Molecular Mechanisms of Ageing
Dr Liu, Baohua (劉宝華)
Research Assistant Professor, Department of Biochemistry
BSc (Peking University); PhD (The University of Hong Kong)
- Email: firstname.lastname@example.org
- Tel: (852) 2819 9169 (Lab)
- Office: L3-54, Laboratory Block, 21 Sassoon Road, Hong Kong
Ageing is a progressive deterioration of the physiological functions necessary for survival and fertility. Hutchinson-Gilford progeria syndrome (HGPS) is an early on-set progeroid disorder, predominantly caused by a de novo G608G mutation in LMNA gene. The G608G mutation activates a cryptic splicing site, yielding a partially processed prelamin A termed progerin (Eriksson et al., 2003). Progerin is also expressed at low level and accumulates during normal aging process in healthy individuals (Scaffidi and Misteli, 2006). Mice lacking Zmpste24, a metalloproteinase responsible for prelamin A maturation, recapitulate many progeroid features of HGPS (Pendas et al., 2002).
My research focus is on the molecular mechanisms underlying accelerated ageing and physiological ageing process. We and others have shown that HGPS skin fibroblasts and mouseembryonic fibroblasts (MEFs) derived from progeria mouse model undergo early senescence attributable to genomic instability and hyperactivation of the p53 pathway, and that reduction of the prelamin A level in progeria mice by Lmna heterozygosity ameliorates progeroid phenotypes and extends lifespan (Fong et al., 2004; Liu et al., 2005; Varela et al., 2005). Currently, we are investigating (1) the contribution of adult stem cell decline and somatic senescence to premature ageing in progeroid mouse model; (2) the potential links between HGPS and conserved longevity and ageing pathways, such as SIRT1 and TOR pathways; (3) epigenetic regulation of premature ageing and normal ageing process; and (4) therapeutic agents for the treatment of HGPS.
Publications, Achievements, and Grants:
- Liu B, Ghosh S, Yang S, Zheng H, Liu X, Wang Z, Jin G, Zheng B, Kennedy BK, Suh Y, Kaeberlein M, Tryggvason K, Zhou Z. Resveratrol rescues Sirt1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metabolism 2012, 16(6); 738-750
- Liu B, Wang Z, Ghosh S, Zhou Z. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model. Aging Cell 2012 (in press)
- Krishnan V, Liu B, Zhou Z. DNA repair in human diseases and aging. DNA repair. (Book chapter, in press).
- Krishnan V, Chow MZY, Wang Z, Zhang L, Liu B, Liu X, Zhou Z. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient progeria mice. PNAS 2011; 108(30):12325-30.
- Jin G, Zhang F, Chan KM, Wong HL, Liu B, Zhou Z, et al. MT1-MMP inhibits Notch signaling to maintain normal B cell development. EMBO Journal 2011; 30(11):2281-93.
- Liu B, Zhou Z. Lamin A/C, laminopathies and premature ageing. Histology and Histopathology 2008 Jun; 23(6):747-63.
- Krishnan V, Liu B, Zhou Z. Proficiency of DNA repair networks in stem cells as determinants of aging. Cell Science 2007.
- Liu B, Wang J, Chan KM, Zhou Z, et al. Genomic instability in laminopathy-based premature aging. Nature Medicine 2005; 11 (7):780-785.
- Zhou Z, Wang J, Cao R, Morita H, Soininen R, Chan KM, Liu B, Cao Y, Tryggvason K. Impaired angiogenesis, delayed wound healing and retarded tumor growth in Perlecan heparan sulfate deficient mice. Cancer Research 2004; 64(14):4699-4702.
- Zhou Z, Doi M, Wang J, Cao R, Liu B, Chan KM, Kortesmaa J, Sorokin L, Cao Y, Tryggvason K. Deletion in laminin α4 results in increased tumor angiogenesis and metastasis Cancer Research 2004; 64(12):4059-4063.
- Chen J, Liu B, Liu Y, Han Y, Yu H, Zhang Y, Lu L, Zhen Y, Hui R. A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated in failing heart. Biochem Biophys Res Commun. 2002; 294(1):161-6.
- Liu B, Liu Y, Chen J, Wei Z, Yu H, Zhen Y, Lu L, Hui R. CARP is a novel caspase recruitment domain containing pro-apoptotic protein. Biochem Biophys Res Commun. 2002; 293(5):1396-404.