2012-present, Associate Professor, Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, California
2005-present, Full Member, Comprehensive Cancer Center of City of Hope, Duarte, California
2005-present, Faculty, City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, California
2005-2011, Assistant Professor, Division of Biology, Beckman Research Institute of City of Hope, Duarte, California

Research

Our laboratory focuses on epigenetics, aging and cancer. Epigenetic modifications play important roles in many normal biological processes, such as development, stem cell differentiation and aging, as well as in disease settings such as cancer. Stem cells are regulated by many epigenetic factors. Among them, sirtuin 1 (SIRT1) is a mammalian stress-response gene encoding an NAD-dependent protein lysine deacetylase that plays diverse roles in metabolism, aging and cancer. Our group has made a seminal contribution to the field by showing that SIRT1 is activated by oncogenic transformation of hematopoietic stem cells and promotes leukemogenesis and drug resistance of leukemic stem cells to therapeutic agents. Our studies suggest that SIRT1 is a promising therapeutic target for treatment of leukemia and perhaps other malignancies. We will further decipher the roles of SIRT1 and other epigenetic regulators in hematopoietic stem cells during aging and leukemogenesis and develop novel treatment strategies for cancer. We will investigate NAD metabolism affecting sirtuin functions in carcinogenesis as well as cancer therapeutic response

Lab Members

Alessia Bortoluzzi, Ph.D.
Postdoctoral Fellow
626-256-HOPE, ext. 82823
abortoluzzi@coh.org

Publications

Wang Z, Zhang C, Warden C, Wang J, Wang C, Yuan YC, Wu X, Guo C, Vonderfecht SL, Ermel R, Wang X, Brown C, Forman S, You JM & Chen WY. (2022) Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia. Communication Biology 5: 396, 1-15. PubMed PMID: 35484199; PubMed Central PMCID: PMC9051098.
Hao T, Zhang C, Wang Z, Buck A, Vonderfecht S, Ermel R, Kim Y & Chen WY. (2021) An aging mouse model of human chronic myeloid leukemia. Oncogene 40: 3152-3163. PubMed PMID: 33824471; PubMed Central PMCID: PMC8087641.
Kim N, Kim MY, Cho YU, Chen WY, Lee KH & Kim HS. (2020) PVR and ICAM-1 on Blast Crisis CML Stem and Progenitor Cells with TKI Resistance Confer Susceptibility to NK Cells. Cancers 12(7): 1923, 1-11. PubMed PMID: 32708713; PubMed Central PMCID: PMC7409178.
Hao T, Li-Talley M, Buck A & Chen WY. (2019) An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States. Scientific Reports 9: 12070, 1-13. PubMed PMID: 31427635; PubMed Central PMCID: PMC6700310.
Tharkar-Promod S,Johnson DP, Bennett SE, Dennis EM, Banowsky BG, Jones SS, Shearstone JR, Quayle SN, Min C, Jarpe M, Mosbruger T, Pomicter AD, Miles RR, Chen WY, Bhalla KN, Zweidler-McKay PA, Shrieve DC, Deininger MV, Chandrasekharan MB, & Bhaskara S. (2018) HDAC1,2 inhibition and doxorubicin impair Mre11-dependent DNA repair and DISC to override BCR-ABL1-driven DSB repair in Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia. Leukemia. 32: 49–60. doi.org/10.1038/leu.2017.174
Roth M, Wang Z, Chen WY. (2016) SIRT1 & LSD1 competitively regulate KU70 functions in DNA repair and mutation acquisition in cancer cells. Oncotarget 7: 50195-50214. doi.org/10.18632/oncotarget.10328
Wang Z, Chen WY. (2016) A convenient cell culture model for CML acquired resistance through BCR-ABL mutations. Methods in Molecular Biology. 1465:149-157. doi.org/10.1007/978-1-4939-4011-0_13
Reverchon M, Ramé C, Bunel A, Chen WY, Froment P, & Dupont J. (2016) VISFATIN (NAMPT) Improves In Vitro IGF1-Induced Steroidogenesis and IGF1 Receptor Signaling Through SIRT1 in Bovine Granulosa Cells. Biol Reprod. 94(3):54, 1-13. doi.org/10.1095/biolreprod.115.134650
Wang Z, Chen, CC, Chen WY. (2015) CD150- side population defines leukemia stem cells in a mouse model of chronic myelogenous leukemia in BABL/c mice and is depleted by genetic loss of SIRT1. Stem Cells. 33:3437-3451. PubMed PMID: 26466808; PubMed Central PMCID: PMC4713280
Cloix L, Reverchon M, Cornuau M, Froment P, Ramé C, Costa C, Froment G, Lecomte P, Chen WY, Guerif F, Royère D, & Dupont J. (2014) Expression and regulation of INTELECTIN1 (ITLN1) in human granulosa-lutein cells: Role in IGF1-induced steroidogenesis through NAMPT. Biol Reprod. 91(2) 50, 1-13. PubMed PMID: 24943040.
Li L, Osdal T, Ho Y, Chun S, McDonald T, Agarwal P, Lin A, Chu S, Qi J, Li L, Hsieh YT, Dos Santos C, Yuan H, Ha TQ, Popa M, Hovland R, Bruserud O, Gjertsen BT, Kuo YH, Chen WY, Lain S, McCormack E, & Bhatia R. (2014) SIRT1 activation by a c-MYC Oncogenic Network Promotes the Maintenance and Drug Resistance of Human FLT3-ITD Acute Myeloid Leukemia Stem Cells. Cell Stem Cell. 15: 431-46. PubMed PMID: 25280219; PubMed Central PMCID: PMC435398.
Wang, Z., Liu, Z., Wu X., Chu, S., Wang, J.H., Yuan, H., Roth, M., Yuan, Y.C., Bhatia, R. & Chen, W.Y. (2014) ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance. PloS Genet. 10: e1004414.PubMed PMID: 24967705; PubMed Central PMCID: PMC4072521.
Roth, M. & Chen W.Y. (2014) Sorting out functions of sirtuins in cancer. Oncogene. 33(13):1609-20. PubMed PMID: 23604120; PubMed Central PMCID: PMC4295628.
Roth M, Wang Z, Chen WY. (2013) Sirtuins in hematological aging and malignancy. Critical Reviews in Oncogenesis. 18(6):485-501. PubMed PMID: 24579733; PubMed Central PMCID: PMC3951433.
Yuan H, Su L, Chen WY. (2013) The emerging and diverse roles of sirtuins in cancer: A clinical perspective. Oncotarget & Therapy 6:1399-1416. PubMed PMID: 24133372; PubMed Central PMCID: PMC3797239.
Wang Z, Chen WY. (2013) Emerging roles of SIRT1 in cancer drug resistance. Genes & Cancer. 4: 82-90. PubMed PMID: 24019998; PubMed Central PMCID: PMC3764475.
Chen WY, Bhatia R. (2013) Roles of SIRT1 in leukemogenesis. Curr Opin Hematol 20: 308-313. PubMed PMID: 23519155; PubMed Central PMCID: PMC3808881.
Wang Z, Yuan H, Roth M, Stark J, Bhatia R, Chen WY. (2013) SIRT1 deacetylase promotes acquisition of genetic mutations for drug resistance in CML cells. Oncogene 32: 589-598. PubMed PMID: 22410779; PubMed Central PMCID: PMC3376246.
Chen WY. (2012) Accelerating cancer evolution: a dark side of SIRT1 in genome maintenance. Oncotarget 3: 363-364. PubMed PMID: 22622047; PubMed Central PMCID: PMC3380571.
Chakraborty S, Stark JM, Sun CL, Modi H, Chen WY. O’Connor T, Forman SJ, Bhatia S, Bhatia R. (2012) Chronic Myelogenous Leukemia Stem and Progenitor Cells Demonstrate Chromosomal Instability Related to Repeated Breakage-Fusion-Bridge Cycles Mediated by Non-Homologous End Joining. Blood 119: 6187-6197. PubMed PMID:22493298; PubMed Central PMCID: PMC3383199.
Nam S, Scuto A, Yang F, Chen WY., Park S, Yoo HS, Konig H, Bhatia R, Cheng X, Merz KH, Eisenbrand G, Jove R. (2012) Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of STAT5 signaling. Molecular Oncology 6: 276-283. PubMed PMID: 22387217; PubMed Central PMCID: PMC3361532.
Yuan H, Wang Z, Zhang H, Bhatia R, Chen WY. (2012) Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model. Carcinogenesis 33: 285-293. PubMed PMID: 22116466; PubMed Central PMCID: PMC3271265.
Li L, Wang L, Li L, McDonald T, Ho Y, Holyoake T, Chen WY.^#, Bhatia R. ^# (2012) Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with Imatinib. Cancer Cell 21: 266-281. PubMed PMID: 22340598; PubMed Central PMCID: PMC3285436. ^#Co-corresponding authors.
Yuan H, Wang Z, Li L, Zhang H, Modi H, Horne D, Stark J, Bhatia R^#, Chen WY.^# (2012) Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood 119: 1904-1914. PubMed PMID: 22207735; PubMed Central PMCID: PMC3293644 ^#Co-corresponding authors.
Wang B, Hasan KM, Alvarado E, Yuan H, Wu H, Chen WY. (2011) NAMPT over-expression in prostate cancer and its contribution to tumor cell survival and stress response. Oncogene 30: 907-921. PubMed PMID: 20956937.
Chen WY, Yuan H, Wang Z. (2011) De novo acquisition of BCR-ABL mutations for CML acquired resistance. In Myeloid Leukemia: Basic Mechanisms of Leukemogenesis. Steffen Koschmieder and Utz Krug (eds). pp 69-84. doi:10.5772/28990.
Yuan H, Wang Z, Gao C, Chen W, Huang Q, Yee JK, Bhatia R, Chen WY. (2010) BCR-ABL gene expression is required for its mutations in a novel KCL-22 cell culture model for acquired resistance of chronic myelogenous leukemia. J Biol Chem 285:5085-5096. PubMed PMID: 20007699; PMCID: PMC2836111.
Chen WY, Wang DH, Chiu RW, Lou JY, Gu W, Baylin SB. (2005) Tumor suppressor HIC1 directly regulates SIRT1 deacetylase to modulate p53-dependent apoptotic DNA damage responses. Cell, 123:437-448. PubMed PMID: 16269335.
Chen WY, Cooper TK, Zahnow CA, Overholtzer M, Zhao Z, Ladanyi M, Karp E, Gokgoz N, Wunder JS, Andrulis IL, Levine AJ, Mankowski JL, Baylin, SB. (2004) Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis. Cancer Cell, 6:387-398. PubMed PMID: 15488761.
Chen WY, Zeng X, Carter MG, Morrell CN, Chiu Yen RW, Esteller M, Watkins DN, Herman JG, Mankowski JL, Baylin SB. (2003) Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors. Nat Genet, 33, 197-202. PubMed PMID: 12539045.
Chen WY, Wu X, Levasseur DN, Liu H, Lai L, Kappes JC, Townes TM. (2000) Lentiviral vector transduction of hematopoietic stem cells that mediate long-term reconstitution of lethally irradiated mice. Stem Cells, 18, 352-359. PubMed PMID: 11007919.
Chen WY, Townes TM. (2000) Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci U S A,97, 377-382. PubMed PMID: 10618426; PubMed Central PMCID: PMC26671.
Chen WY, Bailey EC, McCune SL, Dong JY, Townes TM. (1997) Reactivation of silenced, virally transduced genes by inhibitors of histone deacetylase. Proc Natl Acad Sci U S A, 94, 5798-5803. PubMed PMID: 9159154; PubMed Central PMCID: PMC20860.

For my complete list of published works, see my bibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/wenyong.chen.1/bibliography/41463954/public/?sort=date&direction=ascending.