Candidate Upon graduating with a Ph.D. from the integrative biology department of the University of Texas Southwestern Medical Center, I pursued a post-doctoral position in the lab or Dr. Soo-Kyoung Lee at Baylor College of Medicine (Houston, TX), during which I studied the transcriptional programs that orchestrate the expression of axon guidance factors in the developing spinal cord. My work in the Lee lab was supported by the supplemental grant for underrepresented minorities from the NIH. To move my career trajectory toward a more translational area of study, I undertook a second post-doctoral position in the laboratory of Dr. Deneen at Baylor College of Medicine, where I have worked for three years. I am now applying for more senior fellowships/awards and beginning to take the initial steps toward establishing my own research program. My current work is driven by an interest in combining my skills and expertise in developmental biology with disease-based models of tumorigenesis. Obtaining the NCI Mentored Research Scientist Development Award (K01) will allow me to gain both the additional conceptual/ technical training and pursue the career development activities I have outlined in this application such as, journal clubs, seminars, and conferences. With this additional training I will be able to pursue an independent research position at a highly ranked institution. My overall career goal is to initiate and sustain a successful research career in glial lineage development and transcriptional regulation of gliomagenesis. My goals for the mentored career award include publishing three first-author papers in high-impact journals; learn concepts and research techniques in the area of cancer biology; and to complete the career development activities that will launch my independent research program and funding. I hope to make a significant contribution to the understanding of glial cell biology and glioma tumorigenesis with the ultimate goal of translational application. Environment Baylor College of Medicine (BCM) is a premier research institution with a strong commitment to research and finding new treatments and cures for disease. As a part of the Cell and Gene Therapy (CAGT), and Stem Cells and Regenerative Medicine Center (STaR), I will have access to a large array of equipment and a wide range of core facilities with expertise in Flow Cytometry and genomic/RNA profiling. The CAGT and STaR centers have a long history of translational research; faculty have a diverse range of interests including immunotherapy and stem cell biology. The centers encourage interaction and collaboration among its members which provides a rich environment for my additional scientific training. The CAGT is particularly well suited for studying gliomagenesis as several faculty members with specific expertise in glioma biology and immunotherapy approaches to brain tumors have committed to supporting my proposed project. Research During my time in the Deneen lab I have studied the transcriptional regulation of developmental gliogenesis and have begun to translate these developmental concepts to the study of glioma. I have identified a transcriptional cascade consisting of two transcription factors, Sox9 and NFIA, which orchestrate the initiation of gliogenesis in the developing spinal cord. Furthermore, I have found transcriptional functions for NFIA in oligodendrocytes and multiple sclerosis. Currently, I am examining the Sox9/NFIA relationship in more detail and hypothesize that the developmental relationship between Sox9 and NFIA is maintained during gliomagenesis. The experiments proposed here are geared toward examining this relationship in malignant glioma. I utilize a highly innovative and novel mouse model of glioma which rapidly generates (within 3 weeks) malignant gliomas, combined with complementary studies in primary human glioma cell lines to study the roles of NFIA and Sox9 in glioma tumorigenesis. The importance of transcriptional regulation of developmental determining factors in glioma tumorigenesis is just beginning to be explored. My proposed transcriptional profiling experiments in malignant gliomas using a combination of ChIP-seq and gene expression profiling technologies will serve as a platform for studying the relationship between developmental programs and gliomagenesis. I believe that the research outlined in this project can contribute to the fundamental understanding of gliogenesis and glioma tumorigenesis and will have relevance to human gliomas.
Glioma is the most prevalent form of adult brain cancer and has an extremely poor prognosis. The work proposed will define transcriptional networks which regulate glioma sub-type and tumorigenesis and begin to address some of the fundamental issues that have hampered the progress toward identifying new treatments of this deadly disease.
| Glasgow, Stacey M; Carlson, Jeffrey C; Zhu, Wenyi et al. (2017) Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis. Nat Neurosci 20:1520-1528 |
