Speakers at ICG-13

Speakers at ICG-13

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Biography

Dr. Guanghui Liu is a professor at the Institute of Biophysics, Chinese Academy of Sciences. He aims to identify the mechanisms underlying human stem cell aging and their implications in human age-associated disorders. The mission of Dr. Liu’s laboratory is to establish a global view on the factors contributing to or antagonizing human stem cell aging, and to develop novel therapeutic interventions for the goal of “healthy aging”. His studies have demonstrated that (1) Heterochromatin alteration is a driver of human aging (Science 2015); (2) Dysregulated NRF2 pathway results in stem cell senescence (Cell 2016; Nature 2011; Cell Res 2016); (3) LRRK2 mutation leads to the degeneration of neural stem cells in Parkinson’s disease (Nature 2012); (4) Targeted gene correction improves the hematopoietic stem cell activity in Fanconi Anemia (Nat Commun 2014); (5) PTEN-deficiency reprograms human neural stem cells towards glioblastoma stem like cells (Nat Commun 2015); (6) both HDAdV and TALEN are safe methods for correcting diseased genome, and the telHDAdV (a novel HDAdV and TALEN combined technique) demonstrates a much higher gene-editing efficiency (Cell Stem Cell 2011/2014); (7) Eight disease mutations are successfully corrected by various gene editing tools; (8) A single nucleotide editing in NRF2 gene endow human stem cells with resistance to senescence and oncogenic transformation (Cell Res 2017); (9) Ribosomal DNA attrition acts as a novel biomarker of human aging (Cell Res 2017); (10) Oltipraz, Vitamin C, and Metformin are identified as geroprotective compounds with human stem cell aging models (Cell 2016; Aging Cell 2018). Dr. Liu has published over 80 publications in Nature, Science, Cell, etc. prestigious journals. Dr. Liu has been an active member of the international scientific community; he is the president of Chinese Society of Aging Cell Research (CSACR), and an Associate Editor of Stem Cell Research & Therapy, and Protein & Cell.    


Abstract

Using stem cell and gene editing techniques to study and treat aging-associated disorders

Guang-Hui Liu

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

 Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two human premature aging disorders with features that closely recapitulate the characteristics of human aging. Mutations in LMNA and WRN genes lead to aberrant splicing product progerin and protein loss in HGPS and WS, respectively. Study on how genetic alteration leads to the cellular and organismal phenotypes of premature aging will provide clues to the molecular mechanisms underlying physiological aging and facilitate our understanding of the molecular pathways contributing to healthy aging. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS, Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Fanconi Anemia (FA), and Xeroderma pigmentosum (XP). Further, using targeted gene correction technique, we successfully corrected the mutated LMNA in HGPS-iPSCs, mutated LRRK2 in PD-iPSCs, mutated FANCA in FA-iPSCs, and mutated SOD1 and FUS in ALS-iPSCs. Finally, by using targeted “knock-out” and “knock-in” techniques, we generated WS-, FA-, PD-, and Glioblastoma multiforme (GBM)-specific human stem cells with relevant pathogenic mutations. Upon differentiation of these disease-specific pluripotent stem cells to specific somatic cell types, the latter recapitulated aging/disease-associated and tissue-specific phenotypic defects. We also generated genetically enhanced stem cells (GES cells) which were resistant to cellular aging and oncogenic transformation by editing a single nucleotide in human genome. Altogether, these studies provide important platforms for studying aging/disease mechanisms and developing new therapies.

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