Education and Training:

B.S., Hua Zhong University of Science and Technology, Wuhan, China (1987-92)

Ph.D., Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai, China (1992-97) 

Post-doctoral Senior Fellow in Dr. G. Stamatoyannopoulo's laboratory, Division of Medical Genetics, University of Washington (1997-2000) 

Post-doctoral Senior Fellow in Dr. Marshall Horwitz' laboratory, Division of Medical Genetics, University of Washington (2000-2003)

CURRENT RESEARCH INTERESTS

Chromatin structure, genome architecture, epigenetics, stem cell biology, and cancer biology

RESEARCH DESCRIPTION

The focus of our research is on the relationship between the form and function of human genomes during development and tumorigenesis. One of the striking features of the eukaryotic nucleus is that chromosomes adopt preferred conformations that vary across different tissues and developmental stages.

More than 10 years after its initial description, only a small fraction of the human genome is functionally annotated. For the vast majority of the human genome, the specific function of the most of the DNA is still unknown. During the past few years, systematic approaches for the global identification of various functional elements in the human genome have been developed. However, determining the in vivo activities of these elements remains a major challenge. Since the in vivo function of these elements is not confined to linearly adjacent sequences, characterizing both the local and global chromosome structure will be crucial to understanding the underlying regulatory mechanisms.

Our current goal is to develop routinely affordable high throughput tools for globally characterizing chromatin interactions in mammalian cells and to adapt these tools for characterizing structural relationships among functional elements in human pluripotent stem cells. Through integrative genomic analysis, we aim to model the cis-regulatory networks in these cells and to reveal the roles of such networks in self-renewal and differentiation.  

SELECTED PUBLICATIONS

Duan Z*, Andronescu M* (*Contributed equally), Schutz K, Mcllwain S, Kim JY, Lee C, Shendure J, Fields S, Blau CA, and Noble WS.  A three-dimensional model of the yeast genome. Nature, 2010, 465:363-367. doi:10.1038/nature08973. 

Salipante SJ, Rojas ME, Korkmaz B, Duan Z, Wechsler J, Benson KF, Person RE, Grimes HL, and Horwitz MS.  Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.  Mol Cell Biol, 2009, 29: 4394-4405

Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, and Blau CA.  Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells.  Cell Stem Cell, 2009, 4:359-369

Duan Z, Person RE, Lee HH, Huang S, Badolato R, Donadieu J, and Horwitz M.  Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5.  Mol Cell Biol, 2007, 27: 6889-6902

Horwitz M, Duan Z, Korkmaz K, Lee HH, Mealiffe ME, and Salipante SJ.  Neutrophil elastase in cyclic and severe congenital neutropenia.  Blood, 2007, 109: 1817-1824

Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, and Horwitz M.  Gfi1 coordinates epigenetic repression of p21cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase HDAC1.  Mol Cell Biol, 2005, 25: 10338-10351

Duan Z and Horwitz M.  Gfi-1 takes center stage in hematopoietic stem cells.  Trends Mol Med, 2005, 11: 49-52

Doan LL, Porter SD, Duan Z, Jay CM, Flubacher MM, Tsichlis PN, Horwitz M, Gilks CB, and Grimes HL.  Targeted transcriptional repression of Gfi1 by Gfi1 and Gfi1B in lymphoid cells.  Nucleic Acids Res, 2004, 32: 2508-2519

Horwitz M, Benson KF, Duan Z, Li FQ and Person RE.  Hereditary neutropenia: dogs make sense of human mutations.  Trends Mol Med, 2004, 10: 263-270

Duan Z, Li FQ, Meade-White K, Williams K, Benson KF and Horwitz M.  A novel Notch protein targeted by neutrophil elastase and implicated in hereditary neutropenia.  Mol Cell Biol, 2004, 24: 58-70

Duan Z and Horwitz M.  Gfi-1 oncoproteins in hematopoiesis.  Hematology, 2003, 8: 339-344

Benson KF, Li FQ, Person RE, Albani D, Duan Z, Wechesler J, Meade-White K, Williams K, Acland GA, Niemeyer G, Lothrop CD and Horwitz M.  Canine cyclic hematopoiesis: dog and human neutropenia mutations disrupt intracellular transport of neutrophil elastase.  Nature  Genet, 2003, 35: 90-96

Person RE*, Li FQ*,  Duan Z* (*Contributed equally),  Benson KF, Wechesler J,  Papadaki HA, Eliopoulos G, Kaufman C, Bertolone SJ, Nakamoto B, Papayannopoulu T, Grimes HL and Horwitz M.  Mutations in proto-oncogene Gfi1 cause human neutropenia and target ELA2.  Nature Genet, 2003, 34: 308-312

Duan Z and Horwitz M.  Targets of the transcriptional repressor oncoprotein Gfi-1.  Proc Natl Acad Sci, 2003, 100: 5932-5937

Horwitz M, Benson KF, Duan Z, Person RE, Wechesler J, Williams K, Albani D and Li FQ.  The role of neutrophil elastase in bone marrow failure syndromes: molecular genetics revival of the “chalone” hypothesis.  Curr Opin Hematol, 2003, 10: 49-54

Duan Z*, Fang XD* (*Contributed equally), Hu Z, Rohde A, Han H, Stamatoyannopoulos G and Li Q.  Developmental specificity of recruitment of TBP to the TATA box.  Proc Natl Acad Sci, 2002, 99: 5509-5514

Horwitz M, Li FQ, Albani D, Duan Z, Person RE, Meade-White K and Benson KF.  Leukemia in severe congenital neutropenia: defective proteolysis suggests new pathways to malignancy and opportunities for therapy.  Cancer Invest, 2003, 21: 579-597

Duan Z, Stamatoyannopoulos G and Li Q.  Role of NF-Y in in vivo regulation of the g-Globin Gene.  Mol Cell Biol, 2001, 21: 3083-3095

Li Q, Duan Z and Stamatoyannopoulos G. Analysis of the mechanism of action of non-deletion hereditary persistence of fetal hemoglobin mutants in transgenic mice. EMBO J, 2001, 20: 157-164

Yang JB, Duan Z, Yao W, Lee O, Yang L, Yang XY, Sun X, Chang CCY, Chang TY and Li BL. Synergistic transcriptional activation of human acyl-coenzyme A:cholesterol acyltransferase-1 gene by interferon- and all-trans-retinoic acid in THP-1 cells. J Biol Chem, 2001, 276: 20989-20998

Yang Y, Duan Z, Skapidi E, Li Q, Papayannoupoulou T and Stamatoyannopoulos G. Cloning and characterization of a potential transcriptional activator of human -globin genes. Blood Cells Mol Dis, 2001, 27: 1-15

Li Q, Zhang M, Duan Z and Stamatoyannopoulos G. Structural analysis and mapping of DNase I hypersensitivity of HS5 of the beta-globin locus control region. Genomics, 1999, 61: 183-93

Li BL, Li XL, Duan Z, Lee O, Lin S, Ma ZM, Chang CCY, Yang XY, Park JP, Mohandas TK, Noll W, Chan L and Chang TY.  Human acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) gene organization and evidence that the 4.3 kb mRNA is produced from two different chromosomes.  J Biol Chem, 1999, 274: 11060-11071

Xu ZP, Chen H, Duan Z and Li BL. Studies on structure and function of the myristoyltransferase inhibitor peptide displayed on phage surface.  Acta Biochim Biophys Sin, 1998, 30: 231-235 (in Chinese)

Xu ZP, Duan Z, Chen CZ and Li BL. C-terminal His-tag fusion expression and purification of truncated cAMP-dependent protein kinase.  Acta Biochim Biophys Sin, 1998,  30: 174-178 (in Chinese)

Xu ZP, Duan Z, Chen H, Chen CZ and Li BL. Selection of myristoyltransferase inhibitor phages from phage display random peptide library.  Acta Biochim Biophys Sin, 1998, 30: 154-158 (in Chinese)

Xu ZP, Duan Z, Chen CZ, Yang XY and Li BL. His6 fusion expression of myristoyl-CoA: protein N-myristoyltransferase in E. coli and its purification.  Acta Biochim Biophys Sin, 1997, 29: 383-388 (in Chinese)

Duan Z, Chen CZ, Yang XY, Li BL and Wang DB (Wang TP).  Coexpression system for protein N-myristoylation in E. coli.  Chin J Biotech, 1996, 12(S): 10-16 (in Chinese)

Chen CZ, Duan Z, Yang XY, Xia QC, Li BL and Wang YL. A T7 promoter-based versatile expression vector system for E. coli.  Acta Biochim Biophys Sin, 1996, 28: 531-539 (in Chinese); Chin J Biochem Biophys, 1997, 29: 249-257 (in English)

Duan Z, Chen CZ and Li BL. Cloning and expression of the yeast Saccaromyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase gene in E. coli.  Acta Biochim Biophys Sin, 1996, 28: 115-123 (in Chinese); Chin J Biochem Biophys, 1997, 29: 33-41 (in English)

Li BL and Duan Z. Molecular mechanism in the regulation of cholesterol metabolic homeostasis.  Prog Biotech, 1996, 16: 27-33 (Review in Chinese)