CURRENT RESEARCH INTERESTS
structure, genome architecture, epigenetics, hematopoiesis, stem cell biology, and
The focus of our research is on understanding the mechanisms underlying development and tumorigenesis through deciphering the structure-function relationship of mammalian genomes. We have developed a series of high throughput methods for mapping three-dimensional (3D) genome architecture globally or locally. Recently, in collaboration with the investigators in the University of Washington Center for Nuclear Organization and Function (UW-CNOF), we developed a single-cell Hi-C method for characterize the 3D genome architecture in thousands of single cells in a massively parallel fashion.
We have used these tools to dissect the dynamics of 3D genome organization in the context of a variety of biological systems. One of our current focuses is to characterize the nuclear morphology-associated 3D genome rearrangement and epigenetic programming during blood cell maturation and the pathogenesis of hematologic disorders.
Ramani, V., Deng, X., Gunderson, K. L., Steemers, F. J., Disteche, C. M., Noble, W. S., Duan, Z.#, and Shendure, J# (#, Co-Correspondence). (2016) Massively multiplex single-cell Hi-C. bioRxiv, 10.1101/065052, Submitted
Ramani V, C. D., Hause RJ, Ma W, Deng X, Blau CA, Disteche CM, Noble WS, Shendure J#, and Duan Z# (#, Co-Correspondence). (2016) Mapping three-dimensional genome architecture through in situ DNase Hi-C. Nature Protocols. Accepted.
Ramani, V., Shendure, J., and Duan, Z. (2016) Understanding Spatial Genome Organization: Methods and Insights. Genomics, proteomics & bioinformatics 14, 7-20.
Deng, X., Ma, W., Ramani, V., Hill, A., Yang, F., Ay, F., Berletch, J. B., Blau, C. A., Shendure, J., Duan, Z.#, Noble, W. S.#, and Disteche, C. M# (#, Co-Correspondence). (2015) Bipartite structure of the inactive mouse X chromosome. Genome biology 16, 152
Ma, W., Ay, F., Lee, C., Gulsoy, G., Deng, X., Cook, S., Hesson, J., Cavanaugh, C., Ware, C. B., Krumm, A., Shendure, J., Blau, C. A., Disteche, C. M., Noble, W. S.#, and Duan, Z# (#, Co-Correspondence). (2015) Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes. Nature methods 12, 71-78
Duan, Z.#, and Blau, C. A# (#, Co-Correspondence). (2012) The genome in space and time: does form always follow function? How does the spatial and temporal organization of a eukaryotic genome reflect and influence its functions? Bioessays 34, 800-810
Duan, Z.#, Andronescu, M., Schutz, K., Lee, C., Shendure, J., Fields, S., Noble, W. S.#, and Anthony Blau, C# (#, Co-Correspondence). (2012) A genome-wide 3C-method for characterizing the three-dimensional architectures of genomes. Methods 58, 277-288
Duan, Z., Andronescu, M., Schutz, K., McIlwain, S., Kim, Y. J., Lee, C., Shendure, J., Fields, S., Blau, C. A., and Noble, W. S. (2010) A three-dimensional model of the yeast genome. Nature 465, 363-367
Ware, C. B., Wang, L., Mecham, B. H., Shen, L., Nelson, A. M., Bar, M., Lamba, D. A., Dauphin, D. S., Buckingham, B., Askari, B., Lim, R., Tewari, M., Gartler, S. M., Issa, J. P., Pavlidis, P., Duan, Z., and Blau, C. A. (2009) Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell stem cell 4, 359-369
Duan, Z., Person, R. E., Lee, H. H., Huang, S., Donadieu, J., Badolato, R., Grimes, H. L., Papayannopoulou, T., and Horwitz, M. S. (2007) Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5. Molecular and cellular biology 27, 6889-6902
Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H. L., and Horwitz, M. (2005) Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Molecular and cellular biology 25, 10338-10351
Duan, Z., and Horwitz, M. (2005) Gfi-1 takes center stage in hematopoietic stem cells. Trends in molecular medicine 11, 49-52
Duan, Z., Li, F. Q., Wechsler, J., Meade-White, K., Williams, K., Benson, K. F., and Horwitz, M. (2004) A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Molecular and cellular biology 24, 58-70
Person, R. E., Li, F. Q., Duan, Z., Benson, K. F., Wechsler, J., Papadaki, H. A., Eliopoulos, G., Kaufman, C., Bertolone, S. J., Nakamoto, B., Papayannopoulou, T., Grimes, H. L., and Horwitz, M. (2003) Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nature genetics 34, 308-312
Horwitz, M., Li, F. Q., Albani, D., Duan, Z., Person, R. E., Meade-White, K., and Benson, K. F. (2003) Leukemia in severe congenital neutropenia: defective proteolysis suggests new pathways to malignancy and opportunities for therapy. Cancer investigation 21, 579-587