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Search Results to Jessie Ng

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keywords Targeted Therapy
research overview Dr. Jessie Ng is working to develop better treatments for the aggressive brain tumors medulloblastoma (MB) and atypical teratoid rhabdoid tumor (AT/RT). Over the past several years, Dr. Ng and coworkers in Dr. Curran’s lab helped develop a new approach to the treatment of MB using Hedgehog (Hh) pathway inhibitors. The lab conducted molecular gene expression studies that identified four major subtypes of MB tumors and developed a mouse model (Ptc1/p53) for high-incidence, early-onset Hh subtype MB. Using this spontaneous central nervous system (CNS) mouse model, they demonstrated that oral delivery of small molecule inhibitors of Smoothened (Smo), called GDC-0449 or vismodegib, eliminated even large spontaneous brain tumors in mice. They worked with Curis Inc., and later Genentech Inc., to demonstrate proof-of-concept of the use of Hh inhibitors in cancer. This work led to successful Phase I and II clinical trials of Smo inhibitors in pediatric and adult MB that recapitulated all the major findings obtained in mice. Because of these efforts, the first Smo inhibitor (vismodegib) was approved for treatment of advanced basal cell carcinoma in 2012. The next step is to focus on targeting drug-resistant brain tumors. Dr. Ng will use in vitro high-throughput drug screening as well as noninvasive imaging approaches (such as MRI and CT), drug delivery therapies and next-generation sequencing. The ultimate goal of the research is to develop new drugs for clinical trials in pediatric brain cancer. Dr. Ng’s research is also investigating the role of INI1 (Integrase Interactor 1), also known as SNF5 or SMARCB1. SNF5 is a key component of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling tumor suppressor complex, which is an ATP-dependent nucleosome-remodeling complex that regulates gene transcription in CNS development and tumorigenesis, including the pediatric CNS tumor AT/RT. Dr. Ng has generated the first CNS mouse model for AT/RT, which is quite crucial because with this model they can now test potential drugs in vivo and investigate the cell of origin to understand the cancer biology of AT/RT.

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  • Experimental
  • Therapeutics