Dong Sung An, MD, PhD

Dr. Dong Sung An is a professor at the UCLA School of Nursing and a faculty member at the UCLA AIDS Institute. His research focuses on developing anti HIV-1 gene therapy for HIV diseases. HIV infection has caused a devastating impact on humanity for more than 40 years. It still affects more than 39 millions of people worldwide and 1.2 millions of people in US. An effective vaccine is not available. Highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality of HIV in all parts of the world. However, the efficacy of such treatment is limited by the presence of chronically HIV infected reservoirs, which prevent cure and force the life-long treatment. 
 
My research team investigates a novel HIV therapeutic strategy by genetic engineering human blood stem cells. We develop efficient gene delivery systems to introduce anti-HIV genes into blood stem cells and offer life-long protection against HIV. My translational research aims to bring basic science findings to the clinic for HIV cure. 

Areas of Scholarly Expertise and Interest

HIV/AIDS, stem cell based gene therapy. 

Faculty Research and Clinical Expertise

Research: Developing hematopoietic stem cell based gene therapy strategies for treating HIV infected patients. My research team investigates efficient introduction of protective genes against HIV into target cells and offer protection against HIV. My research aims to bring basic science findings to the clinic.

Education

Yamaguchi University School of Medicine, M.D., 1993, Medicine

Tokyo Medical and Dental University, PhD 1997, Virology

Honors and Awards

Soujinkan Award, Yamaguchi University School of Medicine, 2004

Publications

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 Res Ther. 2021 Oct 7;12(1):528. doi: 10.1186/s13287-021-02601-5. PMID: 34620229. 

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. Sci Adv. 2020 Jul 22;6(30):eaay9206. doi: 10.1126/sciadv.aay9206. eCollection 2020 Jul. PMID: 32766447. 

Zhu Y, Smith DJ, Zhou Y, Li YR, Yu J, Lee D, Wang YC, Di Biase S, Wang X, Hardoy C, Ku J, Tsao T, Lin LJ, Pham AT, Moon H, McLaughlin J, Cheng D, Hollis RP, Campo-Fernandez B, Urbinati F, Wei L, Pang L, Rezek V, Berent-Maoz B, Macabali MH, Gjertson D, Wang X, Galic Z, Kitchen SG, An DS, Hu-Lieskovan S, Kaplan-Lefko PJ, De Oliveira SN, Seet CS, Larson SM, Forman SJ, Heath JR, Zack JA, Crooks GM, Radu CG, Ribas A, Kohn DB, Witte ON, Yang L. Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.  Cell Stem Cell. 2019 Oct 3;25(4):542-557.e9. doi: 10.1016/j.stem.2019.08.004. Epub 2019 Sep 5. PMID: 31495780.

Ladinsky MS, Khamaikawin W, Jung Y, Lin S, Lam J, An DS, Bjorkman PJ, Kieffer C.  Mechanisms of virus dissemination in bone marrow of HIV-1-infected humanized BLT mice.  Elife. 2019 Oct 28;8:e46916. doi: 10.7554/eLife.46916. PMID: 31657719. 

Srikanth S, Woo JS, Wu B, El-Sherbiny YM, Leung J, Chupradit K, Rice L, Seo GJ, Calmettes G, Ramakrishna C, Cantin E, An DS; Sun R, Wu TT, Jung JU, Savic S, Gwack Y. The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum. Nature Immunology. 2019 Feb; 20(2):152-162. doi: 10.1038/s41590-018-0287-8. Epub 2019 Jan 14.

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. Mol Ther Methods Clin Dev. 2017 Dec 1; 9:23-32. doi: 10.1016/j.omtm.2017.11.008. eCollection 2018 Jun 15.

Smith DJ, Lin LJ, Moon H, Pham AT, Wang X, Liu S, Ji S, Rezek V, Shimizu S, Ruiz M, Lam J, Janzen DM, Memarzadeh S, Kohn DB, Zack JA, Kitchen SG, An DS; Yang L. Propagating Humanized BLT Mice for the Study of Human Immunology and Immunotherapy. Stem Cells Dev. 2016 Dec 15; 25(24):1863-1873. Epub 2016 Oct 18.

Burke BP, Levin BR, Zhang J, Sahakyan A, Boyer J, Carroll MV, Colón JC, Keech N, Rezek V, Bristol G, Eggers E, Cortado R, Boyd MP, Impey H, Shimizu S, Lowe EL, Ringpis GE, Kim SG, Vatakis DN, Breton LR, Bartlett JS, Chen IS, Kitchen SG, An DS; Symonds GP. Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector. Mol Ther Nucleic Acids. 2015 Apr 14; 4:e236. doi: 10.1038/mtna.2015.10.

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. Mol Ther Nucleic Acids. 2015 Feb 17; 4:e227. doi: 10.1038/mtna.2015.3.

Liu H, Cadaneanu RM, Lai K, Zhang B, Huo L, An DS; Li X, Lewis MS, Garraway IP. Differential gene expression profiling of functionally and developmentally distinct human prostate epithelial populations. Prostate. 2015 May; 75(7):764-76. doi: 10.1002/pros.22959. Epub 2015 Feb 7.

Sato K, Takeuchi JS, Misawa N, Izumi T, Kobayashi T, Kimura Y, Iwami S, Takaori-Kondo A, Hu WS, Aihara K, Ito M, An DS; Pathak VK, Koyanagi Y.APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model. PLoS Pathog. 2014 Oct 16;10(10):e1004453. doi: 10.1371/journal.ppat.1004453. eCollection 2014 Oct.

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. Mol Ther Methods Clin Dev. 2014 Feb 12; 1:11. doi: 10.1038/mtm.2013.11. eCollection 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 May 15; 9(5):e96445. doi: 10.1371/journal.pone.0096445. eCollection 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 Apr 3; 14(4):473-85. doi: 10.1016/j.stem.2013.12.012.

Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, An DS; Baltimore D. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med. 2014 Mar; 20(3):296-300. doi: 10.1038/nm.3471. Epub 2014 Feb 9.

Sato K, Misawa N, Iwami S, Satou Y, Matsuoka M, Ishizaka Y, Ito M, Aihara K, An DS; Koyanagi Y. HIV-1 Vpr accelerates viral replication during acute infection by exploitation of proliferating CD4+ T cells in vivo. PLoS Pathog. 2013 Dec; 9(12):e1003812. doi: 10.1371/journal.ppat.1003812. Epub 2013 Dec 5.

Kim KD, Srikanth S, Tan YV, Yee MK, Jew M, Damoiseaux R, Jung ME, Shimizu S, An DS; Ribalet B, Waschek JA, Gwack Y. Calcium signaling via Orai1 is essential for induction of the nuclear orphan receptor pathway to drive Th17 differentiation. J Immunol. 2014 Jan 1; 192(1):110-22. doi: 10.4049/jimmunol.1302586. Epub 2013 Dec 4.

Sellers SE, Dumitriu B, Morgan MJ, Hughes WM, Wu CO, Raghavarchari N, Yang Y, Uchida N, Tisdale JF, An DS; Chen IS, Hematti P, Donahue RE, Larochelle A, Young NS, Calado RT, Dunbar CE. No impact of lentiviral transduction on hematopoietic stem/progenitor cell telomere length or gene expression in the rhesus macaque model. Mol Ther. 2014 Jan; 22(1):52-8. doi: 10.1038/mt.2013.168. Epub 2013 Jul 18.

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; 7(12):e53492. doi: 10.1371/journal.pone.0053492. Epub 2012 Dec 31.

Palomares K, Vigant F, Van Handel B, Pernet O, Chikere K, Hong P, Sherman SP, Patterson M, An DS; Lowry WE, Mikkola HK, Morizono K, Pyle AD, Lee B. Nipah virus envelope-pseudotyped lentiviruses efficiently target ephrinB2-positive stem cell populations in vitro and bypass the liver sink when administered in vivo. J Virol. 2013 Feb; 87(4):2094-108. doi: 10.1128/JVI.02032-12. Epub 2012 Nov 28. Erratum in: J Virol. 2013 Apr;87(8):4794. 

Hur EM, Patel SN, Shimizu S, Rao DS, Gnanapragasam PN, An DS; Yang L, Baltimore D. Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice.  Blood. 2012 Nov 29; 120(23):4571-82. doi: 10.1182/blood-2012-04-422303. Epub 2012 Oct 11.

Suree N, Koizumi N, Sahakyan A, Shimizu S, An DS; A novel HIV-1 reporter virus with a membrane-bound Gaussia princeps luciferase. J Virol Methods. 2012 Jul; 183(1):49-56. Epub 2012 Mar 31.

Sato K, Misawa N, Fukuhara M, Iwami S, An DS; Ito M, Koyanagi Y. Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2 and CD4 in humanized mice. J Virol. 2012 May; 86(9):5000-13. Epub 2012 Feb 22.

Marsden MD, Kovochich M, Suree N, Shimizu S, Mehta R, Cortado R, Bristol G, An DS; Zack JA.  HIV latency in the humanized BLT mouse. J Virol. 2012 Jan; 86(1):339-47. Epub 2011 Nov 9.

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. J Virol. 2010 Sep 15.

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. J Gene Med. 2010 Mar; 12(3):255-65.

Shimizu, S., Hong, P., Arumugan, B., Pokomo, L., Boyer, J., Koizumi, N., Kittipongdaja, P., Chen, A., Bristol, G., Galic, Z., Zack, J., Yang, O., Chen, I., Lee, B. and An DS.  A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model. Blood. 2010 Feb 25; 115(8):1534-44. Epub 2009 Dec 17.

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. Genet Vaccines Ther. 2009 Jun 10; 7(1):8.

Burton JB, Priceman SJ, Sung JL, Brakenhielm E, An DS; Pytowski B, Alitalo K, Wu L.  Suppression of Prostate Cancer Nodal and Systemic Metastasis by Blockade of the Lymphangiogenic Axis. Cancer Research; 68: (19). October 1, 2008.

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. Proc Natl Acad Sci U S A; 2007 Aug 1.

An DS; Poon B, Fang RH, Weijer K, Blom B, Spits H, Chen IS, Uittenbogaart CH. The Human immune system (HIS) RAG-/-{gamma}c-/- mouse, a novel chimeric mouse model for HIV-1 infection. Clin Vaccine Immunol. 2007 Feb 21.

Hsu WK, Sugiyama OS, Park SH, Conduah A, Feeley BT, Liu NQ, Krenek L, Virk MS, An DS; Chen IS, Lieberman JR. Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats. Bone. 2007 Jan 19.

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. Biochem Biophys Res Commun. 2006 Aug 2.

An DS; Qin XF, Auyeung VC, Mao SH, Kung SKP, Baltimore D, and Chen ISY. Optimization and functional effects of stable short hairpin RNA expression in primary human lymphocytes via lentiviral vectors. Molecular Therapy, July14. 2006.

Dykes C, Wang J, Jin X, Planelles V, An DS; Tallo A, Huang Y, Wu H, Demeter LM. Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture. J Clin Microbiol. 2006 Jun; 44(6):1930-4

Yuan H, Fu F, Zhuo J, Wang W, Nishitani J, An DS; Chen IS, Liu X. Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis.  Oncogene. 2005 Apr 25.

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. 2005 Mar; 11(3):390-8.

DeHart JL, Andersen JL, Zimmerman ES, Ardon D, An DS; Blackett J, Kim B, and Planelles V. The Ataxia Telangiectasia-Mutated and Rad3-Related Protein Is Dispensable for Retroviral Integration Journal of Virology. 2005. 79: 1389-1396. 

Hui EK, Yap EM, An DS; Chen IS, Nayak DP. Inhibition of influenza virus matrix (M1) protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA.  Journal Gen Virol.  2004 Jul;85 (Pt 7):1877-84.

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. 2003 Dec; 8(6):981-91. 

An DS; Xie Y, Mao SH, Morizono K, Kung SK, Chen ISY. Efficient lentiviral vectors for short hairpin RNA delivery into human cells.  Human Gene Therapy. 2003 Aug 10; 14(12):1207-12.

Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, An DS; Sabatini DM, Chen ISY, Hahn WC, Sharp PA, Weinberg RA, Novina CD. Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA. 2003 Apr; 9(4):493-501. 

Qin XF*, An DS*; Chen ISY, Baltimore D. Inhibiting HIV-1 infection in human T-cells by lentiviral-mediated delivery of siRNA against CCR5. Proceedings of National Academy of Sciences of the United States of America.  2003 Jan 7; 100(1):183-8. (*These authors contributed equally to this work.)

Donahue RE, Sorrentino BP, Hawley RG, An DS; Chen IS, Wersto RP. Fibronectin Fragment CH-296 Inhibits Apoptosis and Enhances ex Vivo Gene Transfer by Murine Retrovirus and Human Lentivirus Vectors Independent of Viral Tropism in Nonhuman Primate CD34 (+) Cells. Molecular Therapy. 2001 Mar; 3(3):359-67.

An DS; Kung SK, Bonifacino A, Wersto RP, Metzger ME, Agricola BA, Mao SH, Chen IS, Donahue RE. Lentivirus vector-mediated hematopoietic stem cell gene transfer of common gamma-chain cytokine receptor in rhesus macaques. Journal of Virology. 2001 Apr; 75(8):3547-55.

An DS; Xie Ym, Chen IS. Envelope gene of the human endogenous retrovirus HERV-W encodes a functional retrovirus envelope. Journal of Virology. 2001 Apr; 75(7):3488-9.

Pang S, Yu D, An DS; Baldwin GC, Xie Y, Poon B, Chow YH, Park NH, Chen IS. Human immunodeficiency virus env-independent infection of human CD4 (-) cells Journal of Virology. 2000 Dec; 74(23):10994-1000.

Kung K. P, An DS; Chen ISY.  A Murine Leukemia Virus (MuLV) Long Terminal Repeat Derived from Rhesus Macaques in the Context of a Lentivirus Vector and MuLV gag Sequence Results in High-Level Gene Expression in Human T Lymphocytes. Journal of Virology. 74:3668-3681. April 2000.

An DS; Wersto RP, Agricola BA, Metzger ME, Lu S, Amado RG, Chen ISY, Donahue RE . Marking and Gene Expression by a Lentivirus Vector in Transplanted Human and Non-human Primate CD34+Cells.  Journal of Virology. 74:1286-1295. February 2000

An DS; K Morizono; Li Q; Lu, S, Mao S H, Chen ISY.  An inducible HIV-1 vector which effectively suppresses HIV-1 replication. Journal of Virology, 1999 September, 73(9):7671-7677.

Kong LB; An DS; Ackerson B; Canon J; Rey O; Chen ISY; Krogstad P; Stewart PL.  Cryoelectron microscopic examination of human immunodeficiency virus type 1 virions with mutations in the cyclophilin A binding loop. Journal of Virology, 1998 May, 72(5):4403-7. 

An DS; Koyanagi Y; Zhao JQ; Akkina R; Bristol G; Yamamoto N; Zack JA; Chen ISY. High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells. Journal of Virology, 1997 February, 71(2):1397-404.

Hirota M; Koyanagi Y; An DS; Iwanaga Y; Yamamoto N; Shimotohno K. Mutational analysis of the 5' noncoding region of human immunodeficiency virus type1 genome. Leukemia, 1997 April 11 Supplement 3:102-5.