J
Joseph Kelleher
Researcher at Novartis
Publications - 22
Citations - 2262
Joseph Kelleher is an academic researcher from Novartis. The author has contributed to research in topics: Smoothened & Hedgehog signaling pathway. The author has an hindex of 15, co-authored 22 publications receiving 2069 citations.
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Journal ArticleDOI
Interfering with Resistance to Smoothened Antagonists by Inhibition of the PI3K Pathway in Medulloblastoma
Silvia Buonamici,Juliet Williams,Michael Morrissey,Anlai Wang,Ribo Guo,Anthony Vattay,Kathy Hsiao,Jing Yuan,John Green,Beatriz Ospina,Qunyan Yu,Lance Ostrom,Paul Fordjour,Dustin L. Anderson,John Monahan,Joseph Kelleher,Stefan Peukert,Shifeng Pan,Xu Wu,Sauveur Michel Maira,Carlos Garcia-Echeverria,Kimberly J. Briggs,D. Neil Watkins,Yung Mae Yao,Christoph Lengauer,Markus Warmuth,William R. Sellers,Marion Dorsch +27 more
TL;DR: By identifying a drug combination that delays or even combats development of resistance when used as a first-line treatment in clinical trials, these results could ultimately improve the lives of patients with medulloblastoma or other cancers that depend on Smo for their survival.
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Essential role of stromally induced hedgehog signaling in B-cell malignancies
Christine Dierks,Christine Dierks,Jovana Grbic,Katja Zirlik,Ronak Beigi,Nathan P. Englund,Gui-Rong Guo,Hendrik Veelken,Monika Engelhardt,Roland Mertelsmann,Joseph Kelleher,Peter G. Schultz,Peter G. Schultz,Markus Warmuth +13 more
TL;DR: It is demonstrated that hedgehog ligands secreted by bone-marrow, nodal and splenic stromal cells function as survival factors for malignant lymphoma and plasmacytoma cells derived from transgenic Eμ-Myc mice or isolated from humans with these malignancies.
Journal ArticleDOI
Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist
Shifeng Pan,Xu Wu,Jiqing Jiang,Wenqi Gao,Yongqin Wan,Dai Cheng,Dong Han,Jun Liu,Nathan P. Englund,Yan Wang,Stefan Peukert,Karen Miller-Moslin,Jing Yuan,Ribo Guo,Melissa Matsumoto,Anthony Vattay,Yun Jiang,Jeffrey Tsao,Fangxian Sun,AnneMarie Culazzo Pferdekamper,Stephanie Kay Dodd,Tove Tuntland,Wieslawa Maniara,Joseph Kelleher,Yung-mae Yao,Markus Warmuth,Juliet Williams,Marion Dorsch +27 more
TL;DR: Structural-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl- 3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.
Journal ArticleDOI
Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway
Zainab Jagani,E. Lorena Mora-Blanco,Courtney G. Sansam,Elizabeth S. McKenna,Boris G. Wilson,Dongshu Chen,Justin Klekota,Pablo Tamayo,Phuong L. Nguyen,Michael Y. Tolstorukov,Peter J. Park,Yoon Jae Cho,Yoon Jae Cho,Kathy Hsiao,Silvia Buonamici,Scott L. Pomeroy,Jill P. Mesirov,Heinz Ruffner,Tewis Bouwmeester,Sarah J. Luchansky,Joshua Murtie,Joseph Kelleher,Markus Warmuth,William R. Sellers,Charles W. M. Roberts,Marion Dorsch +25 more
TL;DR: The studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells.
Journal ArticleDOI
Topical Treatment of Basal Cell Carcinomas in Nevoid Basal Cell Carcinoma Syndrome with a Smoothened Inhibitor
Hans Skvara,Frank Kalthoff,Josef G. Meingassner,Barbara Wolff-Winiski,Heinrich Aschauer,Joseph Kelleher,Xu Wu,Shifeng Pan,Lesanka Mickel,Christopher Schuster,Georg Stary,Ahmad Jalili,Olivier J. David,Corinne Emotte,Ana Antunes,Kristine Rose,Jeremy Decker,Ilene Carlson,Humphrey Gardner,Anton Stuetz,Arthur P. Bertolino,Georg Stingl,Menno A. De Rie +22 more
TL;DR: Treatment with 0.75% LDE225 cream in NBCCS patients was very well tolerated and caused BCC regression, thus potentially offering an attractive therapeutic alternative to currently available therapies for this indication.