Education

1984, B.Sc. Xiamen University;

1991, Ph.D., UT Southwestern Medical Center at Dallas.

Professional Experience

1991-1995, Postdoctoral Fellow at the Howard Hughes Medical Institute, UCSD;

1995-2001, Principal Investigator, IMCB, Singapore;

2001-2006, Assistant Professor/Associate Professor (tenured), Hong Kong University of Science and Technology;

2003-2017, Dean, School of Life Sciences, Xiamen University;

2006 to PresentPresent, Professor, Cheung Kong Scholar, Xiamen University.

Member of CAS, 2021.

Research Area

Our research lies in the broad area of the molecular mechanisms that underlie metabolic homeostasis and its relationship to cell growth control. We have discovered a signaling pathway comprising the protein kinase GSK3, acetyltransferase TIP60, and protein kinase ULK1, which activates autophagy in cells deprived of serum, elucidating the molecular mechanism linking nutritional starvation to autophagy. We have also revealed that the ULK kinases phosphorylate multiple glycolytic enzymes and regulate glucose metabolic fluxes dependently of autophagy. The main focus of our research has also been on the mechanisms for the regulation of the AMP-activated protein kinase. We have shown that the lowenergy signal AMP can autonomously initiate assembly of an activating complex for the energy sensor kinase AMPK, in that the scaffold protein AXIN tethers LKB1 to AMPK. Moreover, we have found that the AXIN/LKB1/AMPK complex and mTORC1 inversely utilize the common v-ATPaseRagulator complex for activation on the surface of lysosome, thereby uncovering a switch between anabolism and catabolism. We are exploring further how AMPK and its activating kinase LKB1 are regulated and the biological functions of these kinases.

Selected Publications

1.Ma T, Tian X, Zhang BD, Li MQ, Wang Y, Yang CY, Wu JF, Wei XY, Qu Q, Yu YX, Long ST, Feng JW, Li C, Zhang, CX, Xie CC, Wu YU, Xu ZN, Chen JJ, Yu Y, Huang X, He Y, Yao LM, Zhang L, Zhu, MX, Wang W, Wang ZC, Zhang ML, Bao YQ, Jia WP, Lin SY, Ye ZY, Piao HL, Deng XM^*, Zhang CS^*, Lin SC^*. Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature, 603(7899)(2022), 159-165.
2.Shi M, Huang XY, Ren XY, Wei XY, Ma Y, Lin ZZ, Liu DT, Song L, Zhao TJ, Li G, Yao L, Zhu M, Zhang C, Xie C, Wu Y, Wu HM, Fan LP, Ou J, Zhan YH, Lin SY^*, Lin SC^*. AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1. Nat Cell Biol. 23(3)(2021), 268-277.
3.Zong Y, Zhang CS, Li M, Wang W, Wang Z, Hawley SA, Ma T, Feng JW, Tian X, Qi Q, Wu YQ, Zhang C, Ye Z, Lin SY, Piao HL, Hardie DG, Lin SC^*. Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress. Cell Research, 29(6)(2019), 460-473.  
4.Li M, Zhang CS, Zong Y, Feng JW, Ma T, Hu M, Lin Z, Li X, Xie C, Wu Y, Jiang D, Li Y, Zhang C, Tian X, Wang W, Yang Y, Chen J, Cui J, Wu YQ, Chen X, Liu QF, Wu J, Lin SY, Ye Z, Liu Y, Piao HL, Yu L, Zhou Z, Xie XS, Hardie DG, Lin SC^*. Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK. Cell Metabolism, 30(3)(2019), 508-524.
5.Luo H, Jiang M, Lian G, Liu Q, Shi M, Li TY, Song L, Ye J, He Y, Yao L, Zhang C, Lin ZZ, Zhang CS, Zhao TJ, Jia WP, Li P, Lin SY^*, Lin SC^*. AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity. Cell Metabolism, 27(4)(2018), 843-853.
6.Zhang CS, Hawley SA, Zong Y, Li MQ, Wang ZC, Gray A, Ma T, Cui JW, Feng JW, Zhu MJ, Wu YQ, Li TY, Ye Z, Lin SY, Yin HY, Piao HL, Hardie DG^*, Lin SC^*. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature, 548(7665)(2017), 112-116.
7.Zhang CS, Li MQ, Ma T, Zong Y, Cui JW, Feng JW, Wu YQ, Lin SY, Lin SC^*. Metformin Activates AMPK through the Lysosomal Pathway. Cell Metabolism, 24(4)(2016), 521-522.
8.Zhang CS, Jiang B, Li MQ, Zhu MJ, Peng YY, Zhang YL, Wu YQ, Li TY, Liang Y, Lu ZL, Lian GL, Liu Q, Guo HL,Yin ZY, Ye ZY, Han J, Wu JW, Yin HY, Lin SY, Lin SC^*. The Lysosomal v-ATPase-Ragulator Complex is a Common Activator for AMPK and mTORC1, acting as a Switch between Catabolism and Anabolism. Cell Metabolism, 20(3)(2014), 526-540.
9.Zhang YL, Guo HL, Zhang CS, Lin SY, Li P, Wu JW, Lin SC^*. AMP as a low energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. Cell Metabolism, 18(4)(2013), 546-555.
10.Lin SY, Li TY, Liu Q, Zhang CS, Li X, Chen Y, Zhang SM, Lian GL, Liu Q, Ruan K, Wang Z, Zhang CS, Chien KY, Wu J, Li QX, Han JH, Lin SC^*. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science, 336(6080)(2012), 477-481.