In press

Chen J, Huang D, Rubera I, Futami K, Wang PF, Zickert P, Khoo SK, Dykema KJ, Zhao P, Petillo D, Cao B, Zhang Z, Si S, Schoen SR, Yang XJ, Zhou M, Xiao GQ, Wu G, Nordenskjold M, Tauc M, Williams BO, Furge KA, Teh BT. In press. Disruption of tubular Flcn expression as a mouse model for renal tumor induction. Kidney Int. PubMed

Meng X, Vander Ark A, Lee P, Hostetter G, Bhowmick NA, Matrisian LM, Williams BO, Miranti CK, Li X. In press. Myeloid-specific TGF-β signaling in bone promotes basic-FGF and breast cancer bone metastasis. Oncogene.  PubMed

Oursler MJ, Westendorf JJ, Weivoda MM, Ruan M, Hachfeld CM, Howe A, Davey R, Zajac J, Williams BO, Khosla S. In press. Response to Wnt signaling pathways. J Bone Miner Res   PubMed

Weivoda MM, Ruan M, Hachfeld CM, Pederson L, Howe A, Davey R, Zajac J, Kobayashi Y, Williams BO, Westendorf JJ, Khosla S, Oursler MJ. In press. Wnt signaling inhibits osteoclast differentiation by activating canonical and non-canonical cAMP/PKA pathways. J Bone Miner Res.  PubMed


Zhong ZA, Zahatnansky J, Snider J, Van Wieren E, Diegel CR, Williams BO. 2015. Wntless spatially regulates bone development through β-catenin-dependent and independent mechanisms. Dev Dyn 244(10):1347–1355  PubMed

Cheng SL, Ramachandran B, Behrmann A, Shao JS, Mead M, Smith C, Krchma K, Arrendondo YB, Kovacs A, Kapoor K, Brill LM, Perera R, Williams BO, Towler DA. 2015. Vascular smooth muscle LRP6 limits arteriosclerotic calcification in diabetic LDLR–/– mice by restraining noncanonical Wnt signals. Circ Res 117(2):142–156.  PubMed

Collins CJ, Vivanco JF, Sokn SA, Williams BO, Burgers TA, Ploeg HL. 2015. Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur. J Biomech 48(2):310–317.  PubMed

Peacock JD, Dykema KJ, Toriello HV, Mooney MR, Scholten DJ 2nd, Winn ME, Borgman A, Duesbery NS, Hiemenga JA, Liu C, Campbell S, Nickoloff BP, Williams BO, Steensma MR. 2015. Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations. Am J Med Genet A 167(7):1429–1435.  PubMed

Qin L, Yin YT, Zheng FJ, Peng LX, Yang CF, Bao YN, Liang YY, Li XJ, Xiang YQ, Sun R, Li AH, Zou RH, Pei XQ, Huang BJ, Kang TB, Liao DF, Zeng YX, Williams BO, Qian CN. 2015. WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis. Oncotarget 6(12):10239–10252.   PubMed

Valkenburg KC, Hostetter G, Williams BO. 2015. Concurrent hepsin overexpression and adenomatous polyposis coli deletion causes invasive prostate carcinoma in mice. Prostate 75(14):1579–1585.    PubMed

Zhong ZA, Peck A, Li S, VanOss J, Snider J, Droscha CJ, Chang TA, Williams BO. 2015. 99mTC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice. Bone Res 3:15013.   Article


Cui Y, Niziolek PJ, MacDonald BT, Alenina N, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Powell DR, Bader M, Williams BO, Warman ML, Robling AG. 2014. Reply to Lrp5 regulation of bone mass and gut serotonin synthesis. Nat Med 20(11):1229–1230.  PubMed

Hoffmann FM, Burgers T, Mason JJ, Williams BO, Sietsema DL, Jones CB. 2014. Biomechanical evaluation of fracture fixation constructs using a variable-angle locked periprosthetic femur plate system. Injury 45(7):1035–1041   PubMed

Joiner DM, Less KD, Van Wieren EM, Hess D, Williams BO. 2014. Accelerated and increased joint damage in young mice with global inactivation of mitogen-inducible gene 6 (Mig-6) after ligament and meniscus injury. Arthritis Res Ther 16(2):R81.   PubMed

Kabiri Z, Greicius G, Madan B, Biechele S, Zhong Z, Zaribafzadeh H, Aliyed J, Wu Y, Bunte RM, Williams BO, Rossant J, Virshup DM. 2014. Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 141(11):2206–2215.      PubMed

Lim WH, Liu B, Cheng D, Williams BO, Mah SJ, Helms JA. In press. Wnt signaling regulates homeostasis of the periodontal ligament. J Periodontal Res 49(6):751–759      PubMed

Lim WH, Liu B, Cheng D, Hunter DJ, Zhong Z, Ramos DM, Williams BO, Sharpe PT, Bardet C, Mah SJ, Helms JA. 2014. Wnt signaling regulates pulp volume and dentin thickness. J Bone Miner Res 29(4):892–901. PubMed

Staal B, Williams BO, Beier F, Vande Woude GF, Zhang YW. 2014. Cartilage-specific deletion of Mig-6 results in osteoarthritis-like disorder with excessive articular chrondrocyte proliferation. Proc Natl Acad Sci U S A 111(7):2590–2595.    PubMed       Article

Williams BO. 2014. Insights into the mechanisms of sclerostin action in regulating bone mass accrual. J Bone Min Res 29(1):24–28.     PubMed


Burgers TA, Williams BO. 2013. Regulation of Wnt/β-catenin signaling within and from osteocytes. Bone 54(2):244–249. PubMed

Burgers TA, Hoffmann MF, Collins CJ, Zahatnansky J, Alvarado MA, Morris MR, Sietsma DL, Mason JJ, Jones CB, Ploeg HL, Williams BO. 2013. Mice lacking Pten in osteoblasts have improved intramembranous and late endochondral fracture healing. PLoS One 8(5):e63857. PubMed

Hu B, Chen Y, Usmani SZ, Ye S, Qiang W, Papanikolaou X, Heuck CJ, Yaccoby S, Williams BO, Van Rhee F, Barlogie B, Epstein J, Qiang YW. 2013. Characterization of the molecular mechanism of the bone-anabolic activity of carfilzomib in multiple myeloma. PLoS One 8(9):e74191. PubMed       Article

Joiner DM, Less KD, Van Wieren EM, Hess D, Williams BO. 2013. Heterozygosity for an inactivating mutation in low-density lipoprotein-related receptor 6 (Lrp6) increases osteoarthritis severity in mice after ligament and meniscus injury. Osteoarthritis Cartilage 21(10):1576–1585. PubMed                    Article

Joiner DM, Ke J, Zhong Z, Xu HE, Williams BO. 2013. LRP5 and LRP6 in development and disease. Trends Endocrin Metab 24(1):31–39.     PubMed        Article

Ke J, Xu HE, Williams BO. 2013. Lipid modification in Wnt structure and function. Curr Opin Lipidol 24(2):129–133.     PubMed

Ke J, Harikumar KG, Jurecky C, Chen C, Gu X, Wang L, Parker N, Cheng Z, Xu W, Williams BO, Melcher K, Miller LJ, Xu HE. 2013. Structure and function of Norrin in assembly and activation of a Frizzled 4–Lrp5/6 complex. Genes Dev 27(21):2305–2319. PubMed

Loftus JC, Dhruv H, Tuncali S, Kloss J, Yang Z, Schumacher CA, Cao B, Williams BO, Eschbacher JM, Ross JTD, Tran NL. 2013. TROY (TNFRSF19) promotes glioblastoma cell survival signaling and therapeutic resistance. Mol Cancer Res 11(8): 865–874. PubMed

Maupin KA, Droscha CJ, Williams BO. 2013. A comprehensive overview of skeletal phenotypes associated with alterations in Wnt/β-catenin signaling in humans and mice. Bone Res 1(1):27–71. Article

Riddle RC, Diegel CR, Leslie KM, Van Koevering KK, Faugere MC, Clemens TL, Williams BO. 2013. Lrp5 and Lrp6 exert overlapping functions in osteoblasts during postnatal bone acquisition. PLoS One 8(5):e63323. PubMed       Article

Steensma MR, Tyler WK, Shaber AG, Goldring SR, Ross FP, Williams BO, Healey JH, Purdue PE. 2013. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One 8(7):e69101. PubMed       Article

Valkenburg KC, Steensma MR, Williams BO, Zhong Z. 2013. Skeletal metastasis: treatments, mouse models, and the Wnt signaling. Chin J Cancer 32(7):380–396. PubMed


Fortin SP, Ennis MJ, Schumacher CA, Zylstra-Diegel CR, Williams BO, Ross JTD, Winkles JA, Loftus JC, Symons MH, Tran NL. 2012. Cdc42 and the guanine nucleotide exchange factors Ect2 and Trio mediate Fn14-Rac1-induced migration and invasion of glioblastoma cells. Mol Cancer Res 10(7):958–968. PubMed        Article

Ke J, Zhang C, Harikumar KG, Zylstra-Diegel CR, Wang L, Mowry LE, Miller LJ, Williams BO, Xu HE. 2012. Modulation of β-catenin signaling by glucagon receptor activation. PLoS One 7(3):e33676. PubMed

Li Y, Ferris A, Lewis BC, Orsulic S, Williams BO, Holland EC, Hughes SH. 2012. The RCAS/TVA somatic gene transfer method in modeling human cancer. In Genetically Engineered Mice for Cancer Research, J.E. Green and T. Ried, eds. Berlin: Springer Verlag, pp. 83–112. Chapter

Regard JB, Zhong Z, Williams BO, Yingzi Y. 2012. Wnt signaling in bone development and disease: making stronger bones with Wnts. Cold Spring Harb Perspect Biol4(12):a007997. PubMed

Zhong Z, Williams BO. 2012. Integration of cellular adhesion and Wnt signaling: interactions between N-cadherin and LRP5 and their role in regulating bone mass. J Bone Miner Res27(9):1849–1851. PubMed

Zhong Z, Williams BO, Steensma MR. 2012. The activation of β-catenin by Gαs contributes to the etiology of phenotypes seen in fibrous dysplasia and McCune-Albright syndrome. IBMS BoneKEy 9:113. Article

Zhong Z, Baker JJ, Zylstra-Diegel CR, Williams BO. 2012. Lrp5 and Lrp6 play compensatory roles in mouse intestinal development. J Cell Biochem 113(1):31–38. PubMed

Zhong Z, Zylstra-Diegel CR, Schumacher CA, Baker JJ, Carpenter AC, Rao S, Yao W, Guan M, Helms JA, Lane NE, Lang RA, Williams BO. 2012. Wntless functions in mature osteoblasts to regulate bone mass. Proc Natl Acad Sci U S A 109(33): E2197–E2204.   PubMed     Article


Cui Y, Niziolek PJ, MacDonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong Z, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang QM, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG. 2011. Lrp5 functions in bone to regulate bone mass. Nat Med17(6):684–691. PubMed     Article

Joeng KS, Schumacher C, Zylstra-Diegel CR, Long F, Williams BO. 2011. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol 359(2):222–229. PubMed

Qian CN, Williams BO. 2011. The induction of high endothelial venule remodeling by primary tumors does not correlate to the metastatic capability of tumor cells. J Blood Lymph 1(1):e102. Article

Stefater JA 3rd, Lewkowich I, Rao S, Mariggi G, Carpenter AC, Burr AR, Fan J, Ajima R, Molkentin JD, Williams BO, Wills-Karp M, Pollard JW, Yamaguchi T, Ferrara N, Gerhardt H, Lang RA. 2011. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature 474(7352):511–515. PubMed      Article

Valkenburg KC, Williams BO. 2011. Mouse models of prostate cancer. Prostate Cancer 2011: 22 pp. Article

Wan M, Li J, Herbst K, Zhang J, Yu B, Wu X, Qiu T, Lei W, Lindvall C, Williams BO, Ma H, Zhang F, Cao X. 2011. LRP6 mediates cAMP generation by G protein–coupled receptors through regulating the membrane targeting of Gαs. Sci Signal 4(164):ra15. PubMed


Coulibaly MO, Sietsema DL, Burgers TA, Mason J, Williams BO, Jones CB. 2010. Recent advances in the use of serological bone formation markers to monitor callus development and fracture healing. Crit Rev Eukaryot Gene Expr 20(2):105–127. PubMed

Diegel CR, Cho KR, El-Naggar AK, Williams BO, Lindvall C. 2010. Mammalian target of rapamycin-dependent acinar cell neoplasia after inactivation of Apc and Pten in the mouse salivary gland: implications for human acinic cell carcinoma. Cancer Res 70(22):9143–9152. PubMed      Article

Mason JJ, Williams BO. 2010. SOST and DKK: antagonists of LRP family signaling as targets for treating bone disease. J Osteoporos 2010:9 pp. PubMed


Badders NM, Goel S, Clark RJ, Klos KS, Kim S, Bafico A, Lindvall C, Williams BO, Alexander CM. 2009. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS One 4(8):e6594.     PubMed

Castilho RM, Squarize CH, Chodosh LA, Williams BO, Gutkind JS. 2009. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell 5(3):279–289.       PubMed

Lindvall C, Zylstra CR, Evans N, West RA, Dykema K, Furge KA, Williams BO. 2009. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS One 4(6):e5813.        PubMed

Qian CN, Furge KA, Knol J, Huang D, Chen J, Dykema KJ, Kort EJ, Massie A, Khoo SK, Vanden Beldt K, Resau JH, Anema J, Kahnoski RJ, Morreau H, Camparo P, Comperat E, Sibony M, Denoux Y, Molinie V, Vieillefond A, Eng C, Williams BO, Teh BT. 2009. Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: identification in human tumors and confirmation in animal models. Cancer Res 69(21):8256–8264.      PubMed

Williams BO, Insogna KL. 2009. Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J Bone Miner Res 24(2):171–178. PubMed


Chen J, Futami K, Petillo D, Peng J, Wang P, Knol J, Li Y, Khoo SK, Huang D, Qian CN, Zhao P, Dykema K, Zhang R, Cao B, Yang XJ, Furge K, Williams BO, Teh BT. 2008. Deficiency of FLCN in mouse kidney led to development of polycystic kidneys and renal neoplasia. PLoS One 3(10):e3581. PubMed 

Qian Z, Chen L, Fernald AA, Williams BO, Le Beau MM. 2008. A critical role for Apc in hematopoietic stem and progenitor cell survival. J Exp Med 205(9):2163–2175. PubMed       Article  

Robinson DR, Zylstra CR, Williams BO. 2008. Wnt signaling and prostate cancer. Curr Drug Targets 9(7):571–580. PubMed

Shekhar MPV, Gerard B, Pauley RJ, Williams BO, Tait L. 2008. Rad6B is a positive regulator of β-catenin stabilization. Cancer Res 68(6):1741–1750.    PubMed    Article  

VanKoevering KK, Williams BO. 2008. Transgenic mouse strains for conditional gene deletion during skeletal development. IBMS BoneKEy 5(5):151–170.

Wang P, Bowl MR, Bender S, Peng J, Farber L, Chen J, Ali A, Zhang Z, Alberts AS, Thakker RV, Shilatifard A, Williams BO, Teh BT. 2008. Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice. Mol Cell Biol 28(9):2930–2940.    PubMed        Article  

Wolf J, Palmby TR, Gavard J, Williams BO. 2008. Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6. FEBS Letters 582(2): 255–261. PubMed  Article  


Bruxvoort KJ, Charbonneau HM, Giambernardi TA, Goolsby JC, Qian CN, Zylstra CR, Robinson DR, Roy-Burman P, Shaw AK, Buckner-Berghuis BD, Sigler RE, Resau JH, Sullivan R, Bushman W, Williams BO. 2007. Inactivation of Apc in the mouse prostate causes prostate carcinoma. Cancer Res 67(6):2490–2496. PubMed        Article  

Hinoi T, Akyol A, Theisen BK, Ferguson DO, Greenson JK, Williams BO, Cho KR, Fearon ER. 2007. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res 67(20):9721–9730. PubMed        Article  

Lindvall C, Bu W, Williams BO, Li Y. 2007. Wnt signaling, stem cells, and the cellular origin of breast cancer. Stem Cell Rev 3(2):157–168.      PubMed  

Liu X, Bruxvoort KJ, Zylstra CR, Liu J, Cichowski R, Faugere MC, Bouxsein ML, Wan C, Williams BO, Clemens TL. 2007. Lifelong accumulation of bone in mice lacking Pten in osteoblasts. Proc Natl Acad Sci 104(7):2259–2264.   PubMed      Article  

Wu R, Hendrix-Lucas N, Kuick R, Zhai Y, Schwartz DR, Akyol A, Hanash S, Misek DE, Katabuchi H, Williams BO, Fearon ER, Cho KR. 2007. Mouse model of human ovarian endometroid adenocarcinoma based on somatic defects in the Wnt β-catenin and PI3K/Pten signaling pathways. Cancer Cell 11(4):321–333.  PubMed      Article  

Young JJ, Bromberg-White JL, Zylstra CR, Church JT, Boguslawski E, Resau JH, Williams BO, Duesbery NS. 2007. LRP5 and LRP6 are not required for protective antigen–mediated internalization or lethality of anthrax lethal toxin. PLoS Pathog 3(3):e27.     PubMed      Article  


Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL. 2006. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126(5):955–968.    PubMed    

Lindvall C, Evans NC, Zylstra CR, Li Y, Alexander CM, Williams BO. 2006. The Wnt signaling receptor LRP5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis. J Biol Chem 281(46):35081–35087.      PubMed                 

Park KS, Jeon SH, Kim SE, Bahk YY, Holmen SL, Williams BO, Chung KC, Surh YJ, Choi KY. 2006. APC inhibits ERK pathway activation and cellular proliferation induced by Ras. J Cell Sci119(5):819–827.    PubMed       Article  

Wang PF, Kong D, VanBrocklin MW, Peng J, Zhang C, Potter SJ, Gao X, Teh BT, Zhang N, Williams BO, Holmen SL. 2006. Simplified method for the construction of gene targeting vectors for conditional gene inactivation in mice. Transgenics 4:215–228.

Zhang C, Kong D, Tan MH, Pappas DL Jr, Wang PF, Chen J, Farber L, Zhang N, Koo HM, Weinreich M, Williams BO, Teh BT. 2006. Parafibromin inhibits cancer cell growth and causes G1 phase arrest. Biochem Biophys Res Commun 350(1):17–24.  PubMed    Article  


Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. 2005. Prostaglandin E2 promotes colon cancer cell growth through a GS-axin-β-catenin signaling axis. Science 310(5753):1504–1510. PubMed    Article  

Holmen SL, Williams BO. 2005. Essential role for Ras signaling in glioblastoma maintenance. Cancer Res 65(18) 8250–8255.   PubMed    Article  

Holmen SL, Zylstra CR, Mukherjee A, Sigler R, Faugere MC, Bouxsein M, Deng L, Clemens T, Williams BO. 2005. Essential role of ß-catenin in postnatal bone acquisition. J Biol Chem 280(22):21162–21168.  PubMed     Article  

Holmen SL, Robertson SA, Zylstra CR, Williams BO. 2005. Wnt-independent activation of ß-catenin mediated by a Dkk-1-Frizzled 5 fusion protein. Biochem Biophys Res Commun 328(2): 533–539.        PubMed    Article  

Qian CN, Knol J, Igarashi P, Lin F, Zylstra U, Teh BT, Williams BO. 2005. Cystic renal neoplasia following conditional inactivation of Apc in mouse renal tubular epithelium. J Biol Chem280(5): 3938–3945.   PubMed    Article