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Research in the Pang Lab focuses on the function of Fanconi anemia (FA) proteins in hematopoiesis. The process of FA disease progression in the context of hematopoiesis is characterized by bone marrow failure, clonal proliferation of hematopoietic stem and progenitor (HSC/P) cells, and progression to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The only curable treatment for this devastating disease is stem cell therapy through bone marrow transplantation. We are studying how the FA proteins function in HSC maintenance and how loss of the FA protein function promotes malignant evolution of HSC/P cells. We are also interested in exploring a novel concept of manipulating the interaction between stem cell and bone marrow microenvironment or niche as a way to improve FA hematopoietic stem cell transplantation.
Amarachintha S, Sertorio M, Wilson A, Li X, Pang Q. Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling. Stem Cells. 2015 Jul 24. [Epub ahead of print].
Kato Y, Alavattam KG, Sin HS, Meetei AR, Pang Q, Andreassen PR, Namekawa SH. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015 Jun 29. [Epub ahead of print]
Li X, Zhang T, Wilson A, Amarachintha S, Sertorio M, Pang Q. Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse hematopoietic stem cells. Genom Data. 2015 Jun 1;4:148-149.
Zhang T, Wilson AF, Ali AM, Namekawa SH, Andreassen PR, Meetei AR, Pang Q. Loss of Faap20 causes hematopoietic stem and progenitor cell depletion in mice under genotoxic stress. Stem Cells. 2015 Jul;33(7):2320-30.
Li X, Li J, Wilson A, Sipple J, Schick J, Pang Q. Fancd2 is required for nuclear retention of FOXO3a in hematopoietic stem cell maintenance. J Biol Chem. 2015 Jan 30;290(5):2715-27.
Du W, Erden O, Wilson A, Sipple JM, Schick J, Mehta P, Myers KC, Steinbrecher KA, Davies SM, Pang Q. Deletion of Fanca or Fancd2 dysregulates Treg in mice. Blood. 2014 Mar 20;123(12):1938-47.
Li X, Li L, Li J, Sipple J, Schick J, Mehta PA, Davies SM, Dasgupta B, Waclaw RR, Pang Q. Concomitant inactivation of foxo3a and fancc or fancd2 reveals a two-tier protection from oxidative stress-induced hydrocephalus. Antioxid Redox Signal. 2014 Oct 20;21(12):1675-92.
Guo F, Li J, Zhang S, Du W, Sipple J, Phelan J, Grimes HL, Zheng Y, Pang Q. mTOR kinase inhibitor sensitizes T-cell lymphoblastic leukemia for chemotherapy-induced DNA damage via suppressing FANCD2 expression. Leukemia. 2014 Jan;28(1):203-6.
Li J, Pang Q. Oxidative stress-associated protein tyrosine kinases and phosphatases in Fanconi Anemia. Antioxid Redox Signal. 2014 May 10;20(14):2290-301.
Du W, Erden O, Pang Q. TNF-α signaling in Fanconi anemia. Blood Cells Mol Dis. 2014 Jan;52(1):2-11.
Du W, Amarachintha S, Sipple J, Schick J, Steinbrecher K, Pang Q. Inflammation-mediated Notch signaling skews Fanconi anemia hematopoietic stem cell differentiation. J Immunol. 2013 Sep 1;191(5):2806-17.
Guo F, Li J, Du W, Zhang S, O'Connor M, Thomas G, Kozma S, Zingarelli B, Pang Q, Zheng Y. mTOR regulates DNA damage response through NF-κB-mediated FANCD2 pathway in hematopoietic cells. Leukemia. 2013 Oct;27(10):2040-6.
Shen C, Oswald D, Phelps D, Cam H, Pelloski CE, Pang Q, Houghton PJ. Regulation of FANCD2 by the mTOR pathway contributes to the resistance of cancer cells to DNA double-strand breaks. Cancer Res. 2013 Jun 1;73(11):3393-401.
Guo F, Zhang S, Grogg M, Cancelas JA, Varney ME, Starczynowski DT, Du W, Yang JQ, Liu W, Zhu W, Thomas G, Kozma S, Pang Q, Zheng Y. Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis. Haematologica. 2013 Sep;98(9):1353-8.
Mehta PA, Svahn J, Davies SM, Pang Q, Harris R, Ghezzi P, Lanza T, Ferretti E, Barabino P, Mueller R, Dufour C. Etanercept treatment in Fanconi anaemia; combined US and Italian experience. Br J Haematol. 2012 Sep;158(6):809-11.
Li X, Sipple J, Pang Q, Du W. Salidroside stimulates DNA repair enzyme Parp-1 activity in HSC maintenance. Blood. 2012 May 3;119(18):4162-73.
Du W, Rani R, Sipple J, Schick J, Myers KC, Mehta P, Andreassen PA, Davies SM, Pang Q. The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters. Blood. 2012 May 3;119(18):4142-51.
Ali AM, Pradhan A, Singh TR, Du C, Li J, Wahengbam K, Grassman E, Auerbach AD, Pang Q, Meetei AR. FAAP20: a novel ubiquitin-binding FA nuclear core complex protein required for functional integrity of the FA-BRCA DNA repair pathway. Blood. 2012 Apr 5;119(14):3285-94.
Li J, Sipple J, Maynard S, Mehta PA, Rose SR, Davies SM, Pang Q. Fanconi Anemia Links Reactive Oxygen Species to Insulin Resistance and Obesity. Antioxid Redox Signal. 2012 Oct 15;17(8):1083-98.
Du W, Li X, Sipple J, Pang Q. Overexpression of IL-3R alpha on CD34+CD38- Stem Cells Defines Leukemia-Initiating Cells In FA AML. Blood. 2011;117(16):4243-52.
Du W, Li J, Sipple J, Chen J, Pang Q. A cytoplasmic FANCA-FANCC complex interacts and stabilizes the leukemic NPMc protein. J Biol Chem. 2010;285(48):37436-44.
Li J, Du W, Maynard S, Andreassen PR, and Pang, Q. Oxidative-stress specific interaction between FANCD2 and FOXO3a. Blood. 2010 Feb 25;115(8):1545-8.
Pang Q, Andreassen PR. Fanconi anemia proteins and endogenous stresses. Mutat Res. 2009;668:42-53.
Du W, Zhou Y, Pike S, and Pang, Q. NPM Phosphorylation Stimulates Cdk1, Overrides G2/M Checkpoint and Increases Leukemic Blasts in Mice. Carcinogenesis. 2009;31(2):302-10.
Rani R, Li J, Pang Q. Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice. Cancer Res. 2008;68(23):9693-702.
Zhou Y, Du W, Koretsky T, Bagby GC, Pang Q. TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice. Blood. 2008;112(6):2474-83.
Zhang X, Shang X, Guo F, Kirby M, Murphy K, Kelly P, Reeves L, Williams DA, Smith FO, Zheng Y, Pang Q. Defective homing is associated with altered Cdc42 activity in cells from Fanconi anemia group A patients. Blood. 2008;112(5):1683-6.
Du W, Adam Z, Rani R, Zhang X, Pang Q. Oxidative stress in Fanconi anemia hematopoiesis and disease progression. Antioxidants & Redox Signaling. 2008;10(11):1909-21.
Qishen Pang, PhDProfessorUC Department of Pediatrics
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