Otto Yang has been on faculty since 1999, and received tenure in 2004. He has a background in clinical infectious diseases, and his laboratory specializes in T cell immunology in HIV infection, relevant to developing immune therapies and vaccines for HIV and potentially other diseases including cancer and other viral infections.
Dr. Yang has a longstanding interest in infectious diseases and HIV-1 pathogenesis. This focus arose from his clinical experience as a medical resident physician at Bellevue Hospital in New York, when >50% of his patients were HIV-1 infected. He then pursued fellowship and postdoctoral training at Massachusetts General Hospital, where he developed a research program studying the role of CD8+ T lymphocytes (CTL, which are killer T cells that can destroy cells infected with viruses or which are malignant) in HIV-1 pathogenesis.
CTL are known to provide important protective immunity for viral infections such as CMV and influenza, and have been identified as a key component of immunity for HIV-1 as well. For this reason, many vaccine efforts have focused on trying to promote anti-HIV-1 CTL responses. However, our basic understanding of how CTL succeed and fail for HIV-1 infection is rudimentary. Dr. Yang's research focus in this area is to explore mechanisms of CTL antiviral function and viral evasion.
His laboratory pursues research on these questions, with projects ranging from controlled in vitro models of CTL-HIV interaction to clinical observational studies. A sampling of ongoing projects includes: studying the factors determining how HIV-1 develops CTL escape mutations (as it does for antiretroviral drugs), the role of the viral Nef protein that renders infected cells resistant to CTL, vaccination strategies for generating HIV-1-specific CTL responses in blood versus mucosa, the premature aging leading to failure of CTL during HIV-1 infection, the immunologic sequelae of perinatal HIV-1 infection, the fitness costs for viral escape mutations against CTL and antiretroviral drugs, the evolution of HIV-1 sequences in different genetic and immune backgrounds, the role of the mucosal immune compartment on susceptibility to HIV-1 infection. The unifying theme of these studies is to understand principles of immunopathogenesis that will be useful for vaccine and immunotherapy development.
A more recent research interest has been the role of CTL in the development of rejection in organ transplant patients. Dr. Yang has begun working with the new composite tissue transplantation program at UCLA, which will perform hand and face transplants, studying the role of this arm of immunity in causing tissue rejection.Finally, he has been working on an exciting new area of nanoparticles called "vaults," which hold promise as a new type of vaccine for HIV and other viruses. In addition to these research interests, Dr. Yang is also a clinician who maintains an active clinical role in the Division of Infectious Diseases.
Publications (of 105 total peer-reviewed papers as of October 2012)
- Anderson DJ, Levine KL, Sang JS, Shah SA, Yang OO, Shank PR, Linial ML. Molecular cloning and characterization of the RNA packaging-defective retrovirus SE21Q1b. J Virology 1992; 66:204-216. PMC238277
- Yang OO, Kalams SA, Rosenzweig M, Trocha A, Jones N, Koziel M, Walker BD, Johnson RP. Efficient lysis of HIV-1 infected cells by cytotoxic T lymphocytes. J Virology 1996; 70:5799-5806. PMC190594
- Yang OO, Kalams SA, Rosenzweig M, Trocha A, Cao H, Luster A, Johnson RP, Walker BD. Suppression of HIV-1 replication by CD8+ cells: Evidence for class I-restricted triggering of cytolytic and noncytolytic mechanisms. J Virology 1997; 71:3120-3128. PMC191444
- Yang OO, Tran-Chen A, Kalams SA, Johnson RP, Roberts MR, Walker BD. Lysis of HIV-1-infected cells and inhibition of viral replication by universal receptor T cells. PNAS 1997; 94:11478-11483. PMC23511
- Wagner L and Yang OO (shared first authorship), Garcia-Zepeda EA, Ge Y, Kalams S, Walker BD, Pasternack MS, Luster AD. Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Nature 1998; 391:908-911. PMID: 9495345
- Shen H, Chen T, Preffer FI, Dombkowski D, Tomasson MH, Golan DE, Yang O, Hofmann W. Sodroski JG, Luster AD, Scadden DT. Intrinsic Human Immunodeficiency Virus type 1 resistance of hematopoietic stem cells despite coreceptor expression. J Virology 1999; 73:728-737. PMC103880
- Yang OO, Swanberg SL, Lu Z, Dziejman M, McCoy J, Luster AD, Walker BD, Herrmann SH. Enhanced inhibition of HIV-1 by Met-SDF-1 beta correlates with down-modulation of CXCR4. J Virology 1999; 73(6):4582-4589. PMC112499
- Brander C, Goulder PJR, Luzuriaga K, Yang OO, Hartman K, Jones NG, Walker BD, Kalams SA. Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in-utero infection. J Immunol 1999; 162:4796-4800. PMID: 10202022
- Brander C, Yang OO, Jones NG, Lee Y, Goulder P, Johnson RP, Trocha A, Colbert D, Hay C, Buchbinder S, Bergmann CC, Zweerink HJ, Wolinsky S, Blattner WA, Kalams SA, Walker BD. Efficient processing of immunodominant HLA-A*0201 restricted HIV-1 cytotoxic T lymphocyte epitope despite multiple variations in the epitope flanking sequences. J Virology 1999; 73:10191-10198. PMC113072
- Severino ME, Sipsas NV, Nguyen PT, Kalam SA, Walker BD, Johnson RP, Yang OO. Inhibition of Human Immunodeficiency Virus Type 1 replication in primary CD4+ T lymphocytes, monocytes, and dendritic cells by cytotoxic T lymphocytes. J Virology 2000; 74: 6695-6699. PMC112184
- Yang OO, Racke FR, Nguyen PT, Gausling R, Severino ME, Horton HF, Byrne MC, Strominger JL, Wilson SB. CD1d on myeloid dendritic cells stimulates cytokine secretion from and cytolytic activity of V alpha24 J alpha Q T cells: a feedback mechanism for immune regulation. J Immunol 2000; 165:3756-3762. PMID: 11034380
- Rusconi S, Merrill DP, La Seta Catamancio S, Citterio P, Bulgheroni E, Croce F, Chou TC, Yang OO, Herrmann SH, Galli M, Hirsch MS. In vitro inhibition of HIV-1 by Met-SDF-1b alone or in combination with antiretroviral drugs. Antiviral Therapy 2000; 5:199-204. PMID: 11075940
- Yang OO, Nguyen PT, Kalams SA, Dorfman T, Gottlinger HG, Stewart S, Chen ISY, Threlkeld S, Walker BD. Nef-mediated resistance of HIV-1 to antiviral CTL. J Virology 2002; 76:1626-1631. PMC135916
- Cole AM, Hong T, Boo LM, Boo LM, Nguyen T, Zhao C, Bristol G, Zack J, Waring AJ, Yang OO, Lehrer RI. Retrocyclin: a primate peptide that protects cells from T- and M-tropic strains of HIV-1. PNAS 2002; 99:1813-1818. PMC122276
- Yang OO, Garcia-Zepeda EA, Walker BD, Luster AD. Monocyte chemoattractant protein-2 inhibits HIV-1 via CCR5. J Infectious Diseases 2002; 185:1174-1178. PMID: 11930329
- Chow YH, Yu D, Zhang JY, Xie YM, Wei OLC, Chiu C. Foroohar M, Yang OO, Park NH, Chen ISY, Pang S. Gp120-independent infection of CD4(-) epithelial cells and CD4(+) T cells by HIV-1. JAIDS 2002; 30:1-8. PMID: 12048357
- Yang OO, Boscardin WJ, Matud J, Hausner MA, Hultin LE, Hultin PM, Shih R, Ferbas J, Siegal FP, Shodell M, Shearer GM, Grene E, Carrington M, O’Brien S, Price CB, Detels R, Jamieson BD, Giorgi JV. Immunologic profile of highly exposed yet HIV-1-seronegative men. AIDS Res Hum Retroviruses 2002; 18:1051-1065. PMID: 12396457
- Gurney KB, Yang OO, Wilson SB, Uittenbogaart CH. TCR gamma delta+ and CD161+ thymocytes express HIV-1 in the SCID-Hu mouse, potentially contributing to immune dysfunction in HIV-1 infection. J Immunol 2002; 169: 5338-5346. PMID: 12391255
- Yang OO. Will we be able to “spot” an effective HIV-1 vaccine? Trends in Immunol 2003; 24: 67-72. PMID: 12547502
- Cole AM, Liao HI, Ganz T, Yang OO. Defensin-like antibacterial activity of peptides derived from envelope glycoproteins of HIV-1. FEBS Letters 2003; 535: 195-199. PMID: 12560103