Yanhong Shi, Ph.D.

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Yanhong Shi, Ph.D.
Professor and Chair, Department of Neurodegenerative Diseases, Director, Division of Stem Cell Biology Research
Research Area
  • Stem Cell Biology
  • Regenerative Medicine
  • Human IPSC-based Disease Modeling and Therapeutic Development
  • Aging
  • Alzheimer’s Disease, Canavan Disease, and Cancer
Academic Appointments
  • Chair, Department of Neurodegenerative Diseases
  • Herbert Horvitz Professor in Neuroscience
  • Director, Division of Stem Cell Biology Research
  • Director, Stem Cell Core
Research Teams
Neurodegenerative Diseases

Yanhong Shi, Ph.D, is the Chair of the Department of Neurodegenerative Diseases, Herbert Horvitz Endowed Professor in Neuroscience, and Director of the Division of Stem Cell Biology Research at the Beckman Research Institute of City of Hope®. Dr. Shi is also a beneficiary of the Christopher Family Endowed Innovation Fund for Alzheimer’s Disease Research in Honor of Vineta Christopher, and an elected fellow of the American Institute for Medical and Biological Engineering (AIMBE).

Dr. Shi has a longstanding interest in the induced pluripotent stem cell (iPSC) technology and its applications in disease modeling, drug discovery, and cell therapy. The Shi laboratory has pioneered innovative human iPSC-based models of Alzheimer’s disease (listen to a podcast here) and other neurological diseases (see here). Dr. Shi was a scientific organizer of the Keystone Symposia “iPSCs: A Decade of Progress and Beyond,” a landmark conference that set the trends for the next decade of iPSC technology-based research (see Shi et al. 2017). The Shi laboratory has also developed cGMP-compatible manufacturing processes for human iPSC derivation, differentiation, and genetic engineering, and has demonstrated robust disease-modifying effects of human iPSC-derived neural progenitor cells as a cell therapy for Canavan disease in preclinical studies (highlighted here).

Dr. Shi also aims to understand the molecular mechanisms that govern brain cancer progression with a focus on glioblastoma and RNA modifications. The Shi laboratory was among the first to demonstrate a therapeutically actionable dysregulation of RNA modifications in glioblastoma (Cui et al. 2017, Cui et al. 2021), thus uncovering a novel approach to treat brain cancer. Together with other experts in the field, Dr. Shi  is also part of the inaugural 2023 NSAS Summit workshops “Exploring the Brain Epitranscriptome” focused on RNA modifications in brain development and diseases to promote research into brain epitranscriptomics and facilitate RNA modification-targeted therapeutic development (see Lee et al., 2023).

Location

Education & Experience

Degrees

  • Ph.D., Northwestern University, Evanston, IL.

Fellowship

  • Postdoctoral Fellow, The Salk Institute, La Jolla, CA

Research

The Shi lab at Beckman Research Institute of City of Hope is focused on human induced pluripotent stem cell (iPSC)-based disease modeling, drug discovery, and cell therapy development for debilitating diseases, including Alzheimer’s disease, Canavan disease, and cancer. The Shi lab has developed cGMP-compatible manufacturing processes for human iPSC derivation, differentiation, and genetic engineering, has demonstrated robust disease-modifying effects of human iPSC-derived neural progenitor cells as a cell therapy for Canavan disease in preclinical studies, and is rigorously developing human iPSC-based disease models and cell therapies for Alzheimer’s disease and cancer. Dr. Shi holds multiple patents on human iPSC-based technologies or cellular products and has published rigorously on human iPSC-related studies.

Laboratory

Research Areas

  • Project 1: Human iPSC-based disease modeling and drug discovery
  • Project 2: Human iPSC-based cell therapy development
  • Project 3: Immunotherapy and tumor-immune interactions
  • Project 4: RNA modifications and cancer stem cells of glioblastoma

Lab Members

  • George Sun, Ph.D.
  • Peng Ye, M.D.
  • Fay (Jianfei) Chao, Ph.D.
  • Qi Cui, Ph.D.
  • Yue Qin, Ph.D.
  • Cheng Wang, Ph.D.
  • Tao Zhou, Ph.D.
  • Zhenqing (Crystal) Liu, Ph.D.
  • Jonas Cerneckis
  • Natasha Jackson, Ph.D.
  • Hongxia Cai, Ph.D.
  • Jia Li, Ph.D.
  • Ding Wang, Ph.D.
  • Negar Seyed, Ph.D.
  • Kusuma Suphakhong
  • Shunyu Yao
  • Chloe Centeno
  • Kayla Galo

Publications

  • Cerneckis J and Shi Y. 2023. Context matters: human PSC-derived microglia thrive in a humanized brain environment in vivo. Cell Stem Cell 30: 909-910. doi: 10.1016/j.stem.2023.05.013.
  • Liu Z, Chao J, Wang C, Sun G, Roeth D, Liu W, Chen X, Li L, Tian E, Feng L, Davtyan H, Blurton-Jones M, Kalkum M, and Shi Y. 2023. Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model. Cell Reports 42: 112841. doi: 10.1016/j.celrep.2023.112841. 
  • Feng L, Chao J, Ye P, Luong Q, Sun G, Liu W, Cui Q, Flores S, Jackson N, Shayento ANH, Sun G, Liu Z, Hu W, and Shi Y. 2023. Developing hypoimmunogenic human iPSC-derived oligodendrocyte progenitor cells as an off-the-shelf cell therapy for myelin disorders. Advanced Science 10: e2206910. doi: 10.1002/advs.202206910.
  • Cui Q, Yin K, Zhang X, Ye P, Chen X, Chao J, Meng H, Wei J, Daniel R, Li L, Qin Y, Sun, G, Zhang M, Klein J, Huynhle M, Wang C, Zhang L, Badie B, Kalkum M, He C, Yi C, and Shi Y. 2021. Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis. Nature Cancer 2: 932-949. doi: 10.1038/s43018-021-00238-0. Featured in Nature Cancer 2021: doi: 10.1038/s43018-021-00255-z, Cancer Discovery 2021: doi:  10.1158/2159-8290.CD-RW2021-123, and The Stem Cellar: https://bit.ly/3xVLxJf.
  • Chen X, Sun G, Tian E, Zhang M, Davtyan H, Beach T, Reiman EM, Blurton-Jones M, and Shi Y. 2021. Modeling Alzheimer’s disease using human iPSC-derived brain organoids. Advanced Science. 8: e2101462. doi: 10.1002/advs.202101462. Featured in the NIA Blog: https://www.nia.nih.gov/news/scientists-use-human-derived-brain-cells-develop-more-realistic-disease-dish-models-alzheimers, and The Stem Cellar: https://bit.ly/3yqxwVg.
  • Wang C, Zhang M, Garcia G, Tian E, Cui Q, Chen C, Sun, G, Wang J, Arumugaswami V, and Shi Y. 2021. ApoE isoform-dependent SARS-CoV-2 neurotropism and cellular response. Cell Stem Cell. 28: 331-342.e5. doi: 10.1016/j.stem.2020.12.018. Featured in ALZFORUM: https://www.alzforum.org/news/research-news/apoe-tied-increased-susceptibility-sars-cov-2, and The Stem Cellar: https://blog.cirm.ca.gov/2021/01/21/cirm-funded-researchers-discover-link-between-alzheimers-gene-and-covid-19/.
  • L Feng, Chao J, Tian E, Li L, Peng Y, Zhang M, Chen X, Cui Q, Sun G, Zhou T, Felix G, Qin Y, Meza ED, Klein J, Ghoda L, Hu W, Luo Y, Dang W, Hsu D, Gold J, Goldman SA, Matalon R, and Shi Y. 2020. Cell-based therapy for Canavan disease using human iPSC-derived NPCs and OPCs. Advanced Science 7: 2002155. doi: 10.1002/advs.202002155.
  • Li L, Tian E, Chen X, Chao J, Klein J, Qu Q, Sun G, Sun G, Huang Y, Warden CD, Ye P, Feng L, Li X, Cui Q, Sultan A, Douvaras P, Fossati V, Sanjana NE, Riggs AD, and Shi Y. 2018. GFAP mutations in astrocytes impair oligodendrocyte progenitor proliferation and myelination in a human iPSC model of Alexander disease. Cell Stem Cell 23: 239-251.
  • Cui Q, Shi H, Ye P, Li L, Qu Q, Sun G, Sun Gu, Lu Z, Huang Y, Yang C-G, Riggs A, He C, and Shi Y. 2017. M6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Reports 18: 2622-2634. 
  • Shi Y, Inoue H, Wu, JC, and Yamanaka S. 2017. Induced pluripotent stem cell technology: a decade of progress. Nature Reviews Drug Discovery 16: 115-130.

Link of additional publications from the Shi lab
www.pubmed.ncbi.nlm.nih.gov