Irvin Sy Chen
Professor, MIMG, University of California Los Angeles
Professor, Medicine, University of California Los Angeles
615 Charles E. Young Dr. South
BSRB, Rm 161
Los Angeles, CA 90095
615 Charles E. Young Dr. South
BSRB, Rm 173
Los Angeles, CA 90095
Work Phone Number:
Co-Leader, Pilot and Collaborative Translational Clinical Studies Program
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.
- Suryawanshi GW, Arokium H, Kim S, Khamaikawin W, Lin S, Shimizu S, Chupradit K, Lee Y, Xie Y, Guan X, Suryawanshi V, Presson AP, An DS, Chen ISY. Longitudinal clonal tracking in humanized mice reveals sustained polyclonal repopulation of gene-modified human-HSPC despite vector integration bias.. Stem cell research & therapy, 2021.
- Wen J, Cheever T, Wang L, Wu D, Reed J, Mascola J, Chen X, Liu C, Pegu A, Sacha JB, Lu Y, Haigwood NL, Chen ISY. Improved delivery of broadly neutralizing antibodies by nanocapsules suppresses SHIV infection in the CNS of infant rhesus macaques.. PLoS pathogens, 2021.
- Zhen A, Carrillo MA, Mu W, Rezek V, Martin H, Hamid P, Chen ISY, Yang OO, Zack JA, Kitchen SG. Robust CAR-T memory formation and function via hematopoietic stem cell delivery.. PLoS pathogens, 2021.
- Wen J, Wang L, Ren J, Kranz E, Chen S, Wu D, Kanazawa T, Chen I, Lu Y, Kamata M. Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model.. Journal for immunotherapy of cancer, 2021.
- Barber-Axthelm IM, Barber-Axthelm V, Sze KY, Zhen A, Suryawanshi GW, Chen IS, Zack JA, Kitchen SG, Kiem HP, Peterson CW. Stem cell-derived CAR T cells traffic to HIV reservoirs in macaques.. JCI insight, 2021.
- Suryawanshi GW, Khamaikawin W, Wen J, Shimizu S, Arokium H, Xie Y, Wang E, Kim S, Choi H, Zhang C, Yu H, Presson AP, Kim N, An DS, Chen ISY, Kim S. The clonal repopulation of HSPC gene modified with anti-HIV-1 RNAi is not affected by preexisting HIV-1 infection.. Science advances, 2020.
- Qin M, Wang L, Wu D, Williams CK, Xu D, Kranz E, Guo Q, Guan J, Vinters HV, Lee Y, Xie Y, Luo Y, Sun G, Sun X, He Z, Lu Y, Kamata M, Wen J, Chen ISY. Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.. Frontiers in immunology, 2020.
- Wu D, Yang Y, Xu P, Xu D, Liu Y, Castillo R, Yan R, Ren J, Zhou G, Liu C, Qin M, Du J, Hou L, Chen I, Kang C, Jin L, Wen J, Chen W, Lu Y. Real-Time Quantification of Cell Internalization Kinetics by Functionalized Bioluminescent Nanoprobes.. Advanced materials (Deerfield Beach, Fla.), 2019.
- Wen J, Wu D, Qin M, Liu C, Wang L, Xu D, Vinters HV, Liu Y, Kranz E, Guan X, Sun G, Sun X, Lee Y, Martinez-Maza O, Widney D, Lu Y, Chen ISY, Kamata M. Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice.. Nature biomedical engineering, 2019.
- Xu D, Wu D, Qin M, Nih LR, Liu C, Cao Z, Ren J, Chen X, He Z, Yu W, Guan J, Duan S, Liu F, Liu X, Li J, Harley D, Xu B, Hou L, Chen ISY, Wen J, Chen W, Pourtaheri S, Lu Y. Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration.. Advanced materials (Deerfield Beach, Fla.), 2019.
- Wu D, Qin M, Xu D, Wang L, Liu C, Ren J, Zhou G, Chen C, Yang F, Li Y, Zhao Y, Huang R, Pourtaheri S, Kang C, Kamata M, Chen ISY, He Z, Wen J, Chen W, Lu Y. A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System.. Advanced materials (Deerfield Beach, Fla.), 2019.
- Zhen A, Peterson CW, Carrillo MA, Reddy SS, Youn CS, Lam BB, Chang NY, Martin HA, Rick JW, Kim J, Neel NC, Rezek VK, Kamata M, Chen ISY, Zack JA, Kiem HP, Kitchen SG. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.. PLoS pathogens, 2017.
- Khamaikawin W, Shimizu S, Kamata M, Cortado R, Jung Y, Lam J, Wen J, Kim P, Xie Y, Kim S, Arokium H, Presson AP, Chen ISY, An DS. Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1.. Molecular therapy. Methods & clinical development, 2017.
- Chan J, Kim PY, Kranz E, Nagaoka Y, Lee Y, Wen J, Elsaesser HJ, Qin M, Brooks DG, Ringpis GE, Chen ISY, Kamata M. Purging Exhausted Virus-Specific CD8 T Cell Phenotypes by Somatic Cell Reprogramming.. AIDS research and human retroviruses, 2017.
- Suryawanshi GW, Xu S, Xie Y, Chou T, Kim N, Chen ISY, Kim S. Bidirectional Retroviral Integration Site PCR Methodology and Quantitative Data Analysis Workflow.. Journal of visualized experiments : JoVE, 2017.
- Ali A, Kitchen SG, Chen ISY, Ng HL, Zack JA, Yang OO. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies.. Journal of virology, 2016.
- Wen J, Yan M, Liu Y, Li J, Xie Y, Lu Y, Kamata M, Chen IS. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules.. PloS one, 2016.
- Zhen A, Kamata M, Rezek V, Rick J, Levin B, Kasparian S, Chen IS, Yang OO, Zack JA, Kitchen SG. HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells.. Molecular therapy : the journal of the American Society of Gene Therapy, 2015.
- Yan M, Wen J, Liang M, Lu Y, Kamata M, Chen IS. Modulation of Gene Expression by Polymer Nanocapsule Delivery of DNA Cassettes Encoding Small RNAs.. PloS one, 2015.
- Kamata M, Kim PY, Ng HL, Ringpis GE, Kranz E, Chan J, O'Connor S, Yang OO, Chen IS. Ectopic expression of anti-HIV-1 shRNAs protects CD8(+) T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation.. Biochemical and biophysical research communications, 2015.
- Shimizu S, Ringpis GE, Marsden MD, Cortado RV, Wilhalme HM, Elashoff D, Zack JA, Chen IS, An DS. RNAi-Mediated CCR5 Knockdown Provides HIV-1 Resistance to Memory T Cells in Humanized BLT Mice.. Molecular therapy. Nucleic acids, 2015.
- Arokium H, Kamata M, Kim S, Kim N, Liang M, Presson AP, Chen IS. Deep sequencing reveals low incidence of endogenous LINE-1 retrotransposition in human induced pluripotent stem cells.. PloS one, 2014.
- Pang S, Pokomo L, Chen K, Kamata M, Mao SH, Zhang H, Razi E, An DS, Chen IS. High-throughput screening of effective siRNAs using luciferase-linked chimeric mRNA.. PloS one, 2014.
- Kim S, Kim N, Presson AP, Metzger ME, Bonifacino AC, Sehl M, Chow SA, Crooks GM, Dunbar CE, An DS, Donahue RE, Chen IS. Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study.. Cell stem cell, 2014.
- Wolstein O, Boyd M, Millington M, Impey H, Boyer J, Howe A, Delebecque F, Cornetta K, Rothe M, Baum C, Nicolson T, Koldej R, Zhang J, Keech N, Camba Colón J, Breton L, Bartlett J, An DS, Chen IS, Burke B, Symonds GP. Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor.. Molecular therapy. Methods & clinical development, 2014.
- Morizono K, Chen IS. Role of phosphatidylserine receptors in enveloped virus infection.. Journal of virology, 2014.
- Leoh LS, Morizono K, Kershaw KM, Chen IS, Penichet ML, Daniels-Wells TR. Gene delivery in malignant B cells using the combination of lentiviruses conjugated to anti-transferrin receptor antibodies and an immunoglobulin promoter.. The journal of gene medicine, 2014.
- Liang M, Yan M, Lu Y, Chen IS. Retargeting vesicular stomatitis virus glycoprotein pseudotyped lentiviral vectors with enhanced stability by in situ synthesized polymer shell.. Human gene therapy methods, 2013.
- Ringpis GE, Shimizu S, Arokium H, Camba-Colón J, Carroll MV, Cortado R, Xie Y, Kim PY, Sahakyan A, Lowe EL, Narukawa M, Kandarian FN, Burke BP, Symonds GP, An DS, Chen IS, Kamata M. Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.. PloS one, 2012.
- Yan M, Liang M, Wen J, Liu Y, Lu Y, Chen IS. Single siRNA nanocapsules for enhanced RNAi delivery.. Journal of the American Chemical Society, 2012.
- Presson AP, Kim N, Xiaofei Y, Chen IS, Kim S. Methodology and software to detect viral integration site hot-spots.. BMC bioinformatics, 2011.
- Morizono K, Chen IS. Receptors and tropisms of envelope viruses.. Current opinion in virology, 2011.
- Morizono K, Xie Y, Olafsen T, Lee B, Dasgupta A, Wu AM, Chen IS. The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.. Cell host & microbe, 2011.
- Chen IS. Introduction. The UCLA AIDS Institute.. Immunologic research, 2010.
- Kamata M, Liu S, Liang M, Nagaoka Y, Chen IS. 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.
- Kim S, Kim N, Presson AP, An DS, Mao SH, Bonifacino AC, Donahue RE, Chow SA, Chen IS. High-throughput, sensitive quantification of repopulating hematopoietic stem cell clones.. Journal of virology, 2010.
- Kamata M, Liang M, Liu S, Nagaoka Y, Chen IS. Live cell monitoring of hiPSC generation and differentiation using differential expression of endogenous microRNAs.. PloS one, 2010.
- Morizono K, Ku A, Xie Y, Harui A, Kung SK, Roth MD, Lee B, Chen IS. 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.
- Liang M, Kamata M, Chen KN, Pariente N, An DS, Chen IS. 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.
- Shimizu S, Hong P, Arumugam B, Pokomo L, Boyer J, Koizumi N, Kittipongdaja P, Chen A, Bristol G, Galic Z, Zack JA, Yang O, Chen IS, Lee B, An DS. A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model.. Blood, 2009.
- Liang M, Morizono K, Pariente N, Kamata M, Lee B, Chen IS. Targeted transduction via CD4 by a lentiviral vector uses a clathrin-mediated entry pathway.. Journal of virology, 2009.
- Arokium H, Kamata M, Chen I. 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.
- Morizono K, Xie Y, Helguera G, Daniels TR, Lane TF, Penichet ML, Chen IS. A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide.. The journal of gene medicine, 2009.
- Morizono K, Pariente N, Xie Y, Chen IS. Redirecting lentiviral vectors by insertion of integrin-tageting peptides into envelope proteins.. The journal of gene medicine, 2009.
- Shimizu S, Kamata M, Kittipongdaja P, Chen KN, Kim S, Pang S, Boyer J, Qin FX, An DS, Chen IS. Characterization of a potent non-cytotoxic shRNA directed to the HIV-1 co-receptor CCR5.. Genetic vaccines and therapy, 2009.
- Kamata M, Nagaoka Y, Chen IS. Reassessing the role of APOBEC3G in human immunodeficiency virus type 1 infection of quiescent CD4+ T-cells.. PLoS pathogens, 2009.
- Liang M, Pariente N, Morizono K, Chen IS. Targeted transduction of CD34+ hematopoietic progenitor cells in nonpurified human mobilized peripheral blood mononuclear cells.. The journal of gene medicine, 2009.
- Kamata M, Susanto MT, Chen IS. Enhanced transthyretin tetramer stability following expression of an amyloid disease transsuppressor variant in mammalian cells.. The journal of gene medicine, 2009.
- Wang Q, Zheng JY, Kreth J, Yan X, Kamata M, Campbell RA, Xie Y, Chiu R, Berenson JR, Shi W, Chen IS, Pang S. Regulation of prostate-specific antigen expression by the junctional adhesion molecule A.. Urology, 2008.
- Kamata M, Watanabe N, Nagaoka Y, Chen IS. 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.
- Pariente N, Mao SH, Morizono K, Chen IS. Efficient targeted transduction of primary human endothelial cells with dual-targeted lentiviral vectors.. The journal of gene medicine, 2008.
- Brakenhielm E, Burton JB, Johnson M, Chavarria N, Morizono K, Chen I, Alitalo K, Wu L. Modulating metastasis by a lymphangiogenic switch in prostate cancer.. International journal of cancer, 2007.
- An DS, Donahue RE, Kamata M, Poon B, Metzger M, Mao SH, Bonifacino A, Krouse AE, Darlix JL, Baltimore D, Qin FX, Chen IS. 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.
- Poon B, Chang MA, Chen IS. Vpr is required for efficient Nef expression from unintegrated human immunodeficiency virus type 1 DNA.. Journal of virology, 2007.
- Pariente N, Morizono K, Virk MS, Petrigliano FA, Reiter RE, Lieberman JR, Chen IS. 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.
- Wang Q, Wang W, Zheng J, Tabibian S, Xie Y, Song J, Waring AJ, Chiu R, Yang OO, Chen IS, Lehrer RI, Pang S. Paradoxical effects of two theta-defensins on HIV type 1 infection.. AIDS research and human retroviruses, 2007.
- An DS, Poon B, Ho Tsong Fang R, Weijer K, Blom B, Spits H, Chen IS, Uittenbogaart CH. 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.
- Zheng J, Xie Y, Campbell R, Song J, Wang RQ, Chiu R, Berenson J, Razi M, Massachi S, Yang OO, Chen IS, Pang S. gp120-independent HIV infection of cells derived from the female reproductive tract, brain, and colon.. Journal of acquired immune deficiency syndromes (1999), 2006.
- Morizono K, Ringpis GE, Pariente N, Xie Y, Chen IS. Transient low pH treatment enhances infection of lentiviral vector pseudotypes with a targeting Sindbis envelope.. Virology, 2006.
- Kamata M, Wu RP, An DS, Saxe JP, Damoiseaux R, Phelps ME, Huang J, Chen IS. Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV-1 Vpr induced cell death.. Biochemical and biophysical research communications, 2006.
- Feeley BT, Conduah AH, Sugiyama O, Krenek L, Chen IS, Lieberman JR. In vivo molecular imaging of adenoviral versus lentiviral gene therapy in two bone formation models.. Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2006.
- An DS, Qin FX, Auyeung VC, Mao SH, Kung SK, Baltimore D, Chen IS. Optimization and functional effects of stable short hairpin RNA expression in primary human lymphocytes via lentiviral vectors.. Molecular therapy : the journal of the American Society of Gene Therapy, 2006.
- Zheng J, Xie Y, Campbell R, Song J, Massachi S, Razi M, Chiu R, Berenson J, Yang OO, Chen IS, Pang S. Involvement of claudin-7 in HIV infection of CD4(-) cells.. Retrovirology, 2005.
- Brooks DG, Cohen MD, Jamieson BD, Poon B, Kitchen SG, Chow SA, Chen IS, Zack JA, Koka PS. 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.
- Morizono K, Chen IS. Targeted gene delivery by intravenous injection of retroviral vectors.. Cell cycle (Georgetown, Tex.), 2005.
- Kung SK, Bonifacino A, Metzger ME, Ringpis GE, Donahue RE, Chen IS. Lentiviral vector-transduced dendritic cells induce specific T cell response in a nonhuman primate model.. Human gene therapy, 2005.
- Sugiyama O, An DS, Kung SP, Feeley BT, Gamradt S, Liu NQ, Chen IS, Lieberman JR. Lentivirus-mediated gene transfer induces long-term transgene expression of BMP-2 in vitro and new bone formation in vivo.. Molecular therapy : the journal of the American Society of Gene Therapy, 2005.
- Morizono K, Xie Y, Ringpis GE, Johnson M, Nassanian H, Lee B, Wu L, Chen IS. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection.. Nature medicine, 2005.
- Zheng J, Yang OO, Xie Y, Campbell R, Chen IS, Pang S. Ethanol stimulation of HIV infection of oral epithelial cells.. Journal of acquired immune deficiency syndromes (1999), 2004.
- Yuan H, Kamata M, Xie YM, Chen IS. Increased levels of Wee-1 kinase in G(2) are necessary for Vpr- and gamma irradiation-induced G(2) arrest.. Journal of virology, 2004.
- Hui EK, Yap EM, An DS, Chen ISY, Nayak DP. 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.
- Kung SK, An DS, Bonifacino A, Metzger ME, Ringpis GE, Mao SH, Chen IS, Donahue RE. 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.
- An DS, Xie Y, Mao SH, Morizono K, Kung SK, Chen IS. Efficient lentiviral vectors for short hairpin RNA delivery into human cells.. Human gene therapy, 2003.
- Poon B, Chen IS. Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA.. Journal of virology, 2003.
- Yuan H, Xie YM, Chen IS. Depletion of Wee-1 kinase is necessary for both human immunodeficiency virus type 1 Vpr- and gamma irradiation-induced apoptosis.. Journal of virology, 2003.
- De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P, Chen I, Fraser J, Hedrick MH. Comparison of multi-lineage cells from human adipose tissue and bone marrow.. Cells, tissues, organs, 2003.
- Morizono K, De Ugarte DA, Zhu M, Zuk P, Elbarbary A, Ashjian P, Benhaim P, Chen IS, Hedrick MH. Multilineage cells from adipose tissue as gene delivery vehicles.. Human gene therapy, 2003.
- Chow YH, Yu D, Zhang JY, Xie Y, Wei OL, Chiu C, Foroohar M, Yang OO, Park NH, Chen IS, Pang S. gp120-Independent infection of CD4(-) epithelial cells and CD4(+) T-cells by HIV-1.. Journal of acquired immune deficiency syndromes (1999), 2002.
- Yang OO, Nguyen PT, Kalams SA, Dorfman T, Göttlinger HG, Stewart S, Chen IS, Threlkeld S, Walker BD. Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes.. Journal of virology, 2002.