"I am a computational biologist, and I collaborate with cancer biologists at UCSF in order to integrate computational and experimental approaches in brain cancer research. The Sontag Foundation's generous support will have a tremendous impact on my career development. This award will help me firmly establish my lab and carry out the proposed project."
- Dr. Jun Song
- Founder Professor of Bioengineering and of Physics, University of Illinois at Urbana-Champaign
About DSA-Funded Research
Human DNA is not naked, but compacted into a protein-bound three-dimensional structure called chromatin. Chemical modifications of chromatin and DNA comprise what we call the epigenome of a cell type. Cell type-specific epigenome critically regulates gene expression, and aberrant epigenetic changes are rapidly emerging as key pathogenic mechanisms in numerous diseases, including brain cancers. The recent upsurge of interest in epigenetics largely stems from the power of Next-Generation DNA Sequencing (NGS) technology which can map epigenetically modified regions. NGS is quickly reshaping the practice and methodology of cancer research. As the sequencing cost continues to drop computational analysis and correct interpretation of massive NGS data have become one of the most serious bottlenecks in biomedical research. In particular, identifying epigenetic signatures predictive of prognostic outcomes and treatment response requires sequencing multiple patient samples. Unfortunately, we currently do not understand how to properly normalize multiple NGS data together, and how to quantify the biologically meaningful differences in the epigenomes of cancer vs. normal in case-control studies or cancer vs. cancer in time-course cancer progression models. This project thus proposes to develop rigorous computational methods for (1) removing sequencing artifacts and normalizing multiple NGS samples, (2) quantifying aberrant epigenetic changes between samples, and (3) modeling the time-course evolution of brain cancer epigenomes and discovering how epigenetic changes are coupled to gene expression alterations during brain cancer progression. The results of our research will contribute towards identifying novel epigenetic factors which may be targeted to prevent malignant transformation and treat brain cancer patients.
"Jun has transformed himself from a mathematical physicist into a creative and independent computational genomics and gene regulation expert. He is the most motivated and hardworking scientist I have ever known."
Xiaole Shirley Liu, Ph.D.
Dana-Farber Cancer Institute
"Jun is very focused, motivated and productive. His understanding of biology and his taste and choice of research problems are all excellent. He is very smart and quickly sees and follows the implications of his results and analysis."
Arnold J. Levine, Ph.D.
Institute for Advanced Study
- Collaboration with Anna Krichevsky on the role of miRNAs in GBM.
- Collaboration with Dan Lim on ChIP-seq analysis and lncRNAs in neural stem cells.
- Susan Chang is a co-author on several of my papers.
- A. Diaz, K.-Y. Park, D.A. Lim, and J.S. Song. Normalization, bias correction, and peak calling for ChIP-seq, Statistical Applications in Genetics and Molecular Biology, Vol 11: Iss. 3, Article 9, (2012).
- A. Diaz, A. Nellore, J.S. Song. CHANCE - CHip-seq ANalytics and Confidence Estimation: comprehensive software for quality control and validation of ChIP-seq data, Genome Biology 13:R98, (2012).
- A.D. Ramos, A. Diaz, A. Nellore, R.N. Delgado, K.-Y. Park, G. Gonzales-Roybal, M.C. Oldham, J.S. Song, D.A. Lim. Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo. Cell Stem Cell 12, 616-628, (2013).
- B.E. Johnson, T. Mazor, et al. Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma, Science, 343(6167), 189-93, (2014).
- H. Qin1, A. Diaz1, L. Blouin, R.J. Lebbink, W. Patena, P. Tanbun, E.M. LeProust, M.T. McManus2, J.S. Song2,*, M. Ramalho-Santos2,* (1co-first authors, 2co-senior authors, *co-corresponding authors). Systematic Identification of Barriers to Human iPSC Generation, Cell, 158(2), 449-461, (2014).
- R.P. Nagarajan , B. Zhang, R.J. Bell, B.E. Johnson, A.B. Olshen, V. Sundaram, D. Li, A.E. Graham, A. Diaz, S.D Fouse, I. Smirnov, J. Song, P.L. Paris, T. Wang, J.F. Costello, Recurrent epimutations activate gene body promoters in primary glioblastoma. Genome Research, 24(5), 761-74, (2014).
- Chen J, Hackett CS, Zhang S, Song YK, Bell RJA, Molinaro AM, Quigley DA, Balmain A, Song JS, Costello JF, Gustafson WC, Van Dyke T, Kwok PY, Khan J, Weiss WA. The genetics of splicing in neuroblastoma. Cancer Discovery, 5(4), 380-95, (2015).
- M. Guzman-Ayala, M. Sachs, F.M. Koh, C. Onodera, A. Bulut-Karslioglu, C.J. Lin, P. Wong, R. Nitta, J.S. Song, and M. Ramalho-Santos. Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast, Development, 142(1), 118-27, (2015).
- A. Diaz1, H. Qin1, M. Ramalho-Santos*, J.S. Song* (1co-first authors, *co-corresponding authors). HiTSelect: A Comprehensive Tool for High-Complexity Pooled Screen Analysis, Nucleic Acids Research, 43(3):e16, (2015).
- T. Mazor1, A. Pankov1, B.E. Johnson, C. Hong, E.G. Hamilton, R.J.A. Bell, I.V. Smirnov, G.F. Reis, J.J. Phillips, M.J. Barnes, A. Idbaih, A. Alentorn, J.J. Kloezeman, M.L.M. Lamfers, A.W. Bollen, B.S. Taylor, A.M. Molinaro, A.B. Olshen, S.M. Chang, J.S. Song,2,* and J.F. Costello2,*. (1co-first authors, 2co-senior authors, *co-corresponding authors). DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors, Cancer Cell, 28(3), 307-317, (2015)
- R.J.A. Bell, H.T. Rube, A. Kreig, A. Mancini, S.D. Fouse, R.P. Nagarajan, S. Choi, C. Hong, D. He, M. Pekmezci, J.K. Wiencke, M.R. Wrensch, S.M. Chang, K.M. Walsh, S. Myong, J.S. Song*,# and J.F. Costello*,#. (*co-corresponding authors, #equal contribution). The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer, Science, 348, 1036-1039, (2015).
- H.A. Wong, R.E. Fatimy, C. Onodera, Z. Wei, M. Yi, A. Mohan, S. Gowrisankaran, P. Karmali, E. Marcusson, H. Wakimoto, R. Stephens, E.J. Uhlmann, J.S. Song, B. Tannous and A.M. Krichevsky. TCGA analysis predicts microRNA for targeting cancer growth and vascularization in glioblastoma, Molecular Therapy, 23(7), 1234-47, (2015).
- T. Mazor1, A. Pankov1, J.S. Song, J.F. Costello (1co-first authors). Intratumoral Heterogeneity of the Epigenome. Cancer Cell, 29, 440-451, (2016).
- R.J.A. Bell, H.T. Rube, A. Xavier-Magalhaes, B.M. Costa, A. Mancini, J.S. Song, J.F. Costello. Understanding TERT Promoter Mutations: a Common Path to Immortality. Molecular Cancer Research, 14(4), 315-23, (2016).