Studying a novel regulator of GBM tumorigeneis: the role of CK2alpha in maintaini

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DESCRIPTION (provided by applicant): I completed my neurosurgery residency in June of 2011 and was subsequently hired as Assistant Professor of Neurosurgery at Stanford University. My immediate career goals include building a laboratory dedicated to understanding the biology of malignant gliomas and translating this work to clinical trials. In the near term, wih the mentorship and support of Dr. Albert Wong and the Department of Neurosurgery, I will advance my knowledge of laboratory techniques, learn to manage a laboratory, teach and mentor in a structured environment, further develop my ability to critically ask and answer scientific questions, refine my grant writing skills, and troubleshoot projects. My goal is to transition to independence by the conclusion of this project. I have received significant support from Stanford, including laboratory space and 50% dedicated time towards research, as well as startup funds and research personnel to carry out the proposed project. My location two floors above my mentor, Dr. Wong, and next door to the Department of Neurosurgery laboratories will facilitate active mentoring and growth during the grant period. Dr. Wong and I will meet at least weekly to discuss any questions that may arise. Dr. Wong has a long history of translating projects to clinical trials and has been involved in many clinical trials. Moreover, to supplement my mentorship and guidance, I will take full advantage of the rich resources available at Stanford University, including conferences, forums, programs and classes designed to help young investigators develop and grow. I will also attend national and international meetings, including the Society for Neuro-Oncology, American Association for Cancer Research, Cold Spring Harbor Laboratory on Cancer Biology and Therapeutics, and Keystone Symposia meetings. Importantly, my laboratory and offices are adjacent to the laboratory of Dr. Gary Steinberg. He is an exemplary example of a successful surgeon-scientist and is a tremendous role model to whom I can look for guidance. Dr. Steinberg is the Chairman of the Department of Neurosurgery as well as Director of the Stanford Institute for Neuro- Innovation and Translational Neurosciences (SINTN). He has successfully built a busy clinical practice as well as run a large NIH-funded laboratory studying the implantation of stem cells for the treatment of stroke. I will meet with him on a monthly basis. I have additionally organized an independent committee to oversee my development and path towards independence. This committee includes Dr. Gary Steinberg, Dr. Keith Black- a respected surgeon-scientist, Chairman of Neurosurgery at Cedar Sinai Medical Center and an expert on brain tumor therapies and the blood-brain barrier-and Dr. Irv Weissman-the Director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University and a leader in the field of stem cell research who has vast experience with antibody approaches for the treatment of cancer. My research project stems from preliminary data performed in my laboratory, independent of my mentor, since commencing my laboratory in October of 2011. My studies focus on the role of casein kinase 2 (CK2), a highly conserved pleiotropic serine/threonine kinase that has been associated with cell survival in many cancers. There is direct evidence demonstrating that enhanced expression or activity of the catalytic subunit CK2α plays an important role in glioblastoma (GBM) tumor genesis. Data from my laboratory indicate a novel function in which CK2α regulates pathways necessary for GBM cancer stem cell growth. The goals of my proposed research project are to elucidate the role of CK2α in GBM cancer stem cell maintenance and growth, to study the mechanism of activation of CK2α in GBM tumor genesis, and to develop strategies to target CK2α in GBM cancer stem cells using an intracranial mouse model. My hypothesis is that CK2α is important in maintaining GBM cancer stem cells through the regulation of signaling cascades such as Wingless/Int. (WNT) and Sonic Hedgehog (SHH). Therefore, by targeting CK2α I hope to elucidate a novel GBM therapeutic target that will eliminate the cancer stem cells that promote growth and formation of GBMs. Obtaining K08 funding is crucial to my development as an independent clinician-investigator, providing the necessary protected time and structured mentoring required to develop my research program. Stanford has equipped me with all the necessary mentoring, didactics, and resources as well as the ideal environment to grow as a scientist and to evolve into an independent investigator. My long term goals are to be a leader in a comprehensive brain tumor center at Stanford where discoveries in the laboratory translate to clinical therapeutics trials, and to join Stanford's nationally recognized surgical neuro-oncology group. Supported by a long history of collaboration with other clinical and scientific departments, I am inspired to excel in this optimal environment, replete with rich resources to achieve my goals, and honored to begin my career here.