申请人结合干细胞和基因组编辑技术，研究人类衰老和衰老性疾病的分子机制和干预。在Nature (2),Science, Cell Stem Cell(2)和Nat Commun（2）等刊物发表论文69篇，包括通讯/共同通讯作者文章48篇。主持基金委重点和973等科研项目。研究成果：（1）利用iPSC技术阐明儿童早衰症血管退行的分子机理；（2）揭示帕金森病的神经干细胞病变，发现改善该病变的化合物；（3）利用HDAdV实现儿童早衰症iPSC致病突变靶向矫正；（4）证明HDAdV和TALEN基因靶向矫正工具安全性，发展高效基因矫正工具telHDAdV；（5）利用范可尼贫血症iPSC模型筛得改善造血干细胞活力的化合物；（6）发现异染色质高级结构失序是人干细胞衰老的驱动力；（7）建立人胶质母细胞瘤（GBM）的干细胞模型，筛得精准杀伤GBM干细胞的化合物；（8）揭示SIRT6调节人干细胞衰老的新机制。

Combining advanced stem cell and gene editing techniques, Dr. Guanghui Liu has made a series of high impact discoveries by studying mechanisms underlying human aging and aging-associated disorders. Dr. Liu has published 69 papers in prestigious peer-reviewed journals. In 48 publications he is the corresponding(or co-corresponding) author, including papers on Nature, Science, Cell Stem Cell, and Nat Commun. etc. Moreover,he has 8 patents, 3 of which are granted. From 2011 to 2016,Dr. Liu has made a serial of achievements in his field, including: (1)Established the first Hutchinson–Gilford progeria syndrome (HGPS) induced pluripotent stem cell (iPSC)disease model for studying molecular mechanisms underlying human vascular aging and atherosclerosis (Nature 2011);(2) Demonstrated the first time that the LRRK2(G2019S) gene mutation results in nuclear envelope defects and progressivede generation of human neural progenitor cells in Parkinson’s disease (PD), and discovered a LRRK2 protein inhibitor which can effectively rescue the neural stem cell pathology of PD (Nature 2012); (3)Corrected in situ for the first time a pathogenic mutation in patient-specific iPSCs using a helper-dependent adenovirial vector (HDAdV)-based approach (Cell Stem Cell 2011);(4) Proved for the first time that both HDAdV and well-designed TALEN are safe methods for targeting diseased human genome by whole genome sequencing. Also by combining HDAdV and TALEN techniques, developed a novel genome-editing tool named telHDAdV, which demonstrates a much higher gene targeting efficiency in human stem cells (Cell Stem Cell 2014);(5) Established for the first time a Fanconi Anemia disease model with isogenic and integration-free Fanconi Anemia patient iPSC lines, and demonstrated as a proof-of-principle that targeted gene correction and a small molecule application can improve the hematopoietic stem cell activity, and repress mesenchymal stem cell senescence in Fanconi Anemia (Nat Commun 2014); (6) Identified heterochromatin disorganization as a driver of human aging using a stem cell model of Werner Syndrome（Science 2015）;（7）Uncovered a potential mechanism of how tumor suppressor PTEN safeguards neural stem cells (NSCs), and establish a cellular platform to identify factors involved in NSC transformation, permitting personalized treatment of glioblastoma（Nat Commun 2015）;（8）Uncovered a novel function of SIRT6 in maintaining human mesenchymal stem cell homeostasis by serving as a NRF2 coactivator, which represents a new layer of regulation of oxidative stress-associated stem cell decay（Cell Res 2016）.