- 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)
- Park T-J, Curran T. Essential roles of Crk and CrkL in fibroblast structure and motility.. Oncogene. 2013 Oct.
- Gajjar Amar, Stewart Clinton F, Ellison David W, Kaste Sue, Kun Larry E, Packer Roger J, Goldman Stewart, Chintagumpala Murali, Wallace Dana, Takebe Naoko, Boyett James M, Gilbertson Richard J, Curran Tom. Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study.. Clinical cancer research : an official journal of the American Association for Cancer Research. 2013 Oct.
- Wang Yu, Davidow Lance, Arvanites Anthony C, Blanchard Joel, Lam Kelvin, Xu Ke, Oza Vatsal, Yoo Jin Woo, Ng Jessica M Y, Curran Tom, Rubin Lee L, McMahon Andrew P. Glucocorticoid compounds modify smoothened localization and hedgehog pathway activity.. Chemistry & biology. Vol 19(8) . 2012 Aug:972-82.
- George Britta, Verma Rakesh, Soofi Abdulsalam A, Garg Puneet, Zhang Jidong, Park Tae-Ju, Giardino Laura, Ryzhova Larisa, Johnstone Duncan B, Wong Hetty, Nihalani Deepak, Salant David J, Hanks Steven K, Curran Tom, Rastaldi Maria Pia, Holzman Lawrence B. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease.. The Journal of Clinical Investigation. Vol 122(2) . 2012 February:674-692.
- Curran Tom. Q&A: Tom Curran on translational research.. Cancer Discovery. Vol 2(2) . 2012 Feb:99.