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Selected Publications

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Full publication list available here.

Wang, Q., Asarnow, D.E., Ding, K., Mann, R.K., Hatakeyama, J., Zhang, Y., Ma, Y., Cheng, Y., Beachy, P.A. Dispatched uses Na+ flux to power release of lipid-modified Hedgehog. Nature 599(7884): 320-324 (2021). Pubmed

Zhang, Y., Lu, W.J., Bulkley, D.P., Liang, J., Ralko, A., Han, S., Roberts, K.J., Li, A., Cho, W., Cheng, Y., Manglik, A., Beachy, P.A. Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit. Proc Natl Acad Sci U S A.117(46):28838-28846 (2020). Pubmed

Deshpande, I., Liang J., Hedeen, D., Roberts, K.J., Zhang, Y., Ha, B., Latorraca, N.R., Faust, B., Dror R.O., Beachy, P.A., Myers, B.R., Manglik, A. Smoothened stimulation by membrane sterols drives Hedgehog pathway activity. Nature 571(7764): 284-288 (2019). Pubmed

Zhang, Y., Bulkley, D., Xin, Y., Roberts, K., Asarnow, D., Sharma, A., Myers, B., Cho, W., Cheng, Y., Beachy, P.A. Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched. Cell, 175(5):1352-1364 (2018). Pubmed

Raleigh, D.R., Sever, N., Choksi, P.K., Sigg, M.A., Hines, K.M., Thompson, B.M., Elnatan, D., Jaishankar, P., Bisignano, P., Garcia-Gonzalo, F.R., Krup, A.L., Eberl, M., Byrne, E.F.X., Siebold, C., Wong, S.Y., Renslo, A.R., Grabe, M., McDonald, J.G., Xu, L., Beachy, P.A., Reiter, J.F. Cilia-Associated Oxysterols Activate Smoothened. Mol Cell, 72(2):316-327 (2018). Pubmed

Tabula Muris Consortium; Single-cell transcriptomics of 20 mouse organs create a Tabula Muris. Nature, 562(7727): 367-372 (2018). Pubmed

Lu, W.J., Mann, R.K., Nguyen, A., Silverstein, M., Tang, J.Y., Chen, X., Beachy, P.A.  Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration. PNAS 115(2):E200-E209 (2018). Pubmed

Myers, B.R., Neahring, L., Zhang, Y., Roberts, K.J., Beachy, P.A.  Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium. PNAS 114(52):E11141-E11150 (2017). Pubmed 

See commentary: Blassberg, R., Briscoe, J.  Smoothened Sensor Places Sodium and Sterols Center Stage. Dev Cell 44(1):3-4 (2018). Pubmed

Hsia, E.Y.C., Zhang, Y., Tran, H.S., Lim, A., Chou, Y.H., Lan, G., Beachy, P.A., Zheng, X. Hedgehog mediated degradation of Ihog adhesion proteins modulates cell segregation in Drosophila wing imaginal discs. Nat Commun, 8(1):1275 (2017). Pubmed

Zhao, C., Cai, S., Shin, K., Lim, A., Kalisky, T., Lu, W-J., Clarke, M.F., Beachy, P.A. Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells. Science, 356(6335): eaal3485 (2017).   Pubmed

Lee, J.J., Rothenberg, M.E., Seeley, E.S., Zimdahl, B., Kawano, S., Lu,  W.-J., Shin, K., Sakata-Kato, T., Chen, J.K., Diehn, M., Clarke, M.F., Beachy, P.A. Control of inflammation by stromal Hedgehog pathway activity restrains colitis. Proc Natl Acad Sci, 113(47):E7545-53 (2016).   Pubmed

Sever, N., Mann, R.K., Xu, L., Snell, W.J., Hernandez-Lara, C.I., Porter, N.A., Beachy, P.A. Endogenous B-ring oxysterols inhibit the Hedgehog component Smoothened in a manner distinct from cyclopamine or side-chain oxysterols. Proc Natl Acad Sci 113(21):5904-9 (2016).   Pubmed

Kim, J., Hsia, E., Brigui, A., Plessis, A., Beachy, P.A.* Zheng, X.*  The role of ciliary trafficking in Hedgehog receptor signalings. Science Signaling 8:379 (2015). Pubmed

Shin, K., Lim, A., Zhao, C., Sahoo, D., Pan, Y., Spiekerkoetter, E., Liao, J.C., Beachy, P.A. Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 26:4:521-533 (2014). Pubmed

Lee, J.J., Perera, R.M., Wang, H., Wu, D.C., Liu, X.S., Han, S., Fitamant, J., Jones, P.D., Ghanta, K.S., Kawano, S., Nagle, J.M., Deshpande, V., Boucher, Y., Kato, T., Chen, J.K., Willmann, J.K., Bardeesy, N., Beachy, P.A. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci 111(30):E3091-100 (2014). Pubmed

Shin, K., Lim, A., Odegaard, J.I., Honeycutt J.D., Kawano, S., Hsieh, M.H., Beachy, P.A. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma.  Nat Cell Biol. 16(5):469-78 (2014). PMC4196946. Pubmed

Lim, A., Shin, K., Zhao, C., Kawano, S., Beachy, P.A. Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate. Nat Cell Biol. 16(12):1135-45 (2014). PMC4327780 Pubmed

Kim, J., Aftab, BT., Tang, J.Y., Kim, D., Lee, A.H., Rezaee, M., Kim, J., Chen, B., King, E.M., Borodovsky, A., Riggins, G.J., Epstein Jr., E.H., *Beachy, P.A., *Rudin, C.M. *Corresponding authors. Itraconazole and arsenic trioxide inhibit hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell 14:23(1):23-34 (2013). PMC3548977. Pubmed

Creanga, A., Glenn, T.D., Mann, R.K., Saunders, A.M., Talbot, W.S., Beachy, P.A. Scube/You activity mediates release of dually lipid-modified Hedgheog signal in soluble form. Genes & Dev. 26(12):1312-25 (2012). Pubmed

Shin, K., Lee, J., Guo, N., Kim, J., Qu, L., Mysorekar, I., Beachy, P.A. Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472:110-4 (2011). PMC3676169. Pubmed

Zheng, X., Mann, R., Sever, N., Beachy, P.A. Genetic and biochemical definition of the Hedgehog receptor. Genes & Development 24:57-71 (2010). PMC2802192. Pubmed

Kim, J., Tang, J., Gong, R., Kim, J., Lee, J.J., Clemons, K.V., Chong, C.R., Chang, K.S., Fereshteh, M., Gardner, D., Reya, T., Liu, J.O., Epstein, E.H., Stevens, D.A., Beachy, P.A. Itraconazole, a commonly used anti-fungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 17: 388-399 (2010). PMC4039177. Pubmed

Yao, S., Lum, L., Beachy, P.A.  The Ihog cell surface proteins bind Hedgehog and mediate pathway activation.  Cell 125:343-357 (2006). Pubmed

Cooper, M.K., Wassif, C.A., Krakowiak, P.A., Taipale, J., Gong, R., Kelley, R.I., Porter, F.D.,  Beachy, P.A.  A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis.  Nat Genet 33(4):508-13  (2003). Pubmed

Taipale, J., Cooper, M.K., Maiti, T., Beachy, P.A. Patched acts catalytically to suppress the activity of Smoothened.  Nature 418:892-896  (2002). Pubmed

Ma, Y., Erkner, A., Gong, R., Yao, S., Taipale, J., Basler, K., Beachy, P.A. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of Dispatched.  Cell 111(1):63-75 (2002). Pubmed

Chen, J.K., Taipale, J., Cooper, M.K., Beachy, P.A.  Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened.  Genes & Dev. 16: 2743-2748  (2002). Pubmed

Chen, J.K., Taipale, J., Young, K.E., Maiti, T., Beachy, P.A.  Small molecule modulation of Smoothened activity.  Proc Natl Acad Sci 99(22):14071-6  (2002).  Pubmed

Berman, D.M., Karhadkar, S.S., Hallahan, A.R., Pritchard, J.I., Eberhart, C.G., Watkins, D.N., Chen, J.K., Cooper, M.K., Taipale, J., Olson, J.M., Beachy, P.A. Medulloblastoma growth inhibition by Hedgehog pathway blockade.  Science 297(5586):1559-61 (2002). Pubmed

Chamoun, Z., Mann, R.K., Nellen, D., von Kessler, D.P., Bellotto, M., Beachy, P.A., Basler, K. Skinny Hedgehog, an acyltransferase required for palmitoylation and activity of the Hedgehog signal.  Science 293(5537):2080-4 (2001). Pubmed

Taipale, J., Chen, J.K., Cooper, M.K., Wang, B., Mann, R.K., Milenkovic, L., Scott, M.P., Beachy, P.A. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.  Nature 406:1005-1009  (2000). Pubmed

Fuse, N., Maiti, T., Wang, B., Porter, J.A., Hall, T.M., Leahy, D.J., Beachy, P.A. Sonic Hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched.  Proc Natl Acad Sci 96(20):10992-9 (1999). Pubmed

Cooper, M.K., Porter, J.A., Young, K.E., Beachy, P.A.  Teratogen-mediated inhibition of target tissue response to Shh signaling.  Science 280:1603-1607 (1998). Pubmed

Porter, J.A., Young, K.E., Beachy, P.A.  Cholesterol modification of Hedgehog signaling proteins in animal development.  Science 274:255-259 (1996). Pubmed

Chiang, C., Litingtung, Y., Lee, E., Young, K.E., Corden, J.L.,Westphal, H., Beachy, P.A.  Cyclopia and defective axial patterning in mice lacking Sonic Hedgehog gene function.  Nature 383:407-413  (1996). Pubmed

Lee, J.J., von Kessler, D.P., Parks, S., and Beachy, P.A.  Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene Hedgehog.  Cell 71:33-50  (1992). Pubmed

Select Reviews:

Roberts, K.J., Kershner, A.M., Beachy, P.A. The Stromal Niche for Epithelial Stem Cells: A Template for Regeneration and a Brake on Malignancy. Cancer Cell, 32(4):404-410 (2017).  Pubmed

Beachy, P.A., Hymowitz, S.G., Lazarus, R.A., Leahy, D.J., Siebold, C. Interactions between Hedgehog proteins and their binding partners come into view. Genes & Dev, 24(18):2001-12 (2010). Pubmed

Lum, L., Beachy, P.A.  The Hedgehog response network: sensors, switches and routers.  Science 304:1755-1759 (2004). Pubmed

Mann, R.K. and Beachy, P.A. Novel lipid modifications of secreted protein signals.  Ann. Rev. Biochem. 73:891-923 (2004). Pubmed

Taipale, J. and Beachy, P.A. The Hedgehog and Wnt signalling pathways in cancer.  Nature, 411:349-354  (2001). Pubmed