Low Boon Chuan

Principal Investigator, MBI

email: dbslowbc@nus.edu.sg

Associate Professor and Principal Investigator, Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore

To identify novel signaling proteins and protein domains that control cell morphogenesis, motility, differentiation and cell growth and tissue/organ development during normal and disease states. Areas of interest include cell signaling, domain-discovery, protein-protein interaction, structural biology, developmental biology, computational biology and mechanobiology.

Molecular recognition forms the basis for all cellular events- from a simple bimolecular enzymatic reaction to the cascades of multimeric protein complex in cell signaling. Fundamental to the structure and function of a protein is its ‘domain’- a discrete, minimal modular entity that constitutes one of the basic physical and functional unit of the polypeptide. This protein domain can either serve as a protein docking/interaction site or an active enzymatic unit. With the emphasis on functional genomics, it is important to address what role does each of these domains play and how their potential functions can be regulated across molecular, cellular and tissue levels.

One of the several protein domains that our group first identified and characterised is a novel protein domain termed BCH domain which play important roles in regulating cell growth/death, differentiation, migration, and tissue/organ development. Based on the prototypical BNIP-2 and BPGAP1 proteins, we show that distinct BCH domains could act as key modulators for Rho and Ras small GTPases as well as their immediate regulators such as guanine nucleotide exchange factors and GTPase-activating proteins. Current effort is geared towards understanding how cells and tissues respond to the dynamic forces and geometry in the environment both under the influence of the BCH domain. This will be addressed under the newly established MBI.

Assoc Prof Low left Kuala Lumpur, Malaysia for Dunedin, New Zealand in early 90’s to pursue his dream as a scientist. Having spent wonderful undergraduate and postgraduate years at the Department of Biochemistry, University of Otago, he joined IMCB, Singapore and then NUS, trying to figure out what exactly make cells work. Amazing as it is, we are still far from understanding the intricacy underlying these processes. Trained as a biochemist, practising mainly as a cell biologist now, and with exciting arrays of multi-disciplinary tools, his team and collaborators aim to systematically unravel some of the uncharted paths, and are ready to expect the unexpected.


Yi P, Chew LL, Zhang Z, Ren H, Zheng L, Luo Y, Ouyang H, Low BC, and Zhou YT. KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation. Mol Biol Cell, 2015 Jan 1;26(1):29-42.

Ravi A, Kausik S, Ravichandran A, Pan CQ, Low BC. Epidermal Growth Factor Activates the Rho GTPase-activating Protein (GAP) Deleted in Liver Cancer 1 via Focal Adhesion Kinase and Protein Phosphatase 2A. J Biol Chem, 2014, pii: jbc.M114.616839. [Epub ahead of print]

Kaushik A, Ravi A, Hameed FM, Low BC. Concerted Modulation of Paxillin Dynamics at Focal Adhesions by DLC1 and FAK during Early Cell Spreading. Cytoskeleton (Hoboken). 2014, doi: 10.1002/cm.21201. [Epub ahead of print]

Low BC, Pan CQ, Shivashankar GV, Bershadsky A, Sudol M, Sheetz M. YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and tumor growth. FEBS Lett. 2014, 588(16):2663-70.

Chew TW, Liu XJ, Liu L, Spitsbergen JM, Gong Z, Low BC. Crosstalk of Ras and Rho: activation of RhoA abates Kras-induced liver tumorigenesis in transgenic zebrafish models. Oncogene. 2014, 33(21):2717-27.

Thangavelu K, Chong QY, Low BC, Sivaraman J. Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA). Scientific Reports. 2014, 4:3827. doi: 10.1038/srep03827

Zhao C, Liu C, Hogue CW, Low BC. A cooperative jack model of random coil-to-elongation transition of the FH1 domain by profilin binding explains formin motor behaviour in actin polymerization FEBS Letters. 2014, 588(14):2288-93.

Bayat S, Brasseur A, Chua XL, Zhang Y, Zhou Q. Low BC and He CY. The bi-lobe-associated LRRP1 regulates Ran activity in Trypanosoma brucei. Journal of Cell Science. 2014, 127(22):4846-56.

Pan CQ and Low BC (2012) Functional plasticity of the BNIP-2 and Cdc42GAP Homology (BCH) domain in cell signaling and cell dynamics. FEBS Letters Vol. 586, Issue 17, Pages 2674-2691. Learn more.

*Thangavelu K, *Pan CQ, Karlberg T, Balaji G, Uttamchandani M, Suresh V, Schüler H, Low BC, Sivaraman J. (2012) Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc Natl Acad Sci U S A. 2012 Apr 26. [In Press] *co-first authors

Gupta AB, Wee LE, Zhou YT, Hortsch M, Low BC (2012) Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily. PLoS One. 2012;7(3):e33863

Zhu S, Low BC (2012) Using zebrafish for studying Rho GTPases signaling in vivo. Methods Mol Biol. 827:321-37

Huang L, Pan CQ, Li B, Tucker-Kellogg L, Tidor B, Chen Y, Low BC (2012) Simulating EGFR-ERK signaling control by scaffold proteins KSR and MP1 reveals differential ligand-sensitivity co-regulated by Cbl-CIN85 and endophilin.PLoS One. 2011;6(8):e22933

Zhou, Y.T, Chew, L.L, Lin, S.C, Low, B.C (2010) The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain. Mol Biol Cell. 2010 21(18):3232-46

Pan, Catherine Q., Liou, Y-C and Low, B.C (2010) Active Mek2 as a regulatory scaffold that promotes Pin1 binding to BPGAP1 to suppress BPGAP1-induced acute Erk activation and cell migration. J Cell Sci. 123(Pt 6):903-16

Zhong D, Zhang J, Yang S, Soh UJ, Buschdorf JP, Zhou YT, Yang D, Low BC (2009). The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration. J Cell Sci. 122(Pt 3):414-24

Kang, J-S., Bae, G-U., Yi, M-J., Yang, Y-J., Oh, J-E., Takaesu, G., Zhou, Y.T., Low, B.C., and Krauss, R.S. (2008) A Cdo/Bnip-2/Cdc42 signaling pathway regulates p38alpha/beta MAPK activity and myogenic differentiation. J. Cell Biol 182(3):497-507