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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.
Du W, Amarachintha S., Sipple J, Schick J., Steinbrecher K. and Pang Q. Inflammation-mediated Notch signaling skews Fanconi anemia hematopoietic stem cell differentiation. J. Immunol., 2013 Sep 1;191(5):2806-17.Aug 7. [Epub ahead of print].
Guo F, Li J, Zhang S, Du W, Sipple J, Phelan J, Grimes HL, Zheng Y, and Pang Q. mTOR kinase inhibitor sensitizes T-cell lymphoblastic leukemia for chemotherapy-induced DNA damage via suppressing FANCD2 expression. Leukemia. 2013 Jul 15. [Epub ahead of print].
Du W, Erden O, Pang Q. TNF-α signaling in Fanconi anemia. Blood Cells Mol Dis. 2013 Jul 24. [Epub ahead of print]
Guo F, Li J, Du W, Zhang S, O'Connor M, Thomas G, Kozma S, Zingarelli B, Pang Q, Zheng Y. (2013) mTOR regulates DNA damage response through NF-κB-mediated FANCD2 pathway in hematopoietic cells.Leukemia. 2013 Mar 29. [Epub ahead of print]. PMID:23538752
Shen C, Oswald D, Phelps D, Cam H, Pelloski CE, Pang Q, Houghton PJ. (2013) Regulation of FANCD2 by the mTOR Pathway Contributes to the Resistance of Cancer Cells to DNA Double-Strand Breaks.Cancer Res. 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.May 28. [Epub ahead of print]
Li X, Sipple J, Pang Q, and Du W. Salidroside stimulates DNA repair enzyme Parp-1 activity in HSC maintenance. Blood. 119, 4162-4173. 2012.
Du W, Rani R, Sipple J, Schick J, Myers KC, Mehta P, Andreassen PA, Davies SM, and Pang Q. The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters. Blood. 119(18):4142-51. 2012.
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. 119(14):3285-94. 2012.
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. 17(8):1083-98. 2012.
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. 158(6):809-11. 2012.
Du, W. Li, J. Sipple, J. Chen, J. and Pang,Q. A cytoplasmic FANCA-FANCC complex interacts and stabilizes the leukemic NPMc protein. J Biol Chem. 285(48):37436-44. 2010.
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. 2010.
Pang Q, Andreassen PR. Fanconi anemia proteins and endogenous stresses. Mutat. Res., 668:42-53. 2009.
Du W, Zhou Y, Pike S, and Pang, Q. NPM Phosphorylation Stimulates Cdk1, Overrides G2/M Checkpoint and Increases Leukemic Blasts in Mice. Carcinogenesis 31(2):302-10. 2009.
Rani R, Li J, Pang Q. Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice. Cancer Res. 68(23):9693-702. 2008.
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, 112(6):2474-83. 2008.
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, 112(5):1683-6. 2008.
Du W, Adam Z, Rani R, Zhang X, Pang Q. Oxidative stress in Fanconi anemia hematopoiesis and disease progression. Antioxidants & Redox Signaling, 10(11):1909-21. 2008.
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