Fan Dong, M.D., Ph.D.
Office: WO 3257B
The long term goal of my research is to understand the molecular mechanisms involved in the regulation of blood cell development in the bone marrow and why disruption of these regulatory mechanisms may lead to blood malignancies, such as leukemia and lymphoma. Specifically, I am interested in two important regulators of blood cell development, i.e., granulocyte colony-stimulating factor (G-CSF) and growth factor independence 1 (Gfi1). G-CSF is a growth factor that plays a major role in the development of neutrophils, a type of white blood cells involved in host defense against bacterial infection. Gfi1 is a transcription factor that is critical for the development of white blood cells including myeloid and lymphoid cells. Aberrant activation of G-CSF signaling or Gfi1 has been implicated in leukemia and lymphoma, which contribute to approximately 8% of all cancer deaths in the United States.
CURRENT laboratory grants
Dong, Fan (PI)
ELANE and CSF3R mutations in severe congenital neutropenia
The goal of this project is to address the roles of ELANE and CSF3R mutations in severe congenital neutropenia. There is no overlap between this project and the current application.
Hu N, Qiu Y, Dong F. Role of Erk1/2 signaling in the regulation of neutrophil versus monocyte development in response to G-CSF and M-CSF. J Biol Chem. 290:2456, 2015.
Du P, Tang F, Qiu Y and Dong F. GFI1 is repressed by p53 and inhibits DNA damage-induced apoptosis. PLoS One. 8:e73542, 2013.
Liu Q and Dong F. Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation. Int J Hematol 95:640, 2012.
Liu Q, Basu S, Qiu Y, Tang F, and Dong F. A role of Miz-1 in Gfi-1-mediated transcriptional repression of CDKN1A. Oncogene 29:2843, 2010.
Basu S, Liu Q, Qiu Y, Dong F. Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A.106:1433, 2009.
Zhuang D, Qiu Y, Kogan SC, and Dong F. Increased CCAAT enhancer-binding protein epsilon (C/EBP) expression and premature apoptosis in myeloid cells expressing Gfi-1 N382S mutant associated with severe congenital neutropenia. J Biol Chem 281:10745, 2006.
Liu H, Qiu Y, Xiao L, and Dong F. Involvement of protein kinase Cepsilon in the negative regulation of Akt activation stimulated by granulocyte colony-stimulating factor. J Immunol. 176:2407, 2006.
Zhuang D, Qiu Y, Haque SJ and Dong F. Tyrosine 729 of the G-CSF receptor controls the duration of Stat5 activation: involvement of SOCS3 and SOCS1. J Leukoc Biol 78:1008, 2005.
Qiu Y, Zhuang D, Macrae A, Dong F. The G-CSF receptor carboxyl terminus, truncated in AML/SCN, is required for induction of a Stat5 protease activity. Leuk Res. 29:1153, 2005.
Shi T, Dong F, Liou LS, Duan ZH, Novick AA and DiDonato JA. Differential protein expression profiling and gene expression in renal cell carcinoma. Mol Carcinog. 40:47, 2004.
Dong F, Qiu Y, Yi T, Touw IP and Larner AC. The carboxy terminus of the granulocyte colony-stimulating factor receptor, truncated in patients with severe congenital neutropenia/acute myeloid leukemia, is required for SH2-containing phosphatase-1 suppression of Stat activation. J. Immunol. 167: 6447, 2001.
Dong F, Gutkind JS and Larner AC. Granulocyte colony-stimulating factor induces Erk5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. J Biol Chem. 276:10811, 2001.
Dong F, Larner AC. Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the Janus kinase(s). Blood 95:1656, 2000.
Grimley PM, Dong F, Rui H. 1999. Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation. Cytokine Growth Factor Rev 10:131-157.
Dong F, Liu, X, de Koning JP, Touw, IP, Hennighausen L, Larner A, Grimley P. Stimulation of Stat5 by Granulocyte Colony-Stimulating Factor (G-CSF) is Modulated by Two Distinct Cytoplasmic Regions of the G-CSF Receptor. J Immunol. 161:6503, 1998.
Rui H, Xu J, Mehta S, Fang H, Williams J, Dong F, Grimley PM. Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid. J. Biol. Chem. 273:28, 1998.
Grimley PM, Fang H, Rui H, Petricoin EF 3rd, Ray S, Dong F, Fields KH, Hu R, Zoon KC, Audet S, Beeler J. Prolonged STAT1 activation related to the growth arrest of malignant lymphoma cells by interferon-alpha. Blood l 91:3017, 1998
Stancato LF, Sakatsume M, David M, Dent P, Dong F, Petricoin EF, Krolewski JJ, Silvennoinen O, Saharinen P, Pierce J, Marshall CJ, Sturgill T, Finbloom D, and Larner AC. Beta interferon and oncostadin M activate Raf-1 and mitogen-activated protein kinase through a JAK-1-dependent pathway. Mol.Cel.Biol, 17:3833, 1997.
Dong F, Dale DC, Bonnila MA, Freedman M, Fasth A, Neijens HJ, Palmblad J, Briars GL, Calsson G, Veerman AJP, Welte K, Lowenberg B, Touw IP. Mutations in the Granulocyte-Colony Stimulating Factor Receptor Gene in Patients with Severe Congenital Neutropenia. Leukemia 11:120, 1997.
Touw IP, Dong F. 1996. Responses of leukemia cells to hematopoietic growth factors: Involvement of autocrine growth mechanisms, cytogenetic abnormalies, and defective maturation signaling. In: Blood Cell Biochemistgry, Vol. 7: Hematopoietic Cell Growth Factors (ed. A Whetton and J Gordon), Plenum, New York, London, Washington D.C., Boston, Moscow, pp303.
Touw IP and Dong F. 1996. Severe Congenital Neutropenia Terminating in Acute Leukemia: Disease Progression Associated with Mutations in the Granulocyte-Colony Stimulating Factor Receptor Gene. Leuk. Res. 20:629-631.
Touw IP and Dong F. 1996. Hematopoietic growth factors in leukemia. Path. Res. Pract. 192:734-742.
Barge RMY, de Koning JP, Pouwels K, Dong F, Lowenberg B, Touw IP. Tryptophan 650 of Human Granulocyte Colony-Stimulating Factor (G-CSF) Receptor, Implicated in the Activation of JAK2, Is also Required for G-CSF-mediated Activation of Signaling Complexes of the p21ras Route. Blood 87:2148, 1996.
de Koning JP, Dong F (Co-first author), Smith L, Schelen AM, Barge RM.Y, van der Plas DC, Hoefsloot LH, Lowenberg B, Touw IP. The Membrane-Distal Cytoplasmic Region of Human Granulocyte Colony-Stimulating Factor Receptor Is Required for STAT3 but not STAT1 Homodimer Formation. Blood 87:1335, 1996.
de Koning JP, Schelen AM, Dong F, van Buitenen C, Burgering BMT, Bos JL, Lowenberg B, Touw IP. Specific Involvement of Tyrosine 764 of Human Granulocyte Colony-Stimulating Factor Receptor in Signal Transduction Mediated by p145/GRB2 or p90/GRB2 Complexes". Blood 87:132, 1996.
Dong F, Pouwls K, Hoefsloot LH, Rozemuller H, Lowenberg B, Touw IP. The C-terminal Cytoplasmic Region of the Granulocyte Colony-Stimulating Factor Receptor Mediates Apoptosis in Maturation-Incompetent Murine Myeloid Cells". Exp. Hematol 24:214, 1996.
Budel LM, Dong F, Lowenberg B, Touw IP. 1995. Hematopoietic Growth Factor Receptor: Structure Variations and Alternatives of Receptor Complex Formation in Normal Hematopoiesis and in Hematopoietic Disorders. Leukemia 9:553-561.
Dong F, Brynes RK, Tidow N, Welte K, Lowenberg B, Touw IP. Mutations in the Gene for the Granulocyte Colony-Stimulating Factor Receptor in Patients with Acute Myeloid Leukemia Preceded by Severe Congenital Neutropenia". N.Engl J Med 333:487, 1995.
Dong F, van Paassen M, van Buitenen C, Hoofsloot LH, Lowenberg B, Touw IP. A Point mutation in the Granulocyte Colony-Stimulating Factor Receptor (G-CSF-R) Gene in a Case of Acute Myeloid Leukemia Results in the Overexpression of a Novel G-CSF-R Isoform. Blood 85:902, 1995.
Dong F, Hoefsloot LH, Schelen AM, Broeders LCAM, Meijer Y, Veerman AJP, Touw IP, Lowenberg B. Identification of a Nonsense Mutation in the Granulocyte-Colony Stimulating Factor Receptor in Severe Congenital Neutropenia. Proc.Natl Acad Sci. USA. 91:4480, 1994.
Dong F, van Buitenen C, Pouwles K, Hoefsloot LH, Lowenberg B, Touw IP. Distinct Cytoplasmic Regions of the Human Granulocyte Colony-Stimulating Factor Receptor Involved in Induction of Proliferation and Maturation. Mol.Cel Biol. 13:7774-7781, 1993.