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Research Overview

The primary focus of my research group is to investigate HIV-1 pathogenesis and stem cell and T-cell biology in antiviral and cell therapy settings. We develop genomics tools and animal study models to understand blood cell functions at the individual cell and individual virus levels (Science Advances 2020; PLoS Computational Biology, 2018, BMC Biology, 2015; Cell Stem Cell 2014) and to improve the safety and efficacy of cell and gene therapies (Frontiers in Immunology 2022; Biomedicines 2022; Cell reports 2022). Our cell-tracking and virus-tracking studies have revealed tremendous diversities of individual stem cells and mature T cells that have not been seen in conventional population-based studies.

 

1. Systems-level analysis of polyclonal hematopoietic repopulation

Retroviral tagging (cellular barcoding) has proven useful in evaluating HSC and T-cell transplant and the effects of genetic modification on cellular behaviors in vivo. We develop and utilize high-throughput and quantitative stem cell tracking assay. We have demonstrated a complex yet well-orchestrated repopulation by thousands of HSC clones in nonhuman primates and competitive repopulation of anti-HIV and control engineered HSCs in humanized mice.

  • 1a.  Sanggu Kim, Namshin Kim, Angela P. Presson, Mark E. Metzger, Aylin C. Bonifacino, Mary Sehl, Samson A. Chow, Gay M. Crooks, Cynthia E. Dunbar, Dong Sung An, Robert E. Donahue and Irvin S.Y. Chen, “Dynamics of HSPC Repopulation in Non-human Primates Revealed by a Decade-long Clonal-Tracking Study”, 2014, Cell Stem Cell, 14 (4), p419–420. PMID:24702996; PMCID:PMC4009343
  • 1b.  Sidhartha Goyal*, Sanggu Kim*, Irvin SY Chen and Tom Chou, “Mechanisms of blood homeostasis: lineage tracking and a neutral model of cell populations in rhesus macaque”, 2015, BMC Biology, 20;13:85, PMCID: PMC4615871. *equal contribution
  • 1c.  Gajendra W. Suryawanshi; Wannisa Khamaikawin; Jing Wen; Saki Shimizu; Hubert Arokium; Yiming Xie; Eugene Wang; Shihyoung Kim; Hyewon Choi; Chong Zhang; Angela P. Presson; Namshin Kim; Dong-Sung An; Irvin S. Y. Chen; Sanggu Kim, “The clonal repopulation of HSPC gene-modified with anti-HIV-1 RNAi is not impacted by pre-existing HIV-1 infection”, Science Advances (IF:13.116), 22 Jul 2020: Vol. 6, no. 30, eaay9206; PMID: 32766447 Senior corresponding author

 

2. Understanding T-cell dynamics following systemic perturbation in vivo

Based on our long-term clonal repopulation data, we investigate how hematopoietic clonal repopulation changes by systemic and transient T-cell depletion by CD3-immunotoxin and demonstrated skewed clonal repopulation in aged rhesus macaques and in mice.

  • 2a. Shihyoung Kim, Rajni Kant Shukla, Eunsoo Kim,Sophie G. Cressman, Hannah Yu, Alice Baek, Hyewon Choi, Alan Kim, Amit Sharma, Zhirui Wang, Christene A. Huang, John C. Reneau, Prosper N. Boyaka, Namal P. M. Liyanage, and Sanggu Kim* “Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular LeakageBiomedicines 2022, 10, 1221. https://doi.org/10.3390/biomedicines10061221
  • 2b. Shihyoung Kim, Alice Baek, Rajni Kant Shukla, Sophie G Cressman, Hannah Yu, Sarah Golconda, Hye Won Choi, John C Reneau, Zhirui Wang, Christene A. Huang, Namal P. M. Liyanage and Sanggu Kim*, “CD3e immunotoxin spares CD62Llo effector Tregs and reshapes organ-specific tissue-resident T-cell composition via preferential depletion of CD3ehi T cells.” Frontiers in Immunology, Accepted for publication. *Senior corresponding author

 

3. Development of systems biology and genomics tools for cell biology and virology

We develop various genomics tools to address challenging questions in retroviral pathogenesis and cellular gene therapy. We developed cellular barcoding assays and software for target quantitative sequencing, retroviral integration site assays and analysis software, and high-throughput HIV-1 genotyping and phenotyping assay.

  • 3a. Beihua Dong, Sanggu Kim, Seunghee Hong, Jaydip Das Gupta, Krishnamurthy Malathi, Eric A. Klein, Don Ganem, Joseph DeRisi, Samson A. Chow, Robert H. Silverman, “An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors”, 2007, Proceedings of the National Academy of Sciences. U S A.  104 (5) 1655-1660; PMID:17234809, PMCID:PMC1776164
  • 3b. Song Xu, Sanggu Kim, Irvin SY Chen, and Tom Chou, “Modeling large fluctuations of thousands of clones during hematopoiesis: the role of stem cell self-renewal and bursty progenitor dynamics in rhesus macaque,” 2018, PLoS Computational Biology, 14 (10): e1006489, PMID: 30335762
  • 3c. Gajendra W. Suryawanshi, Song Xu, Yiming Xie, Tom Chou, Namshin Kim, Irvin S.Y. Chen, and Sanggu Kim, “Bidirectional Retroviral Integration Site PCR Methodolgy and Quantitative Data Analysis Workflow”, 2017, Journal of Visualized Experiments, 14;(124). doi: 10.3791/55812., PMID: 28654067. Senior author