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Smoothened stimulation by membrane sterols drives Hedgehog pathway activity.

Deshpande I, Liang J, Hedeen D, Roberts KJ, Zhang Y, Ha B, Latorraca NR, Faust B, Dror RO, Beachy PA, Myers BR, Manglik A.

Nature. 2019 Jul;571(7764):284-288. doi: 10.1038/s41586-019-1355-4. Epub 2019 Jul 1.


Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched.

Zhang Y, Bulkley DP, Xin Y, Roberts KJ, Asarnow DE, Sharma A, Myers BR, Cho W, Cheng Y, Beachy PA.

Cell. 2018 Nov 15;175(5):1352-1364.e14. doi: 10.1016/j.cell.2018.10.026. Epub 2018 Nov 8.


Cilia-Associated Oxysterols Activate Smoothened.

Raleigh DR, Sever N, Choksi PK, Sigg MA, Hines KM, Thompson BM, Elnatan D, Jaishankar P, Bisignano P, Garcia-Gonzalo FR, Krup AL, Eberl M, Byrne EFX, Siebold C, Wong SY, Renslo AR, Grabe M, McDonald JG, Xu L, Beachy PA, Reiter JF.

Mol Cell. 2018 Oct 18;72(2):316-327.e5. doi: 10.1016/j.molcel.2018.08.034.


Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration.

Lu WJ, Mann RK, Nguyen A, Bi T, Silverstein M, Tang JY, Chen X, Beachy PA.

Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):E200-E209. doi: 10.1073/pnas.1719109115. Epub 2017 Dec 26.


Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium.

Myers BR, Neahring L, Zhang Y, Roberts KJ, Beachy PA.

Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11141-E11150. doi: 10.1073/pnas.1717891115. Epub 2017 Dec 11.


Hedgehog mediated degradation of Ihog adhesion proteins modulates cell segregation in Drosophila wing imaginal discs.

Hsia EYC, Zhang Y, Tran HS, Lim A, Chou YH, Lan G, Beachy PA, Zheng X.

Nat Commun. 2017 Nov 2;8(1):1275. doi: 10.1038/s41467-017-01364-z.


The Stromal Niche for Epithelial Stem Cells: A Template for Regeneration and a Brake on Malignancy.

Roberts KJ, Kershner AM, Beachy PA.

Cancer Cell. 2017 Oct 9;32(4):404-410. doi: 10.1016/j.ccell.2017.08.007. Review.


Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells.

Zhao C, Cai S, Shin K, Lim A, Kalisky T, Lu WJ, Clarke MF, Beachy PA.

Science. 2017 Apr 21;356(6335). pii: eaal3485. doi: 10.1126/science.aal3485. Epub 2017 Mar 9.


Pharmacological rescue of diabetic skeletal stem cell niches.

Tevlin R, Seo EY, Marecic O, McArdle A, Tong X, Zimdahl B, Malkovskiy A, Sinha R, Gulati G, Li X, Wearda T, Morganti R, Lopez M, Ransom RC, Duldulao CR, Rodrigues M, Nguyen A, Januszyk M, Maan Z, Paik K, Yapa KS, Rajadas J, Wan DC, Gurtner GC, Snyder M, Beachy PA, Yang F, Goodman SB, Weissman IL, Chan CK, Longaker MT.

Sci Transl Med. 2017 Jan 11;9(372). pii: eaag2809. doi: 10.1126/scitranslmed.aag2809.


Control of inflammation by stromal Hedgehog pathway activation restrains colitis.

Lee JJ, Rothenberg ME, Seeley ES, Zimdahl B, Kawano S, Lu WJ, Shin K, Sakata-Kato T, Chen JK, Diehn M, Clarke MF, Beachy PA.

Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7545-E7553. Epub 2016 Nov 4.


Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance.

Jeong Y, Hoang NT, Lovejoy A, Stehr H, Newman AM, Gentles AJ, Kong W, Truong D, Martin S, Chaudhuri A, Heiser D, Zhou L, Say C, Carter JN, Hiniker SM, Loo BW Jr, West RB, Beachy P, Alizadeh AA, Diehn M.

Cancer Discov. 2017 Jan;7(1):86-101. doi: 10.1158/2159-8290.CD-16-0127. Epub 2016 Sep 23.


Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

Loh KM, Chen A, Koh PW, Deng TZ, Sinha R, Tsai JM, Barkal AA, Shen KY, Jain R, Morganti RM, Shyh-Chang N, Fernhoff NB, George BM, Wernig G, Salomon REA, Chen Z, Vogel H, Epstein JA, Kundaje A, Talbot WS, Beachy PA, Ang LT, Weissman IL.

Cell. 2016 Jul 14;166(2):451-467. doi: 10.1016/j.cell.2016.06.011.


Endogenous B-ring oxysterols inhibit the Hedgehog component Smoothened in a manner distinct from cyclopamine or side-chain oxysterols.

Sever N, Mann RK, Xu L, Snell WJ, Hernandez-Lara CI, Porter NA, Beachy PA.

Proc Natl Acad Sci U S A. 2016 May 24;113(21). doi: 10.1073/pnas.1604984113. Epub 2016 May 9.


Localized JNK signaling regulates organ size during development.

Willsey HR, Zheng X, Carlos Pastor-Pareja J, Willsey AJ, Beachy PA, Xu T.

Elife. 2016 Mar 14;5. pii: e11491. doi: 10.7554/eLife.11491.


Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma.

Ally MS, Ransohoff K, Sarin K, Atwood SX, Rezaee M, Bailey-Healy I, Kim J, Beachy PA, Chang AL, Oro A, Tang JY, Colevas AD.

JAMA Dermatol. 2016 Apr;152(4):452-6. doi: 10.1001/jamadermatol.2015.5473.


A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response.

Oh S, Kato M, Zhang C, Guo Y, Beachy PA.

PLoS One. 2015 Aug 13;10(8):e0135804. doi: 10.1371/journal.pone.0135804. eCollection 2015.


The role of ciliary trafficking in Hedgehog receptor signaling.

Kim J, Hsia EY, Brigui A, Plessis A, Beachy PA, Zheng X.

Sci Signal. 2015 Jun 2;8(379):ra55. doi: 10.1126/scisignal.aaa5622.


Bifurcating action of Smoothened in Hedgehog signaling is mediated by Dlg5.

Chong YC, Mann RK, Zhao C, Kato M, Beachy PA.

Genes Dev. 2015 Feb 1;29(3):262-76. doi: 10.1101/gad.252676.114.


Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein.

Strating JR, van der Linden L, Albulescu L, Bigay J, Arita M, Delang L, Leyssen P, van der Schaar HM, Lanke KH, Thibaut HJ, Ulferts R, Drin G, Schlinck N, Wubbolts RW, Sever N, Head SA, Liu JO, Beachy PA, De Matteis MA, Shair MD, Olkkonen VM, Neyts J, van Kuppeveld FJ.

Cell Rep. 2015 Feb 3;10(4):600-15. doi: 10.1016/j.celrep.2014.12.054. Epub 2015 Jan 29.


Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate.

Lim A, Shin K, Zhao C, Kawano S, Beachy PA.

Nat Cell Biol. 2014 Dec;16(12):1135-45. doi: 10.1038/ncb3057. Epub 2014 Nov 2.


Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.

Shin K, Lim A, Zhao C, Sahoo D, Pan Y, Spiekerkoetter E, Liao JC, Beachy PA.

Cancer Cell. 2014 Oct 13;26(4):521-33. doi: 10.1016/j.ccell.2014.09.001.


Simultaneous measurement of smoothened entry into and exit from the primary cilium.

Kim J, Hsia EY, Kim J, Sever N, Beachy PA, Zheng X.

PLoS One. 2014 Aug 13;9(8):e104070. doi: 10.1371/journal.pone.0104070. eCollection 2014.


Stromal response to Hedgehog signaling restrains pancreatic cancer progression.

Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, Fitamant J, Jones PD, Ghanta KS, Kawano S, Nagle JM, Deshpande V, Boucher Y, Kato T, Chen JK, Willmann JK, Bardeesy N, Beachy PA.

Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3091-100. doi: 10.1073/pnas.1411679111. Epub 2014 Jul 14.


Identification of recurrent SMO and BRAF mutations in ameloblastomas.

Sweeney RT, McClary AC, Myers BR, Biscocho J, Neahring L, Kwei KA, Qu K, Gong X, Ng T, Jones CD, Varma S, Odegaard JI, Sugiyama T, Koyota S, Rubin BP, Troxell ML, Pelham RJ, Zehnder JL, Beachy PA, Pollack JR, West RB.

Nat Genet. 2014 Jul;46(7):722-5. doi: 10.1038/ng.2986. Epub 2014 May 25. Erratum in: Nat Genet. 2015 Jan;47(1):97.


Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma.

Shin K, Lim A, Odegaard JI, Honeycutt JD, Kawano S, Hsieh MH, Beachy PA.

Nat Cell Biol. 2014 May;16(5):469-78. doi: 10.1038/ncb2956. Epub 2014 Apr 20. Erratum in: Nat Cell Biol. 2014 Jun;16(6):620.


Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma.

Kim DJ, Kim J, Spaunhurst K, Montoya J, Khodosh R, Chandra K, Fu T, Gilliam A, Molgo M, Beachy PA, Tang JY.

J Clin Oncol. 2014 Mar 10;32(8):745-51. doi: 10.1200/JCO.2013.49.9525. Epub 2014 Feb 3.


Hedgehog pathway modulation by multiple lipid binding sites on the smoothened effector of signal response.

Myers BR, Sever N, Chong YC, Kim J, Belani JD, Rychnovsky S, Bazan JF, Beachy PA.

Dev Cell. 2013 Aug 26;26(4):346-57. doi: 10.1016/j.devcel.2013.07.015. Epub 2013 Aug 15.


FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension.

Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El-Bizri N, Sawada H, Haghighat R, Chan R, Haghighat L, de Jesus Perez V, Wang L, Reddy S, Zhao M, Bernstein D, Solow-Cordero DE, Beachy PA, Wandless TJ, Ten Dijke P, Rabinovitch M.

J Clin Invest. 2013 Aug;123(8):3600-13. doi: 10.1172/JCI65592. Epub 2013 Jul 15.


Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists.

Kim J, Aftab BT, Tang JY, Kim D, Lee AH, Rezaee M, Kim J, Chen B, King EM, Borodovsky A, Riggins GJ, Epstein EH Jr, Beachy PA, Rudin CM.

Cancer Cell. 2013 Jan 14;23(1):23-34. doi: 10.1016/j.ccr.2012.11.017. Epub 2013 Jan 3.


Scube/You activity mediates release of dually lipid-modified Hedgehog signal in soluble form.

Creanga A, Glenn TD, Mann RK, Saunders AM, Talbot WS, Beachy PA.

Genes Dev. 2012 Jun 15;26(12):1312-25. doi: 10.1101/gad.191866.112. Epub 2012 Jun 7.


Identification of a cKit(+) colonic crypt base secretory cell that supports Lgr5(+) stem cells in mice.

Rothenberg ME, Nusse Y, Kalisky T, Lee JJ, Dalerba P, Scheeren F, Lobo N, Kulkarni S, Sim S, Qian D, Beachy PA, Pasricha PJ, Quake SR, Clarke MF.

Gastroenterology. 2012 May;142(5):1195-1205.e6. doi: 10.1053/j.gastro.2012.02.006. Epub 2012 Feb 11.


Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling.

Kim MS, Saunders AM, Hamaoka BY, Beachy PA, Leahy DJ.

Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13112-7. doi: 10.1073/pnas.1109877108. Epub 2011 Jul 26.


Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder.

Shin K, Lee J, Guo N, Kim J, Lim A, Qu L, Mysorekar IU, Beachy PA.

Nature. 2011 Apr 7;472(7341):110-4. doi: 10.1038/nature09851. Epub 2011 Mar 9.


Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma.

Monje M, Mitra SS, Freret ME, Raveh TB, Kim J, Masek M, Attema JL, Li G, Haddix T, Edwards MS, Fisher PG, Weissman IL, Rowitch DH, Vogel H, Wong AJ, Beachy PA.

Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4453-8. doi: 10.1073/pnas.1101657108. Epub 2011 Mar 1.


Hedgehogs, flies, Wnts and MYCs: the time has come for many things in medulloblastoma.

Monje M, Beachy PA, Fisher PG.

J Clin Oncol. 2011 Apr 10;29(11):1395-8. doi: 10.1200/JCO.2010.34.0547. Epub 2011 Feb 28. No abstract available.


Patterning axon targeting of olfactory receptor neurons by coupled hedgehog signaling at two distinct steps.

Chou YH, Zheng X, Beachy PA, Luo L.

Cell. 2010 Sep 17;142(6):954-66. doi: 10.1016/j.cell.2010.08.015.


Interactions between Hedgehog proteins and their binding partners come into view.

Beachy PA, Hymowitz SG, Lazarus RA, Leahy DJ, Siebold C.

Genes Dev. 2010 Sep 15;24(18):2001-12. doi: 10.1101/gad.1951710. Review.


Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector.

Kim J, Lee JJ, Kim J, Gardner D, Beachy PA.

Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13432-7. doi: 10.1073/pnas.1006822107. Epub 2010 Jul 12.


Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth.

Kim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, Chong CR, Chang KS, Fereshteh M, Gardner D, Reya T, Liu JO, Epstein EH, Stevens DA, Beachy PA.

Cancer Cell. 2010 Apr 13;17(4):388-99. doi: 10.1016/j.ccr.2010.02.027.


Dally-like core protein and its mammalian homologues mediate stimulatory and inhibitory effects on Hedgehog signal response.

Williams EH, Pappano WN, Saunders AM, Kim MS, Leahy DJ, Beachy PA.

Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5869-74. doi: 10.1073/pnas.1001777107. Epub 2010 Mar 15.


Genetic and biochemical definition of the Hedgehog receptor.

Zheng X, Mann RK, Sever N, Beachy PA.

Genes Dev. 2010 Jan 1;24(1):57-71. doi: 10.1101/gad.1870310.


Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus.

Kim J, Kato M, Beachy PA.

Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21666-71. doi: 10.1073/pnas.0912180106. Epub 2009 Dec 8.


Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans.

Roessler E, Ma Y, Ouspenskaia MV, Lacbawan F, Bendavid C, Dubourg C, Beachy PA, Muenke M.

Hum Genet. 2009 May;125(4):393-400. doi: 10.1007/s00439-009-0628-7. Epub 2009 Jan 31.


Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia.

Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, Kwon HY, Kim J, Chute JP, Rizzieri D, Munchhof M, VanArsdale T, Beachy PA, Reya T.

Nature. 2009 Apr 9;458(7239):776-9. doi: 10.1038/nature07737. Erratum in: Nature. 2009 Jul 30;460(7255):652.


The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla.

McLellan JS, Zheng X, Hauk G, Ghirlando R, Beachy PA, Leahy DJ.

Nature. 2008 Oct 16;455(7215):979-83. doi: 10.1038/nature07358. Epub 2008 Sep 14.


Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer.

Kumar SK, Roy I, Anchoori RK, Fazli S, Maitra A, Beachy PA, Khan SR.

Bioorg Med Chem. 2008 Mar 15;16(6):2764-8. doi: 10.1016/j.bmc.2008.01.012. Epub 2008 Jan 11.


Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response.

Gerdes JM, Liu Y, Zaghloul NA, Leitch CC, Lawson SS, Kato M, Beachy PA, Beales PL, DeMartino GN, Fisher S, Badano JL, Katsanis N.

Nat Genet. 2007 Nov;39(11):1350-60. Epub 2007 Sep 30.


Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.

Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN, Matsui W.

Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4048-53. Epub 2007 Feb 27.


Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice.

Akiyama H, Stadler HS, Martin JF, Ishii TM, Beachy PA, Nakamura T, de Crombrugghe B.

Matrix Biol. 2007 May;26(4):224-33. Epub 2006 Dec 8.


Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells.

Dwyer JR, Sever N, Carlson M, Nelson SF, Beachy PA, Parhami F.

J Biol Chem. 2007 Mar 23;282(12):8959-68. Epub 2007 Jan 2.

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