Senior Research Fellow, MBI
Cell signaling, cell dynamics, cellular metabolism, mechanobiology, neurobiology and cancer biology
Signal transduction transmits molecular signals from extracellular to intracellular. The specificity is dependent on the molecular recognition during the signal transduction. Signaling proteins can utilize their unique protein domains architecture to exert their distinct cellular functions in space and time. In particularly, scaffold proteins that are multi-domain proteins, could act as a signaling hub for efficient and precise processing of cellular signals. Establishing key modular steps in the signaling network and protein functions in regulating cell morphogenesis, motility and tissue development are crucial for understanding both normal functions and patho-physiological diseases in order to provide potential therapeutic intervention.
Our laboratory focuses on cellular signaling linked to Rho and Ras small GTPases that are master switches for actin cytoskeleton, cell proliferation and differentiation respectively. These small GTPases can be regulated by their immediate regulators such as guanine nucleotide exchange factors (GEFs) and GTPases-activating proteins (GAPs). Current efforts are geared towards understanding how various scaffold proteins can modulate Rho and Ras small GTPases as well as their immediate regulators such as guanine nucleotide exchange factors (GEFs) and GTPases-activating proteins (GAPs). Perturbation of these signaling pathways are often linked to cancer, in particular metastasis which causes more than 90% of cancer deaths. Cancer metastasis is a multi-step migratory process that involve Rho GTPases to regulate actin remodeling for morphological changes and motility. We will address cell dynamics and actin remodeling by using high resolution microscopy, several in vitro (such as cancer cell transendothelial migration and cellular invasion assays) and in vivo (cancer metastasis in zebrafish Danio rerio model) model systems to elucidate the mechanical steps and functional roles of our proteins of interest in cancer biology.
Dr Catherine Pan joined MBI in 2012 as Senior Research Fellow. She received her PhD training in the Department of Biological Sciences, National University of Singapore in 2010 under the supervision of Prof Low Boon Chuan. Her PhD work involved understanding how the scaffold protein, BPGAP1 can regulate Ras signaling in cell migration. She went on to elucidate how BPGAP1 promotes ERK signaling for cell growth control and Rac signaling in cancer cell metastasis through the formation of lamellipodia. Her work involves extensive use of biochemical, molecular and cellular imaging tools as well as various cellular and animal models. She actively collaborates with clinicians and scientists both locally and overseas. She has won numerous international travel grant awards such as EMBO, ASCB, ASBMB and SEA-EU-NET’s International European Research Council Starting Grant Travel award. In addition, she was awarded the Journal of Cell Science (The Company of Biologists) travelling fellowship to undergo training at Prof Anne Ridley’s laboratory in King’s College of London. In 2014, she has won the National Medical Research Council (NMRC) CBRG-NIG (Cooperative Basic Research Grant-New Investigator Grant) to pursue her independent research.
Ramachandran S, Pan CQ, Zimmermann SC, Duvall B, Tsukamoto T, Low BC, and Sivaraman J. Structural basis for exploring the allosteric inhibition of human kidney type glutaminase. Oncotarget 2016;. [PMID: 27462863]
Chaudhuri PK, Pan CQ, Low BC, and Lim CT. Topography induces differential sensitivity on cancer cell proliferation via Rho-ROCK-Myosin contractility. Sci Rep 2016; 6:19672. [PMID: 26795068]
Sun J, Pan CQ, Chew TW, Liang F, Burmeister M, and Low BC. BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis. Dev. Cell 2015; 34(5):555-68. [PMID: 26343454]
Cui Y, Hameed FM, Yang B, Lee K, Pan CQ, Park S, and Sheetz M. Cyclic stretching of soft substrates induces spreading and growth. Nat Commun 2015; 6:6333. [PMID: 25704457]
Ravi A, Kaushik S, Ravichandran A, Pan CQ, and 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; 290(7):4149-62. [PMID: 25525271]
Low BC, Pan CQ, Shivashankar GV, Bershadsky A, Sudol M, and Sheetz M. YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and tumor growth. FEBS Lett. 2014; 588(16):2663-70. [PMID: 24747426]
Pan CQ, and Low BC. Functional plasticity of the BNIP-2 and Cdc42GAP Homology (BCH) domain in cell signaling and cell dynamics. FEBS Lett. 2012; 586(17):2674-91. [PMID: 22710163]