Young S. Hahn

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Primary Appointment

Professor, Microbiology, Immunology, and Cancer Biology

Education

  • BA, Biochemistry, Yon Sei University, Seoul, Korea
  • PhD, Molecular Biology, California Institute of Technology
  • Postdoc, Immunology, Washington University School of Medicine

Research Disciplines

Biotechnology, Biotechnology, Immunology, Infectious Diseases/Biodefense, Microbiology, Neuroimmunology

Research Interests

Immune regulation for HCV infection and chronic liver inflammation

Research Description

My research is focused on elucidating the immunoregulatory mechanism by Hepatitis C virus (HCV). HCV is a global health concern causing severe liver disease such as fibrosis, cirrhosis and hepatocellular carcinoma. HCV infection in humans is remarkably efficient in establishing viral persistence. T cell responses have been reported to play a pivotal role in controlling HCV infection. However, HCV-specific T cell responses are significantly impaired in chronic HCV patients. This suggests that HCV may employ numerous mechanisms to counteract or possibly suppress the host T cell responses. Recent studies in my lab demonstrate that exosomes released from HCV-infected hepatocytes display TGF-beta at the exosome surface and suppress T cell responses. Exosomes are small membrane-bound extracellular vesicles and serve as natural carriers of signaling molecules to promote cellular crosstalk. We are currently studying to identify the cellular and molecular mechanism for the role of exosomes released from HCV-infected hepatocytes in regulating the host immunity and promoting the development of liver fibrosis. A better understanding of HCV-mediated immune regulation will provide a rational basis for immunotherapeutic strategies to prevent chronic HCV infection and chronic liver diseases.

Personal Statement

Hepatitis C virus (HCV) infection in humans is remarkably efficient in establishing viral persistence, leading to the development of liver cirrhosis and hepatocellular carcinoma. T cell responses have been reported to play a pivotal role in controlling HCV infection.  However, HCV-specific T cell responses are significantly impaired in chronic HCV patients.  This suggests that HCV may employ numerous mechanisms to counteract or possibly suppress the host T cell responses.  Our laboratory is mainly focused on two inter-related arenas of biomedical research to elucidate the mechanism of HCV-mediated inhibition of T cell responses.  Our research program involves both human and mouse studies.  A better understanding of HCV-mediated immune regulation will provide a basis for the rational design of HCV therapeutics.
Interaction of HCV-infected hepatocytes with NK cells and DC.
The primary site of HCV replication occurs within hepatocytes in the liver.  As a result of liver enodothelial cells perforated by fenestrations, hepatocytes are not separated by a basal membrane, and thereby HCV-infected hepatocytes are extensively capable of interacting with innate immune cells including NK, DC.  Recent studies reveal that the function of NK and DC function is significantly impaired in chronic HCV patients.  Given a critical role of NK and DC in limiting HCV replication at the early phase of viral infection, it is likely that HCV-infected hepatocytes might be responsible for impairing NK and DC function by enhancing the expression of immunoregulatory molecules (either soluble or cell surface).  Thus, this impairment of innate immunity attributes to the failure of generating effective T cell responses to clear HCV infection.  In this article, we will review studies highlighting the regulation of innate immunity by HCV and crosstalk between hepatocytes and NK/DC in the hepatic environment.
Alteration of antigen presenting cell function by the binding of extracellular HCV core with the complement receptor.
We have identified HCV core protein as an immunomodulatory molecule capable of suppressing the host immune response and inhibiting viral clearance; and we also determined a host target protein (C1q receptor: gC1qR), which interacts with HCV core. Importantly, HCV core protein is secreted from HCV-infected hepatocytes and free core protein is detectable in the bloodstream of HCV patients.  Our studies revealed that the binding of extracellular HCV core protein to the gC1qR receptor inhibited human T cell responses via its suppressive effect on the activation and induction of pro-inflammatory responses by antigen presenting cells (i.e. macrophages and DC).  This set of crucial observations now provides us with an explanation for why most patients infected with HCV do not clear the infection -- that is, the HCV core protein produced by this virus may play a pivotal role in suppression of host immune response to infection, which allows the virus to establish a persistent infection.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Global Biothreats Training Program
  • Infectious Diseases Training Program
  • Interdisciplinary Training Program in Immunology

Selected Publications

2022

Park, S. -J., & Hahn, Y. S. (2022). Hepatocytes infected with hepatitis C virus change immunological features in the liver microenvironment.. Clinical and molecular hepatology. doi:10.3350/cmh.2022.0032

Jennelle, L. T., Magoro, T., Angelucci, A. R., Dandekar, A., & Hahn, Y. S. (2022). Hepatitis C Virus Alters Macrophage Cholesterol Metabolism Through Interaction with Scavenger Receptors. VIRAL IMMUNOLOGY, 35(3), 223-235. doi:10.1089/vim.2021.0101

Park, S. -J., Nam, D. -E., Seong, H. C., & Hahn, Y. S. (2022). New Discovery of Myeloid-Derived Suppressor Cell's Tale on Viral Infection and COVID-19. FRONTIERS IN IMMUNOLOGY, 13. doi:10.3389/fimmu.2022.842535

2021

Kim, O. -K., Nam, D. -E., & Hahn, Y. S. (2021). The Pannexin 1/Purinergic Receptor P2X4 Pathway Controls the Secretion of MicroRNA-Containing Exosomes by HCV-Infected Hepatocytes. HEPATOLOGY, 74(6), 3409-3426. doi:10.1002/hep.32042

Nam, D. -E., Angelucci, A., Choi, D., Leigh, A., Seong, H. C., & Hahn, Y. S. (2021). Elevation of Plasminogen Activator Inhibitor-1 Promotes Differentiation of Cancer Stem-Like Cell State by Hepatitis C Virus Infection. JOURNAL OF VIROLOGY, 95(10). doi:10.1128/JVI.02057-20

Nam, D. -E., Seong, H. C., & Hahn, Y. S. (2021). Plasminogen Activator Inhibitor-1 and Oncogenesis in the Liver Disease.. Journal of cellular signaling, 2(3), 221-227. doi:10.33696/signaling.2.054

2020

Bak, M., Park, J., Min, K., Cho, J., Seong, J., Hahn, Y. S., . . . Kwon, I. (2020). Recombinant Peptide Production Platform Coupled with Site-Specific Albumin Conjugation Enables a Convenient Production of Long-Acting Therapeutic Peptide. PHARMACEUTICS, 12(4). doi:10.3390/pharmaceutics12040364

2019

Magoro, T., Dandekar, A., Jennelle, L. T., Bajaj, R., Lipkowitz, G., Angelucci, A. R., . . . Hahn, Y. S. (2019). IL-1 beta/TNF-alpha/IL-6 inflammatory cytokines promote STAT1-dependent induction of CH25H in Zika virus-infected human macrophages. JOURNAL OF BIOLOGICAL CHEMISTRY, 294(40), 14591-14602. doi:10.1074/jbc.RA119.007555

Cobb, D. A., Dandekar, A. P., & Hahn, Y. S. (2019). Detection of Antigen-Specific CD8(+) T Cells in the Livers of HCV Core Transgenic Mice. HEPATITIS C VIRUS PROTOCOLS, 1911, 453-458. doi:10.1007/978-1-4939-8976-8_31

2018

Dolina, J. S., Cechova, S., Rudy, C. K., Sung, S. -S. J., Tang, W. W., Lee, J., . . . Le, T. H. (2018). Correction: Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression.. Journal of immunology (Baltimore, Md. : 1950), 201(8), 2521. doi:10.4049/jimmunol.1801186

Cobb, D. A., Kim, O. -K., Golden-Mason, L., Rosen, H. R., & Hahn, Y. S. (2018). Hepatocyte-derived exosomes promote T follicular regulatory cell expansion during hepatitis C virus infection. HEPATOLOGY, 67(1), 71-85. doi:10.1002/hep.29409

2017

Cho, J., Lim, S. I., Yang, B. S., Hahn, Y. S., & Kwon, I. (2017). Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation. SCIENTIFIC REPORTS, 7. doi:10.1038/s41598-017-18029-y

Sung, S. -S. J., Ge, Y., Dai, C., Wang, H., Fu, S. M., Sharma, R., . . . Lawler, J. R. (2017). Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow-Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice. JOURNAL OF IMMUNOLOGY, 198(7), 2589-2601. doi:10.4049/jimmunol.1601565

Tosello-Trampont, A., Surette, F. A., Ewald, S. E., & Hahn, Y. S. (2017). Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration. FRONTIERS IN IMMUNOLOGY, 8. doi:10.3389/fimmu.2017.00301

Dolina, J. S., Cechova, S., Rudy, C. K., Sung, S. -S. J., Tang, W. W., Lee, J., . . . Le, T. H. (2017). Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression. JOURNAL OF IMMUNOLOGY, 198(6), 2341-2351. doi:10.4049/jimmunol.1502234

Labonte, A. C., Sung, S. -S. J., Jennelle, L. T., Dandekar, A. P., & Hahn, Y. S. (2017). Expression of Scavenger Receptor-AI Promotes Alternative Activation of Murine Macrophages to Limit Hepatic Inflammation and Fibrosis. HEPATOLOGY, 65(1), 32-43. doi:10.1002/hep.28873

Krueger, P. D., Narayanan, S., Surette, F. A., Brown, M. G., Sung, S. -S. J., & Hahn, Y. S. (2017). Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8(+) T cells. JOURNAL OF LEUKOCYTE BIOLOGY, 101(1), 329-338. doi:10.1189/jlb.3A0516-225R

2016

Narayanan, S., Nieh, A. H., Kenwood, B. M., Davis, C. A., Tosello-Trampont, A. -C., Elich, T. D., . . . Hahn, Y. S. (2016). Distinct Roles for Intracellular and Extracellular Lipids in Hepatitis C Virus Infection. PLOS ONE, 11(6). doi:10.1371/journal.pone.0156996

Narayanan, S., Surette, F. A., & Hahn, Y. S. (2016). The Immune Landscape in Nonalcoholic Steatohepatitis. IMMUNE NETWORK, 16(3), 147-158. doi:10.4110/in.2016.16.3.147

Goh, C. C., Roggerson, K. M., Lee, H. -C., Golden-Mason, L., Rosen, H. R., & Hahn, Y. S. (2016). Hepatitis C Virus-Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN-gamma Production by Altering Cellular Metabolism via Arginase-1. JOURNAL OF IMMUNOLOGY, 196(5), 2283-2292. doi:10.4049/jimmunol.1501881

Tosello-Trampont, A. -C., Krueger, P., Narayanan, S., Landes, S. G., Leitinger, N., & Hahn, Y. S. (2016). NKp46(+) Natural Killer Cells Attenuate Metabolism-Induced Hepatic Fibrosis by Regulating Macrophage Activation in Mice. HEPATOLOGY, 63(3), 799-812. doi:10.1002/hep.28389

Jennelle, L. T., Dandekar, A. P., Magoro, T., & Hahn, Y. S. (2016). Immunometabolic Signaling Pathways Contribute to Macrophage and Dendritic Cell Function. CRITICAL REVIEWS IN IMMUNOLOGY, 36(5), 379-394. doi:10.1615/CritRevImmunol.2017018803

2015

Lim, S. I., Hahn, Y. S., & Kwon, I. (2015). Site-specific albumination of a therapeutic protein with multi-subunit to prolong activity in vivo. JOURNAL OF CONTROLLED RELEASE, 207, 93-100. doi:10.1016/j.jconrel.2015.04.004

Krueger, P. D., Kim, T. S., Sung, S. -S. J., Braciale, T. J., & Hahn, Y. S. (2015). Liver-Resident CD103(+) Dendritic Cells Prime Antiviral CD8(+) T Cells In Situ. JOURNAL OF IMMUNOLOGY, 194(7), 3213-3222. doi:10.4049/jimmunol.1402622

2014

Ely, K. H., Matsuoka, M., DeBerge, M. P., Ruby, J. A., Liu, J., Schneider, M. J., . . . Enelow, R. I. (2014). Tissue-Protective Effects of NKG2A in Immune-Mediated Clearance of Virus Infection. PLOS ONE, 9(9). doi:10.1371/journal.pone.0108385

Golden-Mason, L., Hahn, Y. S., Strong, M., Cheng, L., & Rosen, H. R. (2014). Extracellular HCV-Core Protein Induces an Immature Regulatory Phenotype in NK Cells: Implications for Outcome of Acute Infection. PLOS ONE, 9(7). doi:10.1371/journal.pone.0103219

Labonte, A. C., Tosello-Trampont, A. -C., & Hahn, Y. S. (2014). The Role of Macrophage Polarization in Infectious and Inflammatory Diseases. MOLECULES AND CELLS, 37(4), 275-285. doi:10.14348/molcells.2014.2374

Dolina, J. S., Braciale, T. J., & Hahn, Y. S. (2014). Liver-Primed CD8(+) T Cells Suppress Antiviral Adaptive Immunity Through Galectin-9-Independent T-Cell Immunoglobulin and Mucin 3 Engagement of High-Mobility Group Box 1 in Mice. HEPATOLOGY, 59(4), 1351-1365. doi:10.1002/hep.26938

Lee, H. -C., Narayanan, S., Park, S. -J., Seong, S. -Y., & Hahn, Y. S. (2014). Transcriptional Regulation of IFN- lambda Genes in Hepatitis C Virus- infected Hepatocytes via IRF-3IRF-7NF-kappa B Complex*. JOURNAL OF BIOLOGICAL CHEMISTRY, 289(8), 5310-5319. doi:10.1074/jbc.M113.536102

2013

Lim, S. I., Mizuta, Y., Takasu, A., Hahn, Y. S., Kim, Y. H., & Kwon, I. (2013). Site-specific fatty acid-conjugation to prolong protein half-life in vivo. JOURNAL OF CONTROLLED RELEASE, 170(2), 219-225. doi:10.1016/j.jconrel.2013.05.023

Goh, C., Narayanan, S., & Hahn, Y. S. (2013). Myeloid-derived suppressor cells: the dark knight or the joker in viral infections?. IMMUNOLOGICAL REVIEWS, 255(1), 210-221. doi:10.1111/imr.12084

Braciale, T. J., & Hahn, Y. S. (2013). Immunity to viruses. IMMUNOLOGICAL REVIEWS, 255(1), 5-12. doi:10.1111/imr.12109

Gorski, S. A., Hahn, Y. S., & Braciale, T. J. (2013). Group 2 Innate Lymphoid Cell Production of IL-5 Is Regulated by NKT Cells during Influenza Virus Infection. PLOS PATHOGENS, 9(9). doi:10.1371/journal.ppat.1003615

Caldwell, S., Hoehn, K. L., & Hahn, Y. S. (2013). The Strange and Critical Intersection of Hepatitis C and Lipoprotein Metabolism: "C-zing" the Oil. HEPATOLOGY, 57(5), 1684-1687. doi:10.1002/hep.26091

Lee, H. -C., Sung, S. -S. J., Krueger, P. D., Jo, Y. -A., Rosen, H. R., Ziegler, S. F., & Hahn, Y. S. (2013). Hepatitis C virus promotes t-helper (Th)17 responses through thymic stromal lymphopoietin production by infected hepatocytes. HEPATOLOGY, 57(4), 1314-1324. doi:10.1002/hep.26128

Dolina, J. S., Sung, S. -S. J., Novobrantseva, T. I., Nguyen, T. M., & Hahn, Y. S. (2013). Lipidoid Nanoparticles Containing PD-L1 siRNA Delivered In Vivo Enter Kupffer Cells and Enhance NK and CD8(+) T Cell-mediated Hepatic Antiviral Immunity. MOLECULAR THERAPY-NUCLEIC ACIDS, 2. doi:10.1038/mtna.2012.63

Dolina, J. S., Sung, S. J., Novobrantseva, T. I., Nguyen, T. M., & Hahn, Y. S. (2013). Lipidoid Nanoparticles Containing PD-L1 siRNA Delivered In Vivo Enter Kupffer Cells and Enhance NK and CD8(+) T Cell-mediated Hepatic Antiviral Immunity.. Mol Ther Nucleic Acids, 2, e72. doi:10.1038/mtna.2012.63

2012

Tosello-Trampont, A. -C., Landes, S. G., Nguyen, V., Novobrantseva, T. I., & Hahn, Y. S. (2012). Kuppfer Cells Trigger Nonalcoholic Steatohepatitis Development in Diet-induced Mouse Model through Tumor Necrosis Factor-alpha Production. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(48), 40161-40172. doi:10.1074/jbc.M112.417014

Tacke, R. S., Lee, H. -C., Goh, C., Courtney, J., Polyak, S. J., Rosen, H. R., & Hahn, Y. S. (2012). Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. HEPATOLOGY, 55(2), 343-353. doi:10.1002/hep.24700

2011

Tacke, R. S., Tosello-Trampont, A., Nguyen, V., Mullins, D. W., & Hahn, Y. S. (2011). Extracellular Hepatitis C Virus Core Protein Activates STAT3 in Human Monocytes/Macrophages/Dendritic Cells via an IL-6 Autocrine Pathway. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(12), 10847-10855. doi:10.1074/jbc.M110.217653

Krueger, P. D., Lassen, M. G., Qiao, H., & Hahn, Y. S. (2011). Regulation of NK Cell Repertoire and Function in the Liver. CRITICAL REVIEWS IN IMMUNOLOGY, 31(1), 43-52. doi:10.1615/CritRevImmunol.v31.i1.40

2010

Hall, C. H. T., Kassel, R., Tacke, R. S., & Hahn, Y. S. (2010). HCV+ Hepatocytes Induce Human Regulatory CD4(+) T Cells through the Production of TGF-beta. PLOS ONE, 5(8). doi:10.1371/journal.pone.0012154

Park, S. -J., & Hahn, Y. S. (2010). Regulation of host innate immunity by hepatitis C virus: crosstalk between hepatocyte and NK/DC.. Reviews in infection, 1(3), 151-157.

Tang, X., Wagoner, J., Negash, A., Austin, M., McLauchlan, J., Hahn, Y. S., . . . Polyak, S. J. (2010). Functional Characterization of Core Genes from Patients with Acute Hepatitis C Virus Infection. JOURNAL OF INFECTIOUS DISEASES, 201(6), 912-922. doi:10.1086/650699

Lassen, M. G., Lukens, J. R., Dolina, J. S., Brown, M. G., & Hahn, Y. S. (2010). Intrahepatic IL-10 Maintains NKG2A(+)Ly49(-) Liver NK Cells in a Functionally Hyporesponsive State. JOURNAL OF IMMUNOLOGY, 184(5), 2693-2701. doi:10.4049/jimmunol.0901362