Dr. Seung-Hwan Lee

Biography

Are you interested in joining the Lee Lab for your graduate or postdoctoral training? Please send your CV to [email protected]

Research Overview

My lab focuses on critical questions involving natural killer (NK) cells with two major research themes: (1) Identification of novel NK cell functions and dissection of mechanisms for those functions in vivo in models of infection and cancer; (2) Application of these new findings for developing innovative therapeutics. We have established a network of collaborations with clinical investigators in order to elucidate new NK cell functions of relevance to cancer therapy and treatment of chronic infections.

1. HOW NK CELLS ARE GENERATED:

Understanding the mechanism leading to NK cell maturation at the steady-state. The networks of transcription factors and cytokine signaling during NK cell development are being investigated.

2. HOW NK CELLS METABOLIZE NUTRIENTS:

Natural Killer Cell Immunometabolism. The metabolic reprogramming in immune cells required for proliferation is controlled by signaling from antigen-specific receptors and growth factor cytokines, as well as the accessibility of nutrients. We are investigating the cytokine signaling that is modulating NK cell and CD8 T cell metabolism during virus infection and inflammation.

3. HOW NK CELL FUNCTIONS DURING VIRAL INFECTIONS:

Through collaborations with clinical investigators, we have access to clinical samples from HCV, HIV, CMV, and Influenza infected individuals. We are investigating NK cell function in human viral infection by evaluating the cytokine production and the cytotoxicity of NK cells from clinical specimens.

4. HOW TO IMPROVE NK CELL FUNCTIONS IN IMMUNOTHERAPIES:

Therapeutic monoclonal antibodies (mAbs) that recognize tumor-specific antigens on the surface of tumor cells are being used successfully as cancer therapy. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a principal mechanism underlying the therapy. We are trying to enhance the ADCC function of NK cells and thereby improve the efficacy of the immunotherapies.

PUBLICATIONS

• Sara El-Sahli, Khang Hua, Andrew Sulaiman, Li Li, Elijah Farah, Dan Liu, Jason Chambersa, Sarah McGarry, Peiyong Zheng, Seung-Hwan Lee, Jiefeng Cui, Marc Ekker, Marceline Cote, Tommy Alain, Lisheng Wang, and Suresh Gadde. A triple-drug nanotherapy to target breast cancer cells, cancer stem cells and tumor vasculature. ChemComm, Submitted, 2019.
• Alaa Kassim Ali, Amandeep Kaur Komal, Saeedah Musaed Almutairi, Axel Roers, Eric Vivier, and Seung-Hwan Lee. Natural killer cell-derived IL-10 regulates T cell response to prevent liver damage during sustained murine cytomegalovirus infection. Frontier in Immunology, DOI: 10.3389/fimmu.2019.02688, 2019.
• Tri Dinh, Jun Oh, Donald William Cameron, Seung-Hwan Lee*, and Juthaporn Cowan*. Differential immunomodulation of T-cells by immunoglobulin replacement therapy in primary and secondary antibody deficiency. *Co-corresponding authors. PLOS One, DOI: 10.1371/journal.pone.0223861, 2019.
• Andrew Sulaiman, Sarah McGarry, Sara El-Sahli, Li Li, Jason Chambers, Alexandra Phan, Marceline Cote, Greg O Cron, Tommy Alain, Yevgeniya Le, Seung-Hwan Lee, Sheng Liu, Daniel Figeys, Suresh Gadde, and Lisheng Wang. Co-Targeting Bulk Tumor and CSCs in Clinically Translatable TNBC Patient-Derived Xenografts via Combination Nanotherapy, Molecular Cancer Therapeutics, DOI: 10.1158/1535-7163, 2019.
• SoonHo Kweon1, Minh-Trang Thi Phan, Sejong Chun, HongBi Yu, Jinho Kim, Seokho Kim, Jaemin Lee, Alaa Kassim Ali, Seung-Hwan Lee, Sang-Ki Kim, Junsang Doh and Duck Cho. Expansion of Human NK Cells Using K562 Cells Expressing OX40 Ligand and Short Exposure to IL-21, Frontier in Immunology, DOI.10.3389/fimmu.2019.
• Saeedah Musaed Almutairi*, Alaa Kassim Ali*, William He, Doo-Seok Yang, Peyman Ghorbani, Lisheng Wang, Morgan D. Fullerton, and Seung-Hwan Lee. Interleukin-18 up-regulates amino acid transporters and facilitates amino acid–induced mTORC1 activation in natural killer cells. *Equal contribution. Journal of Biological Chemistry, 294, 4644-4655, 2019.
• Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, and Duck Cho. Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population: Reference range, influence of age and sex, and correlation between NK cell receptors and cytotoxicity. Human Immunology. 78, 103-112, 2017.
• Mir Munir A. Rahim, Andrew Wight, Ahmad Bakur Mahmoud, Oscar A. Aguilar, Seung-Hwan Lee, Silvia M. Vidal, James R. Carlyle, Andrew P. Makrigiannis. Expansion and protection by a virus-specific NK cell subset lacking the expression of inhibitory NKR-P1B receptor during murine cytomegalovirus infection.  Journal of Immunology 197, 2325-2337, 2016.Ahmad Bakur Mahmoud, Megan M. Tu, Haggag S. Zein, Mir Munir A. Rahim, Andrew Wight, Seung-Hwan Lee, Harman S. Sekhon, Earl G. Brown, Andrew P. Makrigiannis. Influenza virus targets class I MHC-educated NK cells for immunoevasion. PLoS Pathog. 12(2):e1005446, 2016.
• Alaa Kassim Ali, Jun Seok Oh, Eric Vivier, Meinrad Busslinger and Seung-Hwan Lee. Natural killer cell-specific Gata3 ablation identifies the maturation program required for bone marrow exit and control of proliferation. Journal of Immunology 196, 1753-1767, 2016.
• Jun Seok Oh, Alaa Kassim Ali, Sungjin Kim, Daniel J. Corsi, Curtis Cooper and Seung-Hwan Lee. NK cells lacking FcεRIγ is associated with reduced liver damage in chronic hepatitis C virus infection. Eur J Immunol. 46, 1020-1029, 2016.
• Alaa Kassim Ali, Neethi Nandagopal, and Seung-Hwan Lee.  IL-15-PI3K-AKT-mTOR: The pathway taking care of life journey of Natural Killer cells. Frontiers in Immunology 6:355. doi: 10.3389/fimmu.2015.00355, 2015.
• HeeJo Baek, Da-Woon Kim, Minh-Trang Thi Phan, Ju-Sun Kim, Jihoon Yang, Jeong-il Choi, JeJung Lee, Myung-Geung Shin, Dong-Wook Ryang, Sang-Ki Kim, Seung-Hwan Lee, Hoon Kook, Duck Cho. Comparison of FcR-deficient natural killer cells between cord and adult blood in the cytomegalovirus-endemic Korean population. Annals of Laboratory Medicine, 35, 423-428, 2015.
• Neethi Nandagopal, Alaa Ali, Amandeep Komal and Seung-Hwan Lee. The Critical Role of IL-15-PI3K-mTOR Pathway in Natural Killer Cell Effector Functions. Frontiers in Immunology 5:187. doi: 10.3389/fimmu.2014.00187. 2014.
• Margarite L. Tarrio*, Seung-Hwan Lee*, Maria F. Fragoso, Hong-Wei Sun, Yuka Kanno, John J. O’Shea, and Christine A. Biron. Proliferation Conditions Promote Intrinsic Changes in NK Cells for an IL-10 Response. Journal of Immunology 193, 354-363, 2014. *Equal contribution.
• Dong-Pyo Lim, Youn-Young Jang, Seokho Kim, Sang Seok Koh, Je-Jung Lee, Ju-Sun Kim, Minh-Trang Thi Phan, Dong-Jun Shin, Myung-Geun Shin, Seung-Hwan Lee, Meesun Yoon, Sang-Ki Kim, Jung-Han Yoon, Min-Ho Park, Duck Cho. Effect of exposure to IL-21 at various time points on the ex vivo expansion of human natural killer cells. Cytotherapy 14, S1465-3249, 2014.
• Seung-Hwan Lee*, Maria F. Fragoso*, and Christine A. Biron. Cutting Edge: A Novel Mechanism Bridging Innate and Adaptive Immunity: IL-12 Induction of CD25 To Form High-Affinity IL-2 Receptors on NK Cells. Journal of Immunology 189, 2712-2716, 2012. *Equal contribution. 
• M. Pilar Gil, Mickaël J. Y. Ploquin, Wendy T. Watford, Seung-Hwan Lee, Kwangsin Kim, Xin Wang, Yuka Kanno, John J. O’Shea, and Christine A. Biron. Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function. Blood, 120, 3718-3728, 2012.
• Seung-Hwan Lee, and Christine A. Biron. Here Today – Not Gone Tomorrow:  Roles for Activating Receptors in Sustaining NK Cells for Function During Viral Infections. European Journal of Immunology 40, 923-932, 2010. 
• Seung-Hwan Lee, Kwang-Sin Kim, Nassima Fodil-Cornu, Silvia M. Vidal, and Christine A. Biron. Activating receptors promote NK cell expansion for maintenance, IL-10 production, and CD8 T cell regulation during viral infection. The Journal of Experimental Medicine 206, 2235-2251, 2009 (Highlighted in Nature Immunology Reviews).
• Nassima Fodil-Cornu, Seung-Hwan Lee, Simon Belanger, Andrew P. Makrigiannis, Christine A. Biron, R. Mark Buller and Silvia M. Vidal. Ly49h deficient C57BL/6 mice: a new MCMV susceptible model remains resistant to unrelated pathogens controlled by the Natural Killer gene Complex. Journal of Immunology 181, 6394-6405, 2008.
• Seung-Hwan Lee, Takuya Miyagi, and Christine A. Biron. Keeping NK cells in highly regulated antiviral warfare. Trends in Immunology, 28, 252-259, 2007 (Featured in Issue cover).
• Seung-Hwan Lee, Ken Dimock, Douglas A Gray, Nicole Beauchemin, Kathryn V. Holmes, Majid Belouchi, John Realson, Silvia M. Vidal. Maneuvering for advantage: the genetics of mouse susceptibility to virus infection. Trends in Genetics. 8, 447-457, 2003.
• Zoha Kibar, Susan Gauthier, Seung-Hwan Lee, Silvia Vidal and Philippe Gros. Rescue of the neural tube defect of loop-tail mice by a BAC clone containing the Ltap gene. Genomics 82, 397-400, 2003.
• Seung-Hwan Lee, Ahmed Zafer, Yves de Repentigny, Rashmi Kothary, Michel L. Tremblay, Philippe Gros, Pascale Duplay, John R. Webb and Silvia M. Vidal. Transgenic expression of the activating natural killer receptor Ly49H confers resistance to cytomegalovirus infection in genetically susceptible mice. The Journal of Experimental Medicine 197, 515-526, 2003.
• Eduardo Diez, Seung-Hwan Lee, Susan Gauthier, Silvia M. Vidal and Philippe Gros. Birc1e (Naip5) is the Legionella pneumophila resistance locus Lgn1. Nature Genetics 33, 55-60, 2003.
• Seung-Hwan Lee, John R. Webb, Silvia M. Vidal. Innate immunity to cytomegalovirus: the Cmv1 locus and its role in natural killer cell function. Microbes and infection 4, 1491-1503, 2002.
• Seung-Hwan Lee, Silvia M. Vidal. Functional diversity of Mx proteins: variations on a theme of host resistance to infection. Genome Research 12, 527-530, 2002.
• John R. Webb, Seung-Hwan Lee and Silvia M. Vidal. Genetic control of innate immune responses against cytomegalovirus: MCMV meets its match.  Genes and Immunity 3, 250-262, 2002.
• Seung-Hwan Lee, Sonia Girard, Denis Macina, Maria Busa, Ahmed Zafer, Abdelmajid Belouchi, Philippe Gros and Silvia M. Vidal. Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily. Nature Genetics 28, 42-45, 2001 (Highlighted in News and Views).
• Seung-Hwan Lee, John Gitas, Ahmed Zafer, Pierre Lepage, Tom Hudson, Abdelmajid Belouchi and Silvia M. Vidal. Haplotype mapping indicates two independent origins for the Cmv1s susceptibility allele to cytomegalovirus infection and refines its localization within the Ly49 cluster. Immunogenetics 53, 501-505, 2001.
• Seung-Hwan Lee, John A. Davison, Silvia M. Vidal and Abdelmajid Belouchi. Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.  Mammalian Genome 12, 157-162, 2001.
• Chantal Depatie, Seung-Hwan Lee, Amanda Stafford, Philippe Avener, Philippe Gros and Silvia M. Vidal. Long-range physical map, transcription map and construction of a sequence-ready BAC contig of a 2-Mb region overlapping the host resistance locus Cmv1 on distal mouse chromosome 6. Genomics 66, 161-174, 2000.
• Chantal Depatie, Anick Chalifour, Catherine Pare, Seung-Hwan Lee, Silvia M. Vidal and Suzanne Lemieux. Assessment of Cmv1 candidates by genetic mapping and in vivo antibody depletion of NK cell subsets. International Immunology 11, 1541-1551, 1999.
• Jong-Seok Lim, Seung-Hwan Lee, Eunsik Lee, Young Kang, Jae Wha Kim and Yong-Kyung Choe. Differential expression of ferritin heavy chain in THP-1 cells infected with Mycobacterium Bovis BCG. Biochemistry and Molecular Biology International 43, 981-988, 1997. 
• Mi Young Han, Mi Young Son, Seung-Hwan Lee, Jin Koo Kim and Yong-Kyung Choe. Molecular cloning of the LeuB genes from Mycobacterium Bovis BCG and Mycobacterium Tuberculosis. Biochemistry and Molecular Biology International 41, 657-663, 1997.
• Dong-Whan Lee, Seung-Hwan Lee, Hyun-A Hwang, J.H. Kim and Keon-Sang Chae. Quantitative analysis of gene expression in sexual structures of Aspergillus nidulans by sequencing of 3’-directed cDNA clones. FEMS Microbiology Letters 138, 71-76, 1996.

Referred Chapters in books

• Minh-Trang Thi Phan, Seung-Hwan Lee, Sang-Ki Kim and Duck Cho. Expansion of NK cells using genetically engineered K562 feeder cells. Natural Killer Cells: Methods in Molecular Biology 1441, Srinivas S. Somanchi, ed. Humana Press, Inc., 167-74, 2016.
• Takuya Miyagi, Seung-Hwan Lee, and Christine A. Biron. Intracellular staining for analysis of the expression and phosphorylation of signal transducers and activators of transcription (STATs) in NK cells. In: Second Edition of NK Cell Protocols, Methods in Molecular Biology 612, K.S. Campbell, ed. Humana Press, Inc., 159-175, 2010.