Cell Signaling and Developmental Biology Laboratory
Department of Biological Science
National University of Singapore
14 Science Drive 4
Principal Investigator, MBI: weblink
Deputy Director, USP: Weblink6516 7834
2006-present - Associate Professor, Dept of Biological Sciences, National University of Singapore
2001-2005 - Assistant Professor, Dept of Biological Sciences, National University of Singapore
1999-2000 - Research Associate, Institute of Molecular and Cell Biology, Singapore
1995-1999 - Post-Doctoral Research Fellow, Institute of Molecular and Cell Biology, Singapore
1995-1995 - Assist. Lecturer /Junior Research Fellow, Dept of Biochemistry, University of Otago, New Zealand
2003- Singapore National Academy of Science-A*STAR Young Scientist Award
2003- NUS Faculty of Science Teaching Excellence Award
2003 - Who's Who in Science and Engineering (Marquis, 7th Edition)
2002 - A*STAR Biomedical Research Council (BMRC) Young Investigator Award
1995 - UNESCO Travel Fellowship for the 7th FAOBMB Congress (Sydney)
1995 - Postdoctoral Research Fellowship, Institute of Molecular and Cell Biology
1994 -University of Otago Centre for Gene Research Best Poster Award
1992 -1995 New Zealand Vice-Chancellors' Committee Scholar
1992 -1995 Malaysia/Singapore Lee Foundation Study Award
1992 -Best Poster Award in Queenstown International Molecular Biology Meeting
1992 -New Zealand Health Research Council Summer Scholarship
1991 -Edson Prize in Biochemistry, University of Otago
1990 -Proudfoot Award in Experimental Science, University of Otago
Cell Signaling, Developmental Biology and Mechanobiology.
To identify novel signaling proteins and protein domains that control cell growth and tissue/organ development in 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 characterized is a novel protein domain termed BCH domain (for BNIP-2 and Cdc42GAP Homology) 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 (GEFs) and GTPase-activating proteins (GAPs). 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 containing proteins and their associated GEFs or GAPs. This will be addressed under a newly established Research Centre of Excellence in Mechanobiology. To compliment this and to further link cell signalling events to developmental biology and pathophysiology, the zebrafish Danio rerio is used as the alternate animal model.
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, August 14, 2012 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 (link to story on MBI web)
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. 2012;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
Scott GB, Bowles PA, Wilson EB, Meade JL, Low BC, Davison A, Blair GE, Cook GP (2010) Identification of the BCL2/adenovirus E1B-19K protein-interacting protein 2 (BNIP-2) as a granzyme B target during human natural killer cell-mediated killing. Biochem J.431(3):423-31.
Ma XH, Shi Z, Tan C, Jiang Y, Go ML, Low BC, Chen YZ (2010) In-silico approaches to multi-target drug discovery : computer aided multi-target drug design, multi-target virtual screening. Pharm Res. 27(5):739-49. Review.
Kirilly D, Gu Y, Huang Y, Wu Z, Bashirullah A, Low BC, Kolodkin AL, Wang H, Yu F.A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning. Nat Neurosci.12(12):1497-505.
Li H, Ung CY, Ma XH, Li BW, Low BC, Cao ZW, Chen YZ (2009). Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1. Bioinformatics 1;25(3):358-64.
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.
Lu Z, Liu W, Huang H, He Y, Han Y, Wang Y, Li Q, Ruan K, Ye Z, Low BC, Meng A, Lin SC (2008) Protein encoded by the AxinFu allele effectively downregulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling. J Biol Chem. Mar 3; [Epub ahead of print]
Liu L.H., Zhu, S., Gong, Z.Y and Low, B.C (2008). K-ras/PI3K-Akt Signaling Is Essential for Zebrafish Hematopoiesis and Angiogenesis. PLoS ONE.3(8):e2850.
Buschdorf JP, Chew LL, Soh UJ, Liou YC, Low BC (2008). Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP-H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating neurons. PLoS ONE. 3(7):e2686.
Ma XH, Wang R, Yang SY, Li ZR, Xue Y, Wei YC, Low BC, Chen YZ (2008). Evaluation of virtual screening performance of support vector machines trained by sparsely distributed active compounds. J Chem Inf Model. 48(6):1227-37. Epub 2008 Jun 6.
Ung CY, Li H, Ma XH, Jia J, Li BW, Low BC, Chen YZ (2008). Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk. FEBS Lett. 582(15):2283-2290. Epub 2008 May 27.
Soh U.J and Low, B.C (2008) BNIP-2 Extra Long inhibits RhoA and cellular transformation by Lbc RhoGEF via its BCH domain. J. Cell Sci May 15;121(Pt 10):1739-49.
Zhu, S., Korzh, V., Gong, Z. and Low, B. C (2008) RhoA prevents apoptosis during zebrafish embryogenesis through activation of Mek/Erk pathway. Oncogene. 6;27(11):1580-9.
Lu Z, Liu W, Huang H, He Y, Han Y, Wang Y, Li Q, Ruan K, Ye Z, Low BC, Meng A, Lin SC (2008) Protein encoded by the AxinFu allele effectively downregulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling. J Biol Chem. May 9;283(19):13132-9
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
Tang ZQ, Han LY, Lin HH, Cui J, Jia J, Low BC, Li BW, Chen YZ. (2007) Derivation of stable microarray cancer-differentiating signatures using consensus scoring of multiple random sampling and gene-ranking consistency evaluation. Cancer Res.67(20):9996-10003.
Zhou,Y.T., Guy,G.R., Low, B.C. (2006) BNIP-Sa induces cell rounding during apoptosis by sequestering p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP Homology domain Oncogene 25(16):2393-408.
Buschdorf, J.P., Chew, L.L., Zhang, B., Cao, Q., Liang, F-Y., Liou, Y-C., Zhou, Y.T., Low, B.C (2006) Brain-specific BNIP-2-Homology (BNIP-H) protein/Caytaxin relocalizes glutaminase to neurite terminals and reduces the levels of glutamate. J. Cell Sci 119:3337-50
Zhu, S., Liu, L., Korzh, V., Gong, Z. and Low, B.C. (2006) RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho Kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cellular Signaling 18(3):359-372
Zhou,Y.T., Guy,G.R., Low, B.C. (2005) BNIP-2 induces cell elongation and membrane protrusions by interacting with Cdc42 via a unique Cdc42-binding motif within its BNIP-2 and Cdc42GAP homology domain. Exp. Cell Res., 303:263-274.
Lua, B.L. and Low, B.C. (2005) Activation of EGFR endocytosis and ERK1/2 activation by BPGAP1 requires its direct interaction with EEN/endophilin II and a functional RhoGAP domain. J. Cell Sci., 118: 2707-2721
Lua, B. L., and Low, B.C. (2005) Cortactin phosphorylation as a switch for actin cytoskeletal network and cell dynamics control. FEBS Letter (Review)579: 577-585.
Low, B C and Gong, Z. (2005) Reporter Gene System: Green Fluorescent Proteins. Encyclopedia. Mol. Cell Biol. and Mol. Med. Edited by Robert A. Meyers.
Zhang B, Cao Q, Guo A, Chu H, Chan YG, Buschdorf JP, Low BC, Ling EA, Liang F. (2005) Juxtanodin: an oligodendroglial protein that promotes cellular arborization and 2',3'-cyclic nucleotide-3'-phosphodiesterase trafficking. Proc Natl Acad Sci U S A. 102(32):11527-32.