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Date: 13 May 2025 (Tue)
Time: 11am - 12:30pm (SGT) Format: Virtual (Zoom Meeting) Host: Albert W. CHENG, Institute of Zoology, Chinese Academy of Sciences, China Co-host: Heeju RYU, Sungkyunkwan University, South Korea |
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Speaker's information
Haoyi WANG Institute of Zoology, Chinese Academy of Sciences, China "Improving T Cell therapy using novel gene editing tools" Pubmed |
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ABSTRACT
Gene editing technologies represented by CRISPR/Cas have revolutionized biology. But the relatively large size of existing tools makes them difficult to deliver, thus limiting their application. In addition, existing technologies are still inefficient in integrating large DNA fragment in some species and cell types. Therefore, we have focused on the development of novel gene editing tools with small size or the ability to integrate large fragments of DNA. Using an evolutionary genomics approach, we systematically studied the TnpB protein of the IS605 family of prokaryotic transposons and DNA transposons in 102 eukaryotic genomes, and identified multiple TnpB systems with high activity and DNA transposon tools with gene integration activity in human cells. These findings enrich the genetic engineering toolbox and provide functional data and understanding for the study of transposon biology.
BIO
Haoyi Wang, Ph.D., is a Principal Investigator at the Institute of Zoology, Chinese Academy of Sciences (CAS). For many years, he has been engaged in the development and application of genetic engineering technologies. His work includes the development of novel TnpB and Argonaute-targeted nucleases for gene editing, the discovery of new DNA transposon tools, and the identification of tandem repeat-based DNA-binding proteins.He has established efficient gene-editing methods in human pluripotent stem cells and T cells, and has engineered gene-editing-enhanced CAR-T cells. To date, he has published over 70 SCI-indexed papers, with key findings published as corresponding or co-corresponding author in top-tier journals such as Cell, Nature Biotechnology, Cancer Cell, and Cell Stem Cell.
Gene editing technologies represented by CRISPR/Cas have revolutionized biology. But the relatively large size of existing tools makes them difficult to deliver, thus limiting their application. In addition, existing technologies are still inefficient in integrating large DNA fragment in some species and cell types. Therefore, we have focused on the development of novel gene editing tools with small size or the ability to integrate large fragments of DNA. Using an evolutionary genomics approach, we systematically studied the TnpB protein of the IS605 family of prokaryotic transposons and DNA transposons in 102 eukaryotic genomes, and identified multiple TnpB systems with high activity and DNA transposon tools with gene integration activity in human cells. These findings enrich the genetic engineering toolbox and provide functional data and understanding for the study of transposon biology.
BIO
Haoyi Wang, Ph.D., is a Principal Investigator at the Institute of Zoology, Chinese Academy of Sciences (CAS). For many years, he has been engaged in the development and application of genetic engineering technologies. His work includes the development of novel TnpB and Argonaute-targeted nucleases for gene editing, the discovery of new DNA transposon tools, and the identification of tandem repeat-based DNA-binding proteins.He has established efficient gene-editing methods in human pluripotent stem cells and T cells, and has engineered gene-editing-enhanced CAR-T cells. To date, he has published over 70 SCI-indexed papers, with key findings published as corresponding or co-corresponding author in top-tier journals such as Cell, Nature Biotechnology, Cancer Cell, and Cell Stem Cell.
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Hyungseok SEO
Seoul National University, Republic of Korea "Reinvigorating CAR T cells: transcriptional and epigenetic modulation to overcome exhaustion in solid tumors" Pubmed |
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ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in treating hematological malignancies but remains less effective against solid tumors due to T cell exhaustion—a dysfunctional state driven by chronic antigen exposure and the tumor microenvironment. Key transcription factors such as NR4A family members (Nr4a1/2/3), TOX/TOX2, and epigenetic modulators like TET enzymes contribute to this hyporesponsiveness by promoting inhibitory receptor expression and suppressing effector function. Recent studies reveal that disrupting NR4A and TOX pathways enhances CAR T cell cytokine production and cytotoxicity, leading to improved tumor clearance. Furthermore, overexpression of BATF and its cooperation with IRF4 can counteract exhaustion by promoting memory formation and effector persistence. Combining TET enzyme knockout with IL-21 signaling further supports CAR T cell survival and expansion. These findings suggest that targeting transcriptional and epigenetic regulators offers a promising strategy to optimize CAR T cell function in solid tumor immunotherapy.
BIO
Hyungseok Seo is an Assistant Professor at the College of Pharmacy, Seoul National University, where he leads the Seo Lab for Cell & Gene Therapy. His research focuses on cancer immunotherapy and engineered immune cells, with an emphasis on T cell exhaustion and cytokine regulation. Prior to his current position, he served as Principal Scientist and Project Leader at Novartis Institutes for BioMedical Research in Cambridge, MA. He completed postdoctoral training at the La Jolla Institute for Immunology and earned his Ph.D. in Immunology from Seoul National University. Dr. Seo has received numerous honors, including the CRI-Irvington and AACR-Genentech fellowships, and multiple awards from the American Association of Immunologists and Korean scientific societies. He has published in top-tier journals such as Nature, Nature Immunology, and PNAS, and holds several patents in the field of immune engineering, underlining his impact on advancing translational immunotherapy.
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in treating hematological malignancies but remains less effective against solid tumors due to T cell exhaustion—a dysfunctional state driven by chronic antigen exposure and the tumor microenvironment. Key transcription factors such as NR4A family members (Nr4a1/2/3), TOX/TOX2, and epigenetic modulators like TET enzymes contribute to this hyporesponsiveness by promoting inhibitory receptor expression and suppressing effector function. Recent studies reveal that disrupting NR4A and TOX pathways enhances CAR T cell cytokine production and cytotoxicity, leading to improved tumor clearance. Furthermore, overexpression of BATF and its cooperation with IRF4 can counteract exhaustion by promoting memory formation and effector persistence. Combining TET enzyme knockout with IL-21 signaling further supports CAR T cell survival and expansion. These findings suggest that targeting transcriptional and epigenetic regulators offers a promising strategy to optimize CAR T cell function in solid tumor immunotherapy.
BIO
Hyungseok Seo is an Assistant Professor at the College of Pharmacy, Seoul National University, where he leads the Seo Lab for Cell & Gene Therapy. His research focuses on cancer immunotherapy and engineered immune cells, with an emphasis on T cell exhaustion and cytokine regulation. Prior to his current position, he served as Principal Scientist and Project Leader at Novartis Institutes for BioMedical Research in Cambridge, MA. He completed postdoctoral training at the La Jolla Institute for Immunology and earned his Ph.D. in Immunology from Seoul National University. Dr. Seo has received numerous honors, including the CRI-Irvington and AACR-Genentech fellowships, and multiple awards from the American Association of Immunologists and Korean scientific societies. He has published in top-tier journals such as Nature, Nature Immunology, and PNAS, and holds several patents in the field of immune engineering, underlining his impact on advancing translational immunotherapy.