- Administrative Units:
Core Facilities Administration,Technology Transfer,Research Safety
- Centers of Emphasis:
Childhood Cancer Research
The Curran laboratory studies brain development and pediatric brain tumors. The goal is to identify molecular changes and potential drug targets. Additional studies focus on the mechanism of action of anticancer drugs in tumor cells and cancer models.
Brain tumors, brain development, genomics.
Key words: Brain, Development, Molecular Oncology, Reelin, sonic hedgehog, neuro-oncology, oncogenes
Description of Research
Our research addresses the molecular basis of normal and neoplastic growth in the developing nervous system. We hope that by understanding the normal processes that govern formation of the brain we will uncover new approaches for the treatment of rare but very devastating pediatric brain tumors. Research in the laboratory combines basic approaches with genomics and translational science in a broad-based effort. Our experimental strategies include mouse disease models, cell culture, genomics, human tumor samples, imaging and a range of molecular techniques.
Previously, we identified the reelin gene (Reln) whose protein product is a large extracellular protein that controls cell migration and is secreted by several early populations of neurons in the developing brain. We are now examining the molecular events downstream of Reln that mediate its function. To accomplish this we are developing several conditional mutant mouse lines and we are utilizing cell and molecular biology approaches.
We are taking genomic approaches to identify molecular changes and potential drug targets for several brain tumors including medulloblastoma, atypical teratoid/rhabdoid tumors and choroid plexus carcinomas. We developed a model system with a 100 percent incidence of spontaneous medulloblastoma for use in translational studies. Recently, we found that a small molecule inhibitor of the sonic hedgehog (Shh) pathway eliminated even large tumor masses in vivo. We are continuing to analyze the mechanism of action of several anticancer drugs in tumor cells and cancer models.
Opportunities are available to investigate the response of brain tumors to molecular targeted therapies in genetic mouse models. Opportunities are also available to investigate the molecular control of cell migration in the developing brain and signaling components of the Reelin pathway. Please contact Dr. Curran for available projects.
Jessica Ng Ph.D., Tae-Ju Park Ph.D., Mateusz Koptyra Ph.D., Hanna Li, Erin Fin; Dianne Settles, Executive Assistant
- Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2006– present)
- Professor of Cell and Developmental Biology at University of Pennsylvania School of Medicine (2008 – 2011)
- PhD, Zoology and Anatomy, Imperial Cancer Research Fund Laboratories and University College London (1982)
- BSc (Hons), Zoology, University of Edinburgh (1978)
- Parsons D Williams, Li Meng, Zhang Xiaosong, Jones Siân, Leary Rebecca J, Lin Jimmy Cheng-Ho, Boca Simina M, Carter Hannah, Samayoa Josue, Bettegowda Chetan, Gallia Gary L, Jallo George I, Binder Zev A, Nikolsky Yuri, Hartigan James, Smith Doug R, Gerhard Daniela S, Fults Daniel W, Vandenberg Scott, Berger Mitchel S, Marie Suely Kazue Nagahashi, Shinjo Sueli Mieko Oba, Clara Carlos, Phillips Peter C, Minturn Jane E, Biegel Jaclyn A, Judkins Alexander R, Resnick Adam C, Storm Phillip B, Curran Tom, He Yiping, Rasheed B Ahmed, Friedman Henry S, Keir Stephen T, McLendon Roger, Northcott Paul A, Taylor Michael D, Burger Peter C, Riggins Gregory J, Karchin Rachel, Parmigiani Giovanni, Bigner Darell D, Yan Hai, Papadopoulos Nick, Vogelstein Bert, Kinzler Kenneth W, Velculescu Victor E. The Genetic Landscape of the Childhood Cancer Medulloblastoma.. Science (New York, N.Y.). Vol 331. 2010 Dec:435-439.
- Seidel Kerstin, Ahn Christina P, Lyons David, Nee Alexander, Ting Kevin, Brownell Isaac, Cao Tim, Carano Richard A D, Curran Tom, Schober Markus, Fuchs Elaine, Joyner Alexandra, Martin Gail R, de Sauvage Frederic J, Klein Ophir D. Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor.. Development (Cambridge, England). Vol 137(22) . 2010 Nov:3753-61.
- Hallock Peter T, Xu Chong-Feng, Park Tae-Ju, Neubert Thomas A, Curran Tom, Burden Steven J. Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L.. Genes & development. Vol 24(21) . 2010 Nov:2451-61.
- Park, TJ, Curran, T. Crk and Crk-Like Play Essential Overlapping Roles Downstream of Disabled-1 in the Reelin Pathway. Journal Of Neuroscience. Vol 28(50) . 2008 DEC 10:13551-13562.
- De Gasperi, R, Sosa, MAG, Wen, PH, Li, JJ, Perez, GM, Curran, T, Elder, GA. Cortical development in the presenilin-1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin-dependent signaling. Developmental Dynamics. Vol 237(9) . 2008 SEP:2405-2414.
- Kimura H, Ng JMY, Curran T.. Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure.. Cancer Cell. Vol 13. 2008:249-60.
- Sasai K., Romer JT., Kimura H., Eberhart DE., Rice DS., Curran T.. Medulloblastomas derived from Cxcr6 mutant mice respond to treatment with a smoothened inhibitor. Cancer Research. Vol 67(8) . 2007 Apr 15:3871-7.
- Ke Y, Zhang EE, Hagihara K, Wu D, Pang Y, Klein R, Curran T, Ranscht B, Feng GS.. Deletion of Shp2 in the brain leads to defective proliferation and differentiation of neural stem cells and early postnatal lethality.. Mol Cell Biol. Vol 27. 2007:6706-17.
- Lee Y, Kawagoe R, Sasai K, Li Y, Russell HR, Curran T and McKinnon PJ.. Loss of Suppressor-of-Fused function promotes tumorigenesis.. Oncogene. Vol 26. 2007:6442-7.
- Park TJ., Boyd K., Curran T.. Cardiovascular and craniofacial defects in Crk-null mice. Molecular & Cellular Biology. Vol 26(16) . 2006 Aug:6272-82.