Karlyne M. Reilly, Ph.D.
Dr. Reilly received her Ph.D. in molecular and cellular biology from Harvard University and trained as a post-doctoral fellow at the Center for Cancer Research of MIT, where she held fellowships from the Leukemia & Lymphoma Society, the AACR-Sidney Kimmel Foundation, and the American Cancer Society. She came to the CCR in 2002 and established the Genetic Modifiers of Tumorigenesis Group. In 2016, she was appointed director of the Rare Tumors Initiative. Her research focuses on mechanisms of susceptibility to nervous system tumors and preclinical models of tumors associated with neurofibromatosis type 1 (NF1).
1) neurofibromatosis, 2) nervous system tumors, 3) mouse models of cancer,
4) sex differences in cancer
Developing New Preclinical Models and Testing Candidate Therapies for MPNST
Malignant peripheral nerve sheath tumors (MPNST) are one of the deadliest sarcomas and are at an increased incidence in neurofibromatosis type 1 (NF1). In the setting of NF1, MPNSTs arise through transformation of an existing benign plexiform neurofibroma (PNF), making early detection of the cancer challenging. We are working to better model and understand this transition from PNF to MPNST by 1) improving culture conditions of patient PNF cells to allow better modeling in vitro (with support from the Neurofibromatosis Therapeutic Acceleration Program), 2) developing mouse models of the transition from PNF to MPNST using information on the order in which mutations accumulate as MPNSTs form, and 3) using panels of both mouse and human MPNST cell lines to test candidate therapeutics and study underlying pathways driving MPNST growth.
Sex-specific Mechanisms of Tumorigenesis in Astrocytoma and Glioblastoma
Glial tumors, more specifically diffuse astrocytoma and glioblastoma, are the most common primary central nervous system tumors in adults and are currently incurable. Both anaplastic astrocytoma and glioblastoma are more common in males, but the biological basis of this sex difference is not understood. We hypothesize that a difference in the biology of the brain in males and females underlies the difference in susceptibility and, furthermore, could lead to sex-specific treatments for brain cancer. With support from the Congressionally Directed Medical Research Program in Neurofibromatosis, we are studying the biology of sex-specific modifiers of tumorigenesis and their normal role in the brain.
The Rare Tumor Initiative
Rare tumors are defined as affecting less than 40,000 new patients each year, or less than 200,000 patients overall in the U.S. Although individual tumor types are rare, taken together rare tumors account for 27% of all cancers diagnosed and lead to 25% of cancer-related deaths. All pediatric tumors, nervous system tumors, and sarcomas are rare. Research on rare tumors is difficult due to the low number of patients affected, and thus many rare tumors lack effective treatment options. The Rare Tumor Initiative (RTI) is working to reduce barriers and address the challenges of CCR investigators studying rare tumors and developing new therapies. The RTI is particularly focused on improving opportunities for basic-clinical collaborations to promote the “bench-to-bedside-and-back” paradigm of cancer research.
Selected Recent Publications
The Rare Tumor Initiative in the National Cancer Institute: Harnessing expertise and existing resources to develop therapies for rare tumors.Oncology Central. epub - Feb. 26, 2016. [ Journal Article ]
Developing therapies for rare tumors: opportunities, challenges and progress.Expert Opin Orphan Drugs. 4(1): 93-103, 2016. [ Journal Article ]
M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma.Neuro Oncol. [Epub ahead of print - Mar. 8]: 2016. [ Journal Article ]
Deguelins, Natural Product Modulators of NF1-Defective Astrocytoma Cell Growth Identified by High-Throughput Screening of Partially Purified Natural Product Extracts.J Nat Prod. 78(11): 2776-81, 2015. [ Journal Article ]
Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.Clin Cancer Res. 21(18): 4201-11, 2015. [ Journal Article ]
Dr. Reilly received her Ph.D. in molecular and cellular biology from Harvard University under Dr. Douglas Melton studying mesoderm induction and axis formation in Xenopus laevis. She trained as a post-doctoral fellow at the Center for Cancer Research of MIT, under Dr. Tyler Jacks, where she held fellowships from the Leukemia & Lymphoma Society, the AACR-Sidney Kimmel Foundation, and the American Cancer Society. As a post-doctoral fellow, she studied genetic modifiers of cancers associated with neurofibromatosis type 1 and characterized the first mouse model of astrocytoma and glioblastoma generated through tumor suppressor mutation. She came to the CCR in 2002 and established the Genetic Modifiers of Tumorigenesis Group where she continued her work on modifiers of nervous system tumorigenesis, identifying genetic loci affecting astrocytoma/glioblastoma, spinal astrocytoma, and malignant peripheral nerve sheath tumors. In 2016, she was appointed director of the Rare Tumor Initiative. Her current research focuses on mechanisms of susceptibility to nervous system tumors and preclinical models of tumors associated with neurofibromatosis type 1 (NF1).
|Robert Tuskan M.S.||Biologist|
|Souvik Karmakar Ph.D.||Postdoctoral Fellow (Visiting)|
|Impana Shetty||Postbaccalaureate Fellow (CRTA)|