Co-Leader, Pilot and Collaborative Translational Clinical Studies Program
Professor, Microbiology, Immunology & Molecular Genetics
Member, CTSI, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC)
The overall research interests of this laboratory are to understand, at the molecular and cellular levels, how the human retroviruses, human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV), cause AIDS and cancer, respectively. We are also developing gene therapy reagents and modeling these reagents utilizing the SCID-hu mouse, which allows stem cell reconstitution and thymic T-cell development. Some of the specific projects ongoing in this laboratory are: 1. The mechanism by which HIV-1 causes CD4+ T-cell death is unknown. We have found that HIV-1 causes perturbation of the cell cycle, leading to arrest of the cells at a particular point in the cycle. Furthermore, this ability of HIV-1 to arrest T-cells can be abrogated by specific mutations within one of the non-structural genes of the virus. We are investigating the role of this gene, termed vpr, and the specific cell cycle kinases, cyclins and cell cycle inhibitors that may be involved in this process. 2. Immune reconstitution is theoretically a viable approach to AIDS therapy. However, the new T-cells need to be protected from the effects of residual HIV-1. We are modeling gene therapy utilizing the SCID-hu mouse for introduction of “protected” CD34+ stem cells, reconstitution of the SCID-hu animal and finally, challenge with HIV-1. This is the only model for human stem cell gene therapy, and allows for more rapid experimental design of vectors, reagents, etc.
Dr. Irvin S. Y. Chen, Director of the UCLA AIDS Institute, is Professor of Microbiology, Immunology, Molecular Genetics and Professor of Medicine at the David Geffen School of Medicine at UCLA, and is an internationally recognized retrovirologist and molecular biologist. Dr. Chens focus is on human retroviruses that are implicated in cancer and AIDS. This form of virus reproduces by creating DNA from RNA and adding its genetic code to the chromosomes of the cells it has infected. Along with his exploration of the disease-causing process of the AIDS virusHIV (human immunodeficiency virus), Dr. Chen also was instrumental in identifying HTLV II, a human T-cell leukemia virus. Dr. Chen was the co-inventor of a diagnostic test for this virus currently used in blood banks throughout the world.
Presson Angela P, Kim Namshin, Xiaofei Yan, Chen Irvin Sy, Kim Sanggu Methodology and software to detect viral integration site hot-spots. BMC bioinformatics
. 2011; 12: 367.
Zhang Kai-xin, Kim Connie, Chow Elaine, Chen Irvin S Y, Jia William, Rennie Paul S Targeting trastuzumab-resistant breast cancer cells with a lentivirus engineered to bind antibodies that recognize HER-2. Breast cancer research and treatment
. 2011; 125(1): 89-97.
Morizono Kouki, Xie Yiming, Olafsen Tove, Lee Benhur, Dasgupta Asim, Wu Anna M, Chen Irvin S Y The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell host & microbe
. 2011; 9(4): 286-98.
Shimizu Saki, Hong Patrick, Arumugam Balamurugan, Pokomo Lauren, Boyer Joshua, Koizumi Naoya, Kittipongdaja Panyamol, Chen Angela, Bristol Greg, Galic Zoran, Zack Jerome A, Yang Otto, Chen Irvin S Y, Lee Benhur, An Dong Sung A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model. Blood
. 2010; 115(8): 1534-44.
Kamata Masakazu, Liu Shirley, Liang Min, Nagaoka Yoshiko, Chen Irvin S Y Generation of human induced pluripotent stem cells bearing an anti-HIV transgene by a lentiviral vector carrying an internal murine leukemia virus promoter. Human gene therapy
. 2010; 21(11): 1555-67.
Kim Sanggu, Kim Namshin, Presson Angela P, An Dong Sung, Mao Si Hua, Bonifacino Aylin C, Donahue Robert E, Chow Samson A, Chen Irvin S Y High-throughput, sensitive quantification of repopulating hematopoietic stem cell clones. Journal of virology
. 2010; 84(22): 11771-80.
Liang Min, Kamata Masakazu, Chen Kevin N, Pariente Nonia, An Dong Sung, Chen Irvin S Y Inhibition of HIV-1 infection by a unique short hairpin RNA to chemokine receptor 5 delivered into macrophages through hematopoietic progenitor cell transduction. The journal of gene medicine
. 2010; 12(3): 255-65.
Kamata Masakazu, Liang Min, Liu Shirley, Nagaoka Yoshiko, Chen Irvin S Y Live cell monitoring of hiPSC generation and differentiation using differential expression of endogenous microRNAs. PloS one
. 2010; 5(7): e11834.
Morizono Kouki, Ku Amy, Xie Yiming, Harui Airi, Kung Sam K P, Roth Michael D, Lee Benhur, Chen Irvin S Y Redirecting lentiviral vectors pseudotyped with Sindbis virus-derived envelope proteins to DC-SIGN by modification of N-linked glycans of envelope proteins. Journal of virology
. 2010; 84(14): 6923-34.
Morizono Kouki, Xie Yiming, Helguera Gustavo, Daniels Tracy R, Lane Timothy F, Penichet Manuel L, Chen Irvin S Y A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide. The journal of gene medicine
. 2009; 11(8): 655-63.
Shimizu Saki, Kamata Masakazu, Kittipongdaja Panyamol, Chen Kevin N, Kim Sanggu, Pang Shen, Boyer Joshua, Qin F Xiao-Feng, An Dong Sung, Chen Irvin S Y Characterization of a potent non-cytotoxic shRNA directed to the HIV-1 co-receptor CCR5. Genetic vaccines and therapy
. 2009; 7(7): 8.
Kamata Masakazu, Susanto Melisa T, Chen Irvin S Y Enhanced transthyretin tetramer stability following expression of an amyloid disease transsuppressor variant in mammalian cells. The journal of gene medicine
. 2009; 11(2): 103-11.
Kamata Masakazu, Nagaoka Yoshiko, Chen Irvin S Y Reassessing the role of APOBEC3G in human immunodeficiency virus type 1 infection of quiescent CD4+ T-cells. PLoS pathogens
. 2009; 5(3): e1000342.
Morizono Kouki, Pariente Nonia, Xie Yiming, Chen Irvin S Y Redirecting lentiviral vectors by insertion of integrin-tageting peptides into envelope proteins. The journal of gene medicine
. 2009; 11(7): 549-58.
Wang Qiuwei, Zheng Jun-Ying, Kreth Jens, Yan Xinmin, Kamata Masakazu, Campbell Richard A, Xie Yiming, Chiu Robert, Berenson James R, Shi Wenyuan, Chen Irvin S Y, Pang Shen Regulation of prostate-specific antigen expression by the junctional adhesion molecule A. Urology
. 2009; 73(5): 1119-25.
Liang Min, Pariente Nonia, Morizono Kouki, Chen Irvin S Y Targeted transduction of CD34+ hematopoietic progenitor cells in nonpurified human mobilized peripheral blood mononuclear cells. The journal of gene medicine
. 2009; 11(3): 185-96.
Liang Min, Morizono Kouki, Pariente Nonia, Kamata Masakazu, Lee Benhur, Chen Irvin S Y Targeted transduction via CD4 by a lentiviral vector uses a clathrin-mediated entry pathway. Journal of virology
. 2009; 83(24): 13026-31.
Arokium Hubert, Kamata Masakazu, Chen Irvin Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances fas-induced apoptosis in human T cells. Journal of virology
. 2009; 83(21): 11283-97.
Pariente Nonia, Mao Si-Hua, Morizono Kouki, Chen Irvin S Y Efficient targeted transduction of primary human endothelial cells with dual-targeted lentiviral vectors. The journal of gene medicine
. 2008; 10(3): 242-8.
Kamata Masakazu, Watanabe Nobumoto, Nagaoka Yoshiko, Chen Irvin S Y Human immunodeficiency virus type 1 Vpr binds to the N lobe of the Wee1 kinase domain and enhances kinase activity for CDC2. Journal of virology
. 2008; 82(12): 5672-82.
Pariente Nonia, Morizono Kouki, Virk Mandeep S, Petrigliano Frank A, Reiter Robert E, Lieberman Jay R, Chen Irvin S Y A novel dual-targeted lentiviral vector leads to specific transduction of prostate cancer bone metastases in vivo after systemic administration. Molecular therapy : the journal of the American Society of Gene Therapy
. 2007; 15(11): 1973-81.
Wang Qiuwei, Wang Wei, Zheng Junying, Tabibian Sina, Xie Yiming, Song Jun, Waring Alan J, Chiu Robert, Yang Otto O, Chen Irvin S Y, Lehrer Robert I, Pang Shen Paradoxical effects of two theta-defensins on HIV type 1 infection. AIDS research and human retroviruses
. 2007; 23(4): 508-14.
An Dong Sung, Donahue Robert E, Kamata Masakazu, Poon Betty, Metzger Mark, Mao Si-Hua, Bonifacino Aylin, Krouse Allen E, Darlix Jean-Luc, Baltimore David, Qin F Xiao-Feng, Chen Irvin S Y Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates. Proceedings of the National Academy of Sciences of the United States of America
. 2007; 104(32): 13110-5.
An Dong Sung, Poon Betty, Ho Tsong Fang Raphael, Weijer Kees, Blom Bianca, Spits Hergen, Chen Irvin S Y, Uittenbogaart Christel H Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. Clinical and vaccine immunology : CVI
. 2007; 14(4): 391-6.
Poon Betty, Chang Michael A, Chen Irvin S Y Vpr is required for efficient Nef expression from unintegrated human immunodeficiency virus type 1 DNA.Journal of virology
. 2007; 81(19): 10515-23.
Kamata Masakazu, Wu Raymond P, An Dong Sung, Saxe Jonathan P, Damoiseaux Robert, Phelps Michael E, Huang Jing, Chen Irvin S Y Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV-1 Vpr induced cell death. Biochemical and biophysical research communications
. 2006; 348(3): 1101-6.
Sander William E, Metzger Mark E, Morizono Kouki, Bonifacino Aylin, Penzak Scott R, Xie Yi-Ming, Chen Irvin S Y, Bacon Jeffrey, Sestrich Stephen G, Szajek Lawrence P, Donahue Robert E Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates. Journal of nuclear medicine : official publication, Society of Nuclear Medicine
. 2006; 47(7): 1212-9.
Morizono Kouki, Ringpis Gene-Errol, Pariente Nonia, Xie Yiming, Chen Irvin S Y Transient low pH treatment enhances infection of lentiviral vector pseudotypes with a targeting Sindbis envelope. Virology
. 2006; 355(1): 71-81.
Zheng Junying, Xie Yiming, Campbell Richard, Song Jun, Wang Rose Q, Chiu Robert, Berenson James, Razi Miriam, Massachi Samira, Yang Otto O, Chen Irvin S Y, Pang Shen gp120-independent HIV infection of cells derived from the female reproductive tract, brain, and colon. Journal of acquired immune deficiency syndromes (1999)
. 2006; 43(2): 127-36.
Yuan Huidong, Fu Fenghua, Zhuo Jiaying, Wang Wei, Nishitani Junko, An Dong Sung, Chen Irvin S Y, Liu Xuan Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis. Oncogene
. 2005; 24(32): 5069-78.
Zheng Junying, Xie Yiming, Campbell Richard, Song Jun, Massachi Samira, Razi Miriam, Chiu Robert, Berenson James, Yang Otto O, Chen Irvin S Y, Pang Shen Involvement of claudin-7 in HIV infection of CD4(-) cells. Retrovirology
. 2005; 2(7): 79.
Morizono Kouki, Xie Yiming, Ringpis Gene-Errol, Johnson Mai, Nassanian Hoorig, Lee Benhur, Wu Lily, Chen Irvin S Y Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Nature medicine
. 2005; 11(3): 346-52.
Kung Sam K P, Bonifacino Aylin, Metzger Mark E, Ringpis Gene-Errol, Donahue Robert E, Chen Irvin S Y Lentiviral vector-transduced dendritic cells induce specific T cell response in a nonhuman primate model. Human gene therapy
. 2005; 16(4): 527-32.
Brooks David G, Cohen Michael D, Jamieson Beth D, Poon Betty, Kitchen Scott G, Chow Samson A, Chen Irvin S Y, Zack Jerome A, Koka Prasad S Rapid size dependent deletion of foreign gene sequences inserted into attenuated HIV-1 upon infection in vivo: implications for vaccine development. Current HIV research
. 2005; 3(4): 377-92.
Morizono Kouki, Chen Irvin S Y Targeted gene delivery by intravenous injection of retroviral vectors. Cell cycle (Georgetown, Tex.)
. 2005; 4(7): 854-6.
Yuan Huidong, Kamata Masakazu, Xie Yi-Ming, Chen Irvin S Y Increased levels of Wee-1 kinase in G(2) are necessary for Vpr- and gamma irradiation-induced G(2) arrest. Journal of virology
. 2004; 78(15): 8183-90.
Hui Eric Ka-Wai, Yap Ee Ming, An Dong Sung, Chen Irvin S Y, Nayak Debi P Inhibition of influenza virus matrix (M1) protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA. The Journal of general virology
. 2004; 85(Pt 7): 1877-84.
Donahue Robert E, Chen Irvin S Y Transgene-specific tolerance versus immune response. Blood
. 2004; 104(5): 1578-9; author reply 1579.
De Ugarte Daniel A, Morizono Kouki, Elbarbary Amir, Alfonso Zeni, Zuk Patricia A, Zhu Min, Dragoo Jason L, Ashjian Peter, Thomas Bert, Benhaim Prosper, Chen Irvin, Fraser John, Hedrick Marc H Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells, tissues, organs
. 2003; 174(3): 101-9.
Yuan Huidong, Xie Yi-Ming, Chen Irvin S Y Depletion of Wee-1 kinase is necessary for both human immunodeficiency virus type 1 Vpr- and gamma irradiation-induced apoptosis. Journal of virology
. 2003; 77(3): 2063-70.
An Dong Sung, Xie Yiming, Mao Si Hua, Morizono Kouki, Kung Sam K P, Chen Irvin S Y Efficient lentiviral vectors for short hairpin RNA delivery into human cells. Human gene therapy
. 2003; 14(12): 1207-12.
Poon Betty, Chen Irvin S Y Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA. Journal of virology
. 2003; 77(7): 3962-72.
Kung Sam K P, An Dong-Sung, Bonifacino Aylin, Metzger Mark E, Ringpis Gene-Errol, Mao Si-Hua, Chen Irvin S Y, Donahue Robert E Induction of transgene-specific immunological tolerance in myeloablated nonhuman primates using lentivirally transduced CD34+ progenitor cells. Molecular therapy : the journal of the American Society of Gene Therapy
. 2003; 8(6): 981-91.
Stewart Sheila A, Dykxhoorn Derek M, Palliser Deborah, Mizuno Hana, Yu Evan Y, An Dong Sung, Sabatini David M, Chen Irvin S Y, Hahn William C, Sharp Phillip A, Weinberg Robert A, Novina Carl D Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA (New York, N.Y.)
. 2003; 9(4): 493-501.
Morizono Kouki, De Ugarte Daniel A, Zhu Min, Zuk Pat, Elbarbary Amir, Ashjian Peter, Benhaim Prosper, Chen Irvin S Y, Hedrick Marc H Multilineage cells from adipose tissue as gene delivery vehicles. Human gene therapy
. 2003; 14(1): 59-66.
Yang Otto O, Nguyen Phuong Thi, Kalams Spyros A, Dorfman Tanya, GÃ¶ttlinger Heinrich G, Stewart Sheila, Chen Irvin S Y, Threlkeld Steven, Walker Bruce D Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes. Journal of virology
. 2002; 76(4): 1626-31.
Chow Yen-Hung, Yu Duan, Zhang Jun-Ying, Xie Yiming, Wei O Lu-Chen, Chiu Christopher, Foroohar Mani, Yang Otto O, Park No-Hee, Chen Irvin S Y, Pang Shen gp120-Independent infection of CD4(-) epithelial cells and CD4(+) T-cells by HIV-1. Journal of acquired immune deficiency syndromes (1999)
. 2002; 30(1): 1-8.
Morizono K, Bristol G, Xie YM, Kung SK, Chen IS Antibody-directed targeting of retroviral vectors via cell surface antigens. Journal of virology.
. 2001; 75(17): 8016-20.
Amado SP, Chen ISY Biomedicine: Lentiviral Vectors-The Promise of Gene Therapy Within Reach?. Science 1999; 285, 5428: 674-676.
Frenkel LM, Mullins JI, Learn GH, Manns-Arcuino L, Herring BL, Kalish ML, Steketee RW, Thea DM, Nichols JE, Liu SL, Harmache A, He X, Muthui D, Madan A, Hood L, Haase AT, Zupancic M, Staskus K, Wolinsky S, Krogstad P, Zhao J, Chen I, Koup R, Ho D, Korber B, Apple RJ, Coombs RW, Pahwa S, Roberts NJ Genetic evaluation of suspected cases of transient HIV-1 infection of infants. Science.
. 1998; 280(5366): 1073-7.
Poon B, Ferbas KG, Stewart SA, Chen ISY HIV-1 Vpr in virions induces cell cycle arrest and is insensitive to antiretroviral agents. Science 1998; 281: 266-269.
An DS, Koyanagi Y, Zhao JQ, Akkina R, Bristol G, Yamamoto N, Zack JA, Chen IS High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells. Journal of virology.
. 1997; 71(2): 1397-404.
Stewart SA, Poon B, Jowett JB, Chen IS Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. Journal of virology.
. 1997; 71(7): 5579-92.
Cao Y, Krogstad P, Korber BT, Koup RA, Muldoon M, Macken C, Song LJ, Jin Z, Zhao JQ, Clapp S, Chen ISY, Ho DD, Ammann AJ, and the Ariel Project Investigators Maternal HIV-1 viral load and vertical transmission of infection. Nature Medicine 1997; 3, 5: 549-552.
Withers-Ward ES, Amado RG, Koka PS, Jamieson BD, Kaplan AH, Chen IS, Zack JA Transient renewal of thymopoiesis in HIV-infected human thymic implants following antiviral therapy. Nature medicine.
. 1997; 3(10): 1102-9.
Camerini D, Planelles V, Chen ISY D26 antigen and HIV fusion?. Science 1994; 264: 1160-1161.
Aldrovandi GM, Feuer G, Gao L, Kristeva M, Chen ISY, Zack JA An animal model for virus pathogenesis. Nature 1993; 363: 732-736.
Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell.
. 1990; 61(2): 213-22.
O’Brien WA, Koyanagi Y, Namazie A, Zhao JQ, Diagne A, Idler K, Zack JA, Chen IS HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature.
. 1990; 348(6296): 69-73.
Pang S, Koyanagi Y, Miles S, Wiley C, Vinters HV, Chen IS High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature.
. 1990; 343(6253): 85-9.
Lee H, Swanson P, Shorty VS, Zack JA, Rosenblatt JD, Chen ISY High rate of HTLV-11 infection in seropositive IV drug abusers from New Orleans. Science 1989; 244: 471-475.
Zack JA, Cann AJ, Lugo JP, Chen ISY AIDS virus production from infected peripheral blood T cells following HTLV-1-induced mitogenic stimulation. Science 1988; 240: 1026-1029.
Koyanagi Y, O’Brien WA, Zhao JQ, Golde DW, Gasson JC, Chen IS Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science.
. 1988; 241(4873): 1673-5.
Rosenblatt JD, Cann AJ, Slamon DJ, Smalberg IS, Shah NP, Fujii J, Wachsman W, Chen ISY HTLV-11 trans-activation is regulated by two overlapping nonstructural genes. Science 1988; 240: 916-919.
Liang Min, Yan Ming, Lu Yunfeng, Chen Irvin S Y Retargeting vesicular stomatitis virus glycoprotein pseudotyped lentiviral vectors with enhanced stability by in situ synthesized polymer shell. Human gene therapy methods
. 2013; 24(1): 11-8.
Ringpis Gene-Errol E, Shimizu Saki, Arokium Hubert, Camba-ColÃ³n Joanna, Carroll Maria V, Cortado Ruth, Xie Yiming, Kim Patrick Y, Sahakyan Anna, Lowe Emily L, Narukawa Munetoshi, Kandarian Fadi N, Burke Bryan P, Symonds Geoff P, An Dong Sung, Chen Irvin S Y, Kamata Masakazu Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice. PloS one
. 2012; 7(12): e53492.