Je H. Lee
M.D., Ph.D., Tufts School of Medicine, 2002
Cells are amazingly complex, with the ability to sense, and remember timing, location and history. I am exploring how cells store this information, and how their surroundings influence their communication with other cells. I am also developing various imaging and molecular sequencing methods for tracking genes, molecules, and cells to understand how cancer cells arise and evolve.
The Lee Lab studies how cells interact with their microenvironment to regulate gene expression during development. Single cell heterogeneity in gene expression can result from spatial differences in cell-cell and cell-extracellular matrix interactions. Such differences contribute to stochastic evolution of tumor cells as well as morphogenesis during normal development. However, the spatial control of gene expression in complex tissues, embryos, or tumors remains poorly understood, because most genome-wide studies sample bulk tissues or dissociated single cells.
We have recently developed a method to sequence RNA molecules directly within single cells and tissues using sub-cellular resolution imaging, and we demonstrated subtle differences in cell-cell/ECM signaling and gene expression genome-wide in situ. By clustering transcripts into functionally or morphological discrete regions, we find many unique spatial markers and signaling pathways. My lab focuses on the role of non-coding RNA in chromatin remodeling and tumor progression using mouse and organoid models of human cancer. We use in situ sequencing, cell lineage tracing, and single-cell profiling to understand how non-coding RNA affects tumor cell evolution in their native context. Our long-term goal is to develop better tumor classification tools and anti-cancer therapeutics using our understanding of the tumor microenvironment.
Lee, J. H. and Daugharthy, E. R. and Scheiman, J. and Kalhor, R. and Yang, J. L. and Ferrante, T. C. and Terry, R. and Jeanty, S. S. and Li, C. and Amamoto, R. and Peters, D. T. and Turczyk, B. M. and Marblestone, A. H. and Inverso, S. A. and Bernard, A. and Mali, P. and Rios, X. and Aach, J. and Church, G. M. (2014) Highly multiplexed subcellular RNA sequencing in situ. Science 343(6177) pp. 1360-3.
Mali, P. and Aach, J. and Lee, J. H. and Levner, D. and Nip, L. and Church, G. M. (2013) Barcoding cells using cell-surface programmable DNA-binding domains. Nat Methods 10(5) pp. 403-6.
Lo, C. and Liu, R. and Lee, J. and Robasky, K. and Byrne, S. and Lucchesi, C. and Aach, J. and Church, G. and Bafna, V. and Zhang, K. (2013) On the design of clone-based haplotyping. Genome Biol 14(9) pp. R100.
Lee, J. H. and Park, I. H. and Gao, Y. and Li, J. B. and Li, Z. and Daley, G. Q. and Zhang, K. and Church, G. M. (2009) A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells. PLoS Genet 5(11) pp. e1000718.Additional materials of the author at
CSHL Institutional Repository