Yael P Mosse, M.D.

faculty photo
Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
Colket Translational Research Building, Office 3056
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-590-0965
Fax: 267-426-0685
Hebrew University, Jerusalem, Israel, 1992.
Smith College, 1993.
Sackler School of Medicine, Tel Aviv, Israel, 1997.
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Description of Research Expertise

Despite major enhancements in therapy over the past several decades, the cure rate for patients with high-risk neuroblastoma lags significantly behind that of other childhood cancers. My lab has unwaveringly focused on neuroblastoma and on the hypothesis that discovery of its hereditary basis will provide insights that are clinically actionable and improve outcomes. Our seminal discovery that gain-of-function mutations in the Anaplastic Lymphoma Kinase (ALK) oncogene are the cause of familial neuroblastoma (Nature, 2008) highlights the insights gained from a family-based study in a rare disease and the opportunities for targeting ALK in neuroblastoma and other human cancers driven by ALK. We have led collaborative investigations that demonstrated frequent ALK activating mutations in the more common sporadic cases, the development of molecular diagnostic tools, and preclinical studies to establish the role of ALK inhibitors in the treatment of neuroblastoma and other childhood cancers. This work led to the completion of a multi-institutional pediatric phase 1 trial of crizotinib (The Lancet Oncology, 2013), demonstrating rapid translation of preclinical molecular findings into the clinic. We have positioned ALK as the only mutated oncogene tractable for targeted therapy in neuroblastoma and subsequently showed that there is differential mutation-specific sensitivity to crizotinib that results from a relative increase in ATP-binding affinity (Science Translational Medicine, 2011), data that directly impacted the design of the pediatric phase 1 trial. Additionally, we have shown that ALK is a tractable target for immunotherapy (Oncogene, 2012), setting the stage for the development of antagonistic antibodies to maximize clinical benefit.

Description of Clinical Expertise

I am a physician-scientist focused on neuroblastoma who is committed to making basic science discoveries in this disease and translating them immediately to the clinic . We made the seminal discovery that activating mutations in the ALK oncogene are the major cause of hereditary neuroblastoma, and that somatically acquired ALK mutations often drive the malignant process in sporadic tumors. We thus established ALK as a tractable molecular target in neuroblastoma, and rapidly initiated a now-completed phase 1 trial (and ongoing phase 2 trial) of the ALK inhibitor crizotinib. We have therefore succeeded in bench-to-bedside translation of our own novel cancer genetic discovery. We are proud that this translation has been remarkably rapid, and that it has changed the field. As a physician-scientist who co-leads one of the world’s largest developmental therapeutics program for children with refractory neuroblastoma, I recognize the challenges with this disease, and appreciate the difference that having therapeutic targets makes. To further this development, I have forged a team effort that brings together key expertise in translational genomics, biochemistry, bioengineering and pharmacology, with the common goal of improving cure rates. We are well positioned to provide novel insights into neuroblastoma tumorigenesis that will enable development of rational and effective ALK-inhibition strategies. These will result in translational opportunities impacting patients with neuroblastoma as well as histologically diverse tumors where ALK is a critical mediator of oncogenesis. Motivated by our successes with ALK, we are also committed to identifying additional new therapeutic approaches in a devastating human condition.

Selected Publications

Mossé Yaël P, Laudenslager Marci, Longo Luca, Cole Kristina A, Wood Andrew, Attiyeh Edward F, Laquaglia Michael J, Sennett Rachel, Lynch Jill E, Perri Patrizia, Laureys Geneviève, Speleman Frank, Kim Cecilia, Hou Cuiping, Hakonarson Hakon, Torkamani Ali, Schork Nicholas J, Brodeur Garrett M, Tonini Gian P, Rappaport Eric, Devoto Marcella, Maris John M: Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455(7215): 930-5, Oct 2008.

Bresler Scott C, Wood Andrew C, Haglund Elizabeth A, Courtright Joshua, Belcastro Lili T, Plegaria Jefferson S, Cole Kristina, Toporovskaya Yana, Zhao Huaqing, Carpenter Erica L, Christensen James G, Maris John M, Lemmon Mark A, Mossé Yaël P: Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Science Translational Medicine 3(108): 108ra114, Nov 2011.

Mosse Yael P, Lim Megan S, Voss Stephan D, Wilner Keith, Ruffner Katherine, Laliberte Julie, Rolland Delphine, Balis Frank M, Maris John M, Weigel Brenda J, Ingle Ashish M, Ahern Charlotte, Adamson Peter C, Blaney Susan M: Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. The lancet oncology 14(6): 472-80, May 2013.

Carpenter E L, Haglund E A, Mace E M, Deng D, Martinez D, Wood A C, Chow A K, Weiser D A, Belcastro L T, Winter C, Bresler S C, Asgharzadeh S, Seeger R C, Zhao H, Guo R, Christensen J G, Orange J S, Pawel B R, Lemmon M A, Mosse Y P: Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma. Oncogene 31(46): 4859-67, Nov 2012.

Mosse Yael P, Lipsitz Emily, Fox Elizabeth, Teachey David T, Maris John M, Weigel Brenda, Adamson Peter C, Ingle Mark A, Ahern Charlotte H, Blaney Susan M: Pediatric Phase I Trial and Pharmacokinetic Study of MLN8237, an Investigational Oral Selective Small-Molecule Inhibitor of Aurora Kinase A: A Children's Oncology Group Phase I Consortium Study. Clinical Cancer Research 18(21): 6058-64, Nov 2012.

Carpenter Erica L, Mossé Yael P: Targeting ALK in neuroblastoma--preclinical and clinical advancements. Nature Reviews Clinical Oncology 9(7): 391-9, Jul 2012.

Pugh Trevor J, Morozova Olena, Attiyeh Edward F, Asgharzadeh Shahab, Wei Jun S, Auclair Daniel, Carter Scott L, Cibulskis Kristian, Hanna Megan, Kiezun Adam, Kim Jaegil, Lawrence Michael S, Lichenstein Lee, McKenna Aaron, Pedamallu Chandra Sekhar, Ramos Alex H, Shefler Erica, Sivachenko Andrey, Sougnez Carrie, Stewart Chip, Ally Adrian, Birol Inanc, Chiu Readman, Corbett Richard D, Hirst Martin, Jackman Shaun D, Kamoh Baljit, Khodabakshi Alireza Hadj, Krzywinski Martin, Lo Allan, Moore Richard A, Mungall Karen L, Qian Jenny, Tam Angela, Thiessen Nina, Zhao Yongjun, Cole Kristina A, Diamond Maura, Diskin Sharon J, Mosse Yael P, Wood Andrew C, Ji Lingyun, Sposto Richard, Badgett Thomas, London Wendy B, Moyer Yvonne, Gastier-Foster Julie M, Smith Malcolm A, Auvil Jaime M Guidry, Gerhard Daniela S, Hogarty Michael D, Jones Steven J M, Lander Eric S, Gabriel Stacey B, Getz Gad, Seeger Robert C, Khan Javed, Marra Marco A, Meyerson Matthew, Maris John M: The genetic landscape of high-risk neuroblastoma. Nature genetics 45(3): 279-84, Mar 2013.

Maris John M, Mosse Yael P, Bradfield Jonathan P, Hou Cuiping, Monni Stefano, Scott Richard H, Asgharzadeh Shahab, Attiyeh Edward F, Diskin Sharon J, Laudenslager Marci, Winter Cynthia, Cole Kristina A, Glessner Joseph T, Kim Cecilia, Frackelton Edward C, Casalunovo Tracy, Eckert Andrew W, Capasso Mario, Rappaport Eric F, McConville Carmel, London Wendy B, Seeger Robert C, Rahman Nazneen, Devoto Marcella, Grant Struan F A, Li Hongzhe, Hakonarson Hakon: Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. The New England journal of medicine 358(24): 2585-93, Jun 2008.

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Last updated: 07/11/2022
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